Cluster dextrinTM (CDex, Highly-branched cyclic dextrin) produced from starch is a glucose polymer which has a cyclic structure in the molecule. Despite its large molecular weight (462 kDa), CDex is highly water-soluble and easily digested with enzymes such as α-amylase. First, the hydroxyl group of the sugar ring of CDex was reacted with octamethylenediamine (OMD) by the 1, 1'-carbonyldiimidazole (CDI) activation method. The obtained product (CDex-OMD) was then labeled with FITC via the amino residue of CDex-OMD. A systemic kinetic analysis of FITC-labeled CDex-OMD (CDex-OMD-F) in rats was carried out by using both a spectrofluorometer and specific high-performance size-exclusion chromatography (HPSEC). Intravenously administered CDex-OMD-F was rapidly eliminated from the blood circulation followed by an appreciable excretion into the urine. HPSEC analysis showed that CDex-OMD-F was quickly degraded into small molecules (∼6 kDa) in the blood. On the other hand FITC-labeled CDex (FCDex) was successfully synthesized by the modified method of de Belder and Granath. Sugar hydroxyl groups of the FCDex were partially activated by periodate oxidation in order to acquire the aldehyde groups to which guest molecules can be bound. The rate of enzymatic degradation of FCDex was controlled by the degree of oxidation. It was found that high NaIO4-treatment extended the blood persistence of FCDex injected intravenously. The prolongation of the circulation time resulted in a high liver uptake followed by a marked fecal excretion. It was suggested that CDex is a liver-specific drug carrier whose biodegradability is controllable by attaching a guest molecule by the NaIO4-oxidation method.
The purpose of this study is to develop new ointments containing the complex of indomethacin (IDM) and lidocaine (LDC) for alleviation of the pain of post-herpetic neuralgia. Methylcellulose-based hydrogel ointment was prepared with a molar ratio of LDC to IDM of 1 or 10.5. The concentration of IDM was fixed at 1% (w/w). The skin permeation of IDM and/or LDC was evaluated using hairless mouse skin with the flow-through-cell method. The amount of IDM permeating from the IDM/LDC (1:1) ointment was about 6-fold higher than that from the ointment containing IDM alone. This can be attributed to the fact that the solubilities of IDM in octanol and water increase in the IDM/LDC (1:1) ointment compared to the ointment containing IDM alone due to the formation of a complex. The amount of IDM permeating from the IDM/LDC (1:10.5) ointment was about 2.2-fold higher than that from the IDM/LDC (1:1) ointment. In contrast, the amount of LDC permeating from IDM/LDC (1:1) ointment decreased to 40% compared to the ointment containing LDC alone (0.65% (w/w)) which was equivalent to the amount used in IDM/LDC (1:1) ointment. However, as the molar ratio of LDC in IDM/LDC ointment was increased from 1 to 10.5 (LDC: 6.9% (w/w)), the amount of LDC permeating from IDM/LDC (1:10.5) ointment was nearly equal to that from the ointment containg LDC alone (6.9%) which is equivalent to the amount used in clinical practice. In such a novel IDM/LDC ointment is a potential formulation to alleviate the pain of post-herpetic neuralgia.
Primary care of periodontitis is to remove the bacterial biofilm around teeth. Periodontal surgery is performed unless the disease was not cured by primary treatment. Flap operation is conventional periodontal surgery performed most often in Japan (400,000 cases/year). This surgery, covered by insurance, removes the infected tissues by separating gingival tissues from root surfaces. However, if periodontal tissue cannot regenerate, novel treatment is required.
The recombinant human basic fibroblast growth factor (rhbFGF), was reported to stimulate proliferation of human periodontal ligament-derived cells subcultured from periodontal tissues.
In this study, the demands on the formulation rhbFGF applied to periodontitis are listed does not leak and diffuses easily at the application site, can be administered to maxillary side, and has appropriate extrusion resistance when administered with syringe even if the amount is less than 1mL. To achieve the demands above, a viscosity is needed as a concept of drug formulation.
In addition, a viscous formulation is expected to improve the rhbFGF remaining at the application site. In order to clarify the selection criteria for viscous additives, viscosity, extrusion, flow characteristics and in vitro drug releasing test were examined using hydroxypropylcellulose as a model additive. Desired formulation characteristics and increased remaining amount of drug at the application site were confirmed.
Furthermore, the issue of viscous formulation as a final administration form reveals that it is necessary to improve the reconstituted characteristic when rhbFGF lyophilized cake is reconstituted using viscous solution.