Masako Kajihara

Development of a new drug delivery system for protein drugs using silicone (II)

In order to achieve a zero-order release of protein drugs, we have developed a new drug delivery system using silicone, which is named the covered-rod-type formulation. Preparation of the covered-rod-type formulation was conducted under mild conditions without heat treatment or the use of organic solvents. The covered-rod-type formulation released human serum albumin (HSA) or interferon (IFN) at a constant rate for 30-100 days in vitro without significant initial burst. When the IFN covered-rod-type formulation was implanted in nude mice, the serum IFN concentration was maintained at a constant level during the period of observation, i.e., 28 days. The covered-rod-type formulation enabled precise control of the release of the protein drugs and would be expected to increase the duration of the drug effect and to reduce the frequency of administration and side effects.

Sustained release of human growth hormone (hGH) from collagen film and evaluation of effect on wound healing in db/db mice

Collagen films containing human growth hormone (hGH) were prepared and the release of hGH from these films and their effect on healing of full-thickness wounds in db/db mice were evaluated. The release profiles of hGH from the collagen films varied with composition and preparation conditions. The film prepared by air-drying of the mixture of hGH and collagen solution released hGH continuously over 3 days both in vitro and in vivo. By application of collagen film containing 3 mg of hGH twice at an interval of 6 days to wounds, area of wounds on day 21 was significantly reduced compared with that of non-treated wounds. Application of hGH alone at the same dose had no significant effect on wound healing. The maximum serum hGH concentration after single administration of the hGH collagen film was lower than that with hGH alone, and hGH persisted in serum over 3 days. These results suggest that hGH collagen film may be a useful topical formulation for the treatment of wounds.

Design and synthesis of biocompatible polymeric materials

Abstract For one of the approaches to antithrombogenic materials, the combination of synthetic polymers with physiologically active substances seems to be promising. One of these ways involves crosslinked urokinase (HM-UK), in which urokinases are linked with side chains of poly(2-hydroxyethyl methacrylate) (PHEMA) by 4,4′-diisocyanatodiphenyl-methane, and encapsulated urokinase (HMe-UK), in which urokinases are encapsulated in the network of crosslinked PHEMA. The HMe-UK with a low degree of crosslinking was found to be highly antithrombogenic. For another way, Val-Pro-Arg-immobilized polyetherurethaneurea (PEUU) was synthesized. The tripeptide, Val-Pro-Arg, is a substrate of thrombin. The tripeptide-immobilized PEUU was found to complex specifically with thrombin and inactivate it, and hence to prolong the thrombin time and the active partial thromboplastin time. For a further approach to antithrombogenic materials, the design of materials which are covered with a living tissue formed by cell proliferat...