Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
6 巻, 2 号
選択された号の論文の10件中1~10を表示しています
  • 横山 昌幸, 岡野 光夫, 桜井 靖久, 片岡 一則
    1991 年 6 巻 2 号 p. 77-81
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    Concept and methodology of micelle-forming polymeric drug is reviewed. Drug targeting using drug carriers had been studied with three types of carriers ; liposomes, microspheres, and polymers. Now however, a successful example of drug targeting using any drug carrier has not been obtained because of low performance of drug carriers. A novel type of drug carrier system, micelle-forming polymeric drug is presented here. Polymeric micelles were constructed by amphiphilic structure of drug-polymer conjugate using a block copolymer, Expected superior features of the polymeric micelles as a drug carrier are long half-life in bloodstream, high water solubility, no long term-accumulation, high stability etc. Furthermore, functions which are needed for the ideal drug carrier can be shared by different polymer segments which become outer shell and inner core of the micelle. This separated functionality is favorable to get highly functionalized drug carrier system. Several unique characters and superior performance of the micelle-forming polymeric drug to the conventional drug carrier systems are described by the authors' work which is a conjugate of anticancer drug, adriamycin and poly(ethylene glycol)-poly(aspartic acid)block copolymer.
  • 今井 輝子, 福原 彰, 小田切 優樹, 植田 育男
    1991 年 6 巻 2 号 p. 83-87
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    The antiinflammatory effect, gastrotoxicity and in vivo absorption property of chimera drug of flurbiprofen(FP)with histamine H2-antagonist, PPA, were compared with those of FP and FP methyl ester. FP-PPA chimera drug and FP methyl ester were little hydrolyzed in the buffer of the pH 1.2 to 7.4 region in the absence or presence of pepsin and trypsin, in contrast to fast hydrolysis(t1/2 : about 20 sec)in rat plasma. FP chimera drug inhibited carrageenin induced paw swelling in the same level as FP alone. FP-PPA chimera drug significantly reduced gastrotoxicity in comparison to equivalent dose of FP, whereas the coad-ministration of FP with PPA did not affect gastrotoxicity of FP. FP methyl ester caused slightly less damage to the gastric mucosa than FP alone. The plasma concentration of FP after administration of FP derivatives were similar to FP alone. These data suggested that chimera drug is effective for reduction of gastric damage, compared with either FP or alkyl ester prodrug like methyl ester.
  • ―基礎実験―
    山田 明, 藤巻 雅夫, 上野 雅晴
    1991 年 6 巻 2 号 p. 89-96
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    The purpose of this experimental study is to analyze the efficacy of W/O/W type lipiodol emulsion containing peplomycin for the targeting therapy of regional lymph node metastasis of the esophageal cancer. The emulsion was newly perpared with two separated steps of emulsification, and it was appropriate for enhancement of an affinity to lymphatics. The emulsion containing peplomycin (10-20 mg) was endoscopically injected into the submucosal layer of the intrathoracic middle esophagus of the canines. Seven days after the injection, canines were sacrified, and the esophagus and intrathoracic lymph nodes along with other organs were resected. The retention of the emulsion was detected by X-ray examination, and the emulsion was only observed in the esophagus and some of regional lymph nodes. PEP concentration in the esophagus with detection of the emulsion (32.12±11.38 μg/g wet tissue in average)was much higher than the other organs. PEP concentration of regional lymph nodes with retention (7.76±3.32 μg/g in average) was higher than that in lymph nodes without detection of the emulsion (0.64±0.64 μg/g in average). Therefore the emulsion was appropriate for bringing about slow drug release. These results indicated that this emulsion might be useful for the targeting therapy for lymph node metastasis of the esophageal cancer.
