Thrombosis is characterized by congenital and acquired procatarxis. Nattokinase inhibits thrombus formation in vitro. However, in vivo evaluation of the therapeutic efficacy of nattokinase against thrombosis remains to be conducted. Subcutaneous nattokinase injections of 1 or 2 mg/ml were administered to the tails of rats. Subsequently, ĸ-carrageenan was intravenously administered to the tails at 12 h after nattokinase injections. The mean length of the infarcted regions in the tails of rats was significantly shorter in rats administered 2 mg/ml of nattokinase than those in control rats. Nattokinase exhibited significant prophylactic antithrombotic effects. Previously, the in vitro efficacy of nattokinase against thrombosis had been reported; now our study has revealed the in vivo efficacy of nattokinase against thrombosis.

We have successfully achieved transcutaneous immunization without the use of any skin pre-treatment or immune-stimulant adjuvant by applying a solid-in-oil (S/O) nanodispersion: an oil-based nanodispersion of antigens coated with hydrophobic surfactant molecules. This finding indicates that the S/O nanodispersion has great promise for effective transcutaneous vaccination.

No abstract

No abstract

It is common practice to solubilize a poorly water-soluble drug in an aqueous medium in order to deliver it into the systemic circulation. There are several ways to improve the solubility of drugs including the use of surfactants 1,2) and cogrinding with water-soluble polymers. 3,4) The establishment of pharmaceutical technologies to micronize drug particles at the nano order level is useful to improve drug solubility. 5,6) Besides, micronizing drug particles into the nano-order range is expected to improve drug dissolution rate by increasing the specific surface area of the particles and deliver drugs to the circulation through payer's patches in the gastrointestinal tract. 7)In this study, a practically insoluble drug, griseofulvin (GF), was used as a model. GF is an antibiotic and antifungal drug used in an oral dosage form. It is reported to have a very low solubility (15 mg/ml at 37°C) 8) in water and hence low bioavailability and exhibit variable and incomplete absorption through the gastrointestinal tract (GIT). 8,9) Kraml et al. reported that a 0.5 g dose of micronized GF produced serum levels indistinguishable from those produced by a 1.0 g dose of non-micronized GF, and it was feasible to improve the low serum levels due to low absorption by administering micronized GF. 10) Additionally, the bioavailability of GF was reportedly improved as the specific surface area of the particles increased.11) Therefore, absorption through GIT and bioavailability are expected to be enhanced by reducing the size of GF particles.In general, it is difficult to micronize drug particles into the nanometer range under dry conditions. However, it is feasible to do so in water dispersions using a mechanical process. [12][13][14] In such conditions GF was micronized to a mean particle size of 200 nm. 15) In a study of absorption, different sized particles of Polystyrene microspheres (50-3000 nm) were administered to rats daily for ten days to investigate uptake across the gastrointestinal mucosa.16) The fraction absorbed was 5% for particles of less than 1000 nm, 15% for particles of less than 500 nm and 26% for particles of less than 100 nm, demonstrating the fraction absorbed depended on particle size. We have prepared fine particles of less than 100 nm using a negatively charged phospholipid (dicetyl phosphate: DCP) and high-pressure homogenizer.17) However, DCP had high toxicity, and the suspension had low physicochemical stability at room temperature because of agglomeration in two weeks. Furthermore, it was difficult to maintain the mean particle size below 100 nm after freeze-drying/rehydration. Hence it is necessary to overcome these drawbacks for practical application.In this study, we have used low-toxic and highly biodegradable negatively charged phospholipid (dimyristoyl phosphatidylglycerol: DMPG) to make micronized GF particles less than 100 nm in size, and attempted to maintain the micronized condition for at least half a year. Additionally, we have investigated the behavior of fine particles in suspension, and...