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The lubricant property of sucrose esters of fatty acids (SEs) having different particle size and Hydrophile-Lipophile Balance (HLB) was evaluated with a model formulation in tableting. The binding tendency of the model formulation composed of isomalt powder was depressed by adding SEs in the formulation. Tablets containing SE showed faster disintegration time compared to those containing magnesium stearate or calcium stearate, while the tablets containing SEs indicated a high tensile strength. Milled SE (S-370F) exhibited better tablet properties than original SE (S-370). The SEs having different HLB showed different effects on the resultant tablet properties such as the magnitude of tensile strength, disintegration time, and spreading properties. The relatively hydrophilic SE was found to much improve the resultant disintegrating properties of tablet compared to magnesium stearate, calcium stearate and hydrophobic SEs. Consequently, SEs are able to use as lubricants on tablet formulation by appropriately controlling its particle size, content, and HLB.

Fast-disintegrating tablets of furosemide (FS) were prepared by the novel direct compression method. FS, microcrystalline cellulose (MC), croscarmellose sodium (CC), xylitol (XL) and sucrose stearic acid esters (SSEs) with an hydrophilic-lipophilic balance (HLB) of 16, 15 and 11, named S1670, S1570 and S1170, were used. An FS/SSE/MC mixed powder was obtained by solvent evaporation of a suspension of MC in ethanol solution containing FS and SSE, and the resultant mixed powder was mixed with CC and XL, and directly compressed. The tablets with hardness of more than 40 N and disintegration time of less than 20 s were obtained at the addition of SSE at 0--0.5% (w/w). A tablet with S1670 at 0.1% (w/w), named TA2, dissolved faster than a commercial FS tablet, Lasix. TA2 tended to show higher plasma concentration than Lasix after intragastric administration to rats. It was demonstrated that the present direct compression using homogeneous FS/S1670/MC powder mixture could give an excellent fast-disintegrating tablet of FS.

本研究は, 顎下腺の主導管結紮後と解除後における腺房細胞と筋上皮細胞の組織学的変化と再生過程を明らかにする目的で行われた. ラット顎下腺の主導管を1週間結紮し, その組織学的変化, 次いで結紮解除後の経日的変化を調べた. 免疫染色やTUNEL染色を施した試料について光学顕微鏡と透過電子顕微鏡による観察を行った.正常なラット顎下腺では, 筋上皮細胞に被われた導管様構造物は認められなかったが, 主導管結紮後, このような組織像が多数観察された. 光顕下では, アポトーシスを思わせるTUNEL染色陽性腺房細胞が若干観察されたが, 電顕観察では確認できなかった. このことから, 細胞死が生じたとしても少数であると思われた. 結紮解除後4週で顎下腺全体にほぼ正常な腺房が観察された. これらの所見から, 腺房の回復は主として導管様構造物が腺房へ回復することによるものと思われた.

A hydroxylated metabolite (5a) of 7-hydroxy-1-[[[4-(3-methoxyphenyl)-1-piperazinyl]acetyl]amino]-2,2,4,6-tetramethylindan (OPC-14117), which is a novel cerebroprotective agent with central nervous system-stimulating activity, was synthesized by use of a model cytochrome P-450 system. In order to confirm the structure of this compound it was prepared by another route. Tile structures of several metabolites (5a, 7 and 8) were identified by means of comparisons with the synthetic compounds.

Grepafloxacin (1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl )-4-oxo-3-quinoline-carboxylic acid, OPC-17116) (1) exhibits potent and broad-spectrum in vitro and in vivo antibacterial activity. In order to identify the structures of the metabolites of grepafloxacin, 17 possible metabolites were prepared. Among them, 6 compounds were found to be actual metabolites (2a, b, 4a, b and 6a, b) of grepafloxacin in rats, dogs and/or humans. The antibacterial activities of these metabolites were found to be weaker than that of grepafloxacin.

A novel series of N-acylamino acid analogues of 2 (1H) -quinolinone was synthesized and evaluated for antiulcer activity against acetic acid-induced gastric ulcer in rats. Out of this investigation, 2- (4-chlorobenzoylamino) -3- [2 (1H) -quinolinon-4-yl] propionic acid (rebamipide, OPC-12759) was identified The structureactivity relationships are discussed.Rebamipide did not only increase the healing rate of a chronic gastric ulcer model, acetic acid-induced gastric ulcer in rats, but also prevented recurrence and/or relapse of the ulcer in long term observation Rebamipide inhibited the formation of gastric mucosal lesions induced by various conditions. Rebamipide did not inhibit gastric acid secretion, although it potentiated gastric mucosal defensive factors such as mucus secretion, alkaline secretion, gastric mucosal blood flow and mucosal barrier. Rebamipide inhibited ethanol-induced gastric mucosal necrosis, which was completely abolished by pretreatment with indomethacin, suggesting the mucosal protective effect is associated with endogenous prostaglandins. Rebamipide inhibited production of superoxide from polymorphonuclear leukocytes and scavenged hydroxyl radical in vitro. Rebamipide showed useful efficacy on Helicobacter pylori-induced cell damage associated with activated neutrophils.The enantiomers of rebamipide were synthesized by using three efficient methods. Both enantiomers showed anti-ulcer activity against acetic acid-induced gastric ulcer and EtOH-induced gastric ulcer. The pair of enantiomers showed a small difference in activity.

An automatic fatigue crack tracking system with an image processor has been newly developed. This system consists of a microscope with a CCD camera, an image processor, a position measuring system, an automatic stage which moves the microscope, a personal computer and a fatigue testing machine. The tracking procedures fall into the following four distinct steps. Step 1 : When a maximum load is applied to the cracked specimen, the system obtains the image around the crack tip and stores the image to the frame memory. Step 2 : After appropriate stress cycles, the system obtains the image at the same position again. Step 3 : The image processor freezes the motion and subtracts the stored image from the image obtained in Step 2. Then the subtracted image is emphasized by adding the offset brightness level. Step 4 : The dark image which is obtained by preceding procedures, is tracked with a template by the position measuring system. The amount of shift of the template represents the length of fatigue crack extension. The system moves the microscope by a distance equal to the length of the crack extension. We applied this system to the fatigue crack propagation tests on steel and Si3N4 ceramics, and confirmed the reliability of our data.

The enantiomers of 7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolinone [(±)-1, flosequinan], a new drug for the treatment of heart failure, were synthesized from the optically active (R)-α-methylbenzylamine derivatives of quinoline. The key intermediates, (R)-α-methylbenzylamine derivatives, were prepared by diastereomeric separation. The configuration of (+)-1 was assigned on the basis of an X-ray crystallographic analysis of the synthetic precursor (4a). The absolute configuration was found to be (R)-(+)-1 and (S)-(-)-1.

We describe a rare case of sialolipoma of the palate. A 75-year-old Japanese man was referred because of a palatal mass, which measured 1.2×1.2 cm and was soft and painless. The mass had first been noticed 3 years previously and thereafter had slowly increased in size. It was removed for a clinical diagnosis of pleomorphic adenoma. The entire surgical specimen was processed for microscopic examination. Histologically, the tumor was well demarcated. It showed an admixture of adipose cells and glandular components and was traversed by delicate fibrous septa. The glandular component consisted of elongated tubules and some acinar cells. No cartilage or bone was observed. The tumor was diagnosed to be a sialolipoma. Sialolipomas are newly categorized uncommon tumors of the salivary gland, comprising an intimate admixture of mature fat cells and glandular elements. The tumor is well-circumscribed. Although few cases have been reported, sialolipoma tends to occur in the major salivary glands. Only a few palatal cases of sialolipoma have been reported. The patient is presently doing well 21 months after undergoing the operation.

Salivary duct cysts are acquired cysts that are believed to develop from marked cystic dilation of a salivary gland duct.The majority occur in the parotid gland, followed by the submandibular gland, and various other salivary glands. Here we report a case of salivary duct cyst of the tongue, together with a review of the literature. A 68-year-old woman was referred to us because of swelling of the tongue.On examination, a lesion measuring about 30×30mm was found at the front of the tongue.When palpated, the lesion was soft and slightly tender.The clinical diagnosis was a cystic lesion.The cyst was totally extirpated with the patient under general anesthesia.The histopathological diagnosis was a salivary duct cyst.This case apparently arose from the anterior lingual gland.