[Effect of concomitant use of dental drug on the properties of recombinant human basic fibroblast growth factor formulation for periodontal disease].

We have discussed the essential property for periodontal disease medication using protein, such as recombinant human basic fibroblast growth factor (rhbFGF). In our previous study, the criteria of thickener for the medication, viscosity, flowability etc., were set