  • 加藤 仁, 市田 隆文, 三浦 雅彦, 中郡 英次, 佐藤 博, 早川 晃史, 畑 耕次郎, 朝倉 均, 丹野 慶紀
    1991 年 6 巻 2 号 p. 97-101
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    To obtain a more possible effect against hepatocellular carcinoma (HCC), and gradually-releasing of cisplatin and epirubicin, we have tried to develop a new cisplatin-epirubicin-lipiodol suspension (CELS), using phosphatidylcholine as a coupling agent. Cisplatin and epirubicin were gradually released from CELS in vitro and passed gradually into systemic circulation after injection hepatic artery in vivo. Ten patients with HCC were treated with CELS therapy. Immediately, serum alpha-fetoprotein (AFP) and abnormal prothrornbin (PIVKA-II) levels were decreased. On most of 10 patients, no fatal side effects were observed. No survival ratio was estimated because of short term prognosis. It seems that the combination therapy with transcatheter arterial embolization (TAE) was more effective. This result suggests that CELS accumulates in the carcinoma tissue, and gradually releases the two drugs. It concludes that GELS therapy in safe and more effective compared with cisplatin suspended in lipiodol therapy for HCC.
  • 山村 恵子, 趙 学洙, 岩田 久
    1991 年 6 巻 2 号 p. 103-107
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    Hydroxyapatite (HAP) has been used recently in orthopaedic fields as an aid in bone grafts following surgery of bone tumors and bony defect at the time of revision surgery, often promoting osteoconduction as a result. It seems reasonable to incorporate antibiotics into porous HAP beads to prevent local infection. This report describes in vitro and in vivo release behavior of cefotiam (CTM, 3.5 mg/bead) lcaded into HAP beads (9.3 mm in diameter). To control release rate of CTM, egg phosphatidylcholine (EPC) was also incorporated into the beads with the drug. Drug release from EPC-free HAP beads attained 100% in 3h in vitro, and with increasing EPC incorporated the release rate was sustained. In vivo study where the beads were implanted into rat femur muscle, the drug from EPC-free HAP beads was released almost 100% in 7h and the EPC incorporated bead gave an extended release. The release behavior of CTM in vivo study was compatible with temporal courses of serum level following implantation of beads. We conclude that EPC can be useful in controlling the release rate of the drug from HAP beads.
  • 星 正彦, 阿部 郁夫, 杉山 克郎, 石塚 圭一, 佐藤 春彦, 漆山 昌伸, 涌井 昭
    1991 年 6 巻 2 号 p. 109-116
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    Comparison of the image intensity after injection of contrast media using dynamic computed tomography (CT) technique was carried out between angiotensin II human (TY-10721) induced hypertension (HT) and normotensive (NT) state in the patients with various metastatic liver tumor. Serial scanning time after 50 ml/10 sec of bolus injection of the contrast media (Iopamidol) was 0, 10, 30, 45, 60, 90 sec, 2, 3, 5, 8, 10, 15 min and each scan time was 4.5 sec. The relative ratio of each CT number in the ROI (region of interest) were calculated as the values before the injection of contrast media was estimated at 100%. The ratio of the peak CT numbers (HT/NT) was 115.9±15.7 (mean±SD) in tumor areas, and 89.8±21.6 in the normal liver, 94.6±10.2 in the muscle, 104.1±12.4 in the bone and 133.8±42.6 in the abdominal aorta. Moreover, in a comparison of AUC ratio between HT and NT during 0 to 10 minutes after the injection, in tumor areas it was 164.2±78.9, but in other normal tissues those were 60.4±45.7 (liver), 41.9±32.3 (muscle), 57.0±44.1 (bene) and 86.8±20.8 (aorta), respectively. The ratios of the peak and AUC between HT/ NT were significantly increased in only tumor areas (t-test ; P<0.001), though in all the other normal tissues, those were reduced. In a series of experiments and clinical results, selective increase of blood flow in the tumor tissues and significant increase of clinical effects were observed under TY-10721 induced HT. In addition to these evidences, this trial could show that selective enhancement of the medium delivery to tumor tissues was also obtained in the cancer patients.
