Preparation of Three-Month Depot Injectable Microspheres of Leuprorelin Acetate Using Biodegradable Polymers

To obtain a three-month release injection of leuprorelin acetate, microspheres were prepared with copoly(DL-lactic/glycolic acid) or poly(DL-lactic acid) (PLA) using an in-water drying method, and drug release was evaluated. The content of water-soluble oligomers in the polymers was found to strongly affect the initial burst, and reducing the content to less than 0.1% was necessary to keep the first-day release below 10%. Drug loading of more than 15% also increased the initial drug release; the acceptable maximum loading was 12%. Elevation of the glass transition temperature of the microspheres was observed with an increase in drug loading. This suggests formation of a rigid structure, possibly with arrangement of the polymer around the drug cores like in a micelle. This structure provides a hydrophobic barrier against diffusion of the hydrophilic peptide, resulting in high trapping efficiency and long-term sustained release dependent on polymer erosion. The microspheres prepared with PLA having a m.w. of 12,000 to 18,000 provided linear sustained release and persistent serum levels of the drug in rats for over 3 months.     

Antitumor Effect of Arterial Administration of a Medium-Chain Triglyceride Solution of an Angiogenesis Inhibitor,TNP-470, in Rabbits Bearing VX-2 Carcinoma

Using rabbits bearing VX-2 carcinoma on the inner side of the leg, we examined the antitumor activity of a medium-chain triglyceride (MCT) solution of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-O-(N-chloroacetylcarbamoyl)-fumagillol), following administration into the femoral artery feeding the tumor. The MCT solution of TNP-470 (1 and 5 mg) strongly suppressed tumor growth following a single intra-arterial (i. a.) injection 2 or 3 weeks after tumor inoculation. Moreover, remarkable regression of well-developed tumors, those 4 weeks after inoculation, was obtained by i.a. injection of the MCT solution containing 20 mg of TNP-470 without any influence on body weight. The antitumor effects were potentiated by coad-ministration of doxorubicin or mitomycin C (MMC) in the solution or microspheres containing MMC. In a shell-less chorioallantoic membrane (CAM) assay, angiogenesis was inhibited when a droplet of the MCT solution containing 25 µg of TNP-470 was placed on the CAM for 2 days, suggesting that the prolonged antitumor effect resulted from the inhibition of tumor neovascularization by sustained drug release from the preparation. These results indicate that i. a. injection of the MCT solution of TNP-470 is promising for treating well-developed tumors.     

Method for home parenteral nutrition (HPN) at Daikou Sunadabashi Clinic

In recent years many patients who have become heavily dependent on medical care live at home. At Daikou Sunadabashi Clinic, we take care of many patients who have malignant tumors, at their homes. They need many medical treatments, so HPN has become a common practice. Here we show our circumstances of HPN. And we introduce our method for HPN. Our method is as follows: 1. Before the patient is discharged from the hospital, we go to the hospital and confirm the patient's condition. 2. We assess the level of training regarding HPN, and select the best way (instruments, circuits, administration) in consideration of the patients' or their families ADL. 3. We select a visiting nurse station 4. and train the visiting nurse in HPN using our manuals. 5. We use an HPN pump. 6. We select a simple way of infusion and adjust it to the patient's condition. In this way, we use HPN easily at home with the aid of a visiting nurse, visiting pharmacist, families, and us.     

Comparison of direct effects of clinically available vasodilators; nitroglycerin,nifedipine, cilnidipine and diltiazem,on human skeletonized internal mammary harvested with ultrasonic scalpel

Direct vasodilator effects of nitroglycerin, nifedipine, cilnidipine and diltiazem on human skeletonized internal mammary artery graft harvested with ultrasonic scalpel were assessed in the presence of 0.1 or 0.2 µM of noradrenaline. Ring preparations were made of distal end section of the bypass grafts, and those dilated by acetylcholine were used for assessment. Each drug dilated the artery in a concentration-related manner (0.01–10 µM, n = 6 for each drug) with a potency of nitroglycerin > nifedipine = cilnidipine > diltiazem. These results indicate that nitroglycerin can be useful for treating internal mammary artery spasm, that clinical utility of diltiazem may not depend on its vasodilator effect on the bypass graft, and that cilnidipine as well as nifedipine will have anti-spastic action which is in the middle between those of nitroglycerine and diltiazem.