  • 葛谷 昌之, 野口 章公, 伊藤 英樹, 石川 正直
    1991 年 6 巻 2 号 p. 119-125
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    As part of our continuing work on plasma chemistry and its application for the preparation of new pharmaceutically useful materials, we have examined preparations of multilayered particles applicable for DDS by use of plasma processing, and found that controlled-release tablet can be obtained by oxygen plasma irradiation (radio-frequency discharges operating at 13.56 MHz) on the outermost layer of the double-compressed tablet which were fabricated from theophylline tablet as a core material and a mixture of plasma-degradable polyoxymethylene (POM) and plasma-crosslinkable-polystyrene (PST) as a wall material. Dissolution test clearly indicated that the theophylline has been released from the tablet through the resulting micropore, whilst the release from untreated tablets was negligible. It was also found that dissolution profiles of theophylline can readily be controlled by the selection of a variety of factors for tablet fabrications as well as plasma operational conditions. One of the advantages of the present method over other methods is the avoidance of direct plasmaexposure to the drug.
  • 棟近 公司, 中江 孝, 菊川 彰人, 上田 泰生, 山内 紘一, 横山 和正, 塚越 茂
    1991 年 6 巻 2 号 p. 127-131
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    The modification of adriamycin(ADM)with oxidized dextran (OXD) make it possible to obtain high local concentration of ADM in the tumors. The intracellular behavior of ADM-OXD was studied to elucidate the mechanism of the cytotoxic action. Intracellular distribution of ADM was detected by fluorescence microscopy. The fluorescence of the cells treated with ADM-OXD was detected mainly in the cytosol 30min after treatment, and then it was shifted to the nuclei 6 hrs after treatment. On the other hand the fluorescece of the cells treated with ADM was detected mainly in the nuclei 30 min after treatment. [14C] ADM-OXD was prepared using 14C-ADM and the cell lysate following [14C] ADM-OXD treatment was subjected to GPC. The radioactivities were eluted at low molecular fraction which was similar to the case of ADM treatment. However, this shift to low molecular fraction was not observed by the addition of NH4Cl in the medium. Adriamycin-oxidized dextran conjugate prepared by amide bond which is stable under acidic condition had very low cytotoxic activity as compared with ADM-OXD, prepared by Schiff's base, which had a characteristics to release ADM under acidic condition. These findings suggested that ADM-OXD was uptaked into cells in the conjugated form and then ADM was released from ADM-OXD in the cells.
  • 藤田 浩, 岡本 公彰, 高尾 亜由子
    1991 年 6 巻 2 号 p. 133-138
    発行日: 1991/03/10
    公開日: 2009/02/23
    ジャーナル フリー
    Pharmacokinetics of ADM-OXD were studied by HPLC method in rabbits and Sarcoma 180 bearing mice and compared with those of ADM. (1) The plasma level of ADM-OXD was high and persisted for a long time. The drug level in the blood cells was lower than that in the plasma. (2) The tissue level of ADM-OXD was not so high in an early time after administration, but remained for several days. ADM-OXD distributed highly in tumor tissues as compared with ADM administered mice. ADM-OXD liberated free ADM in normal and tumor tissues. (3) ADM-OXD was excreted predominantly into the urine. (4) The liver-injured mice treated with CCl4 showed analogous drug level in the plasma and tumors, while lower level in the liver, as compared with control mice.
  • 1991 年 6 巻 2 号 p. 140
    発行日: 1991年
    公開日: 2009/02/23
    ジャーナル フリー
    本誌6巻1号review article“DDSの臨床応用への展望と問題点”中表2“市販ニトログリセリン貼付剤の比較”(p6)にミリスロール®テープの製造・販売元がトーアエイヨー・山之内とありますが,正しくはニチバン・日本化薬ですので,ここに報告申し上げます. (誤)トーアエイヨー・山之内 (正)ニチバン・日本化薬
feedback
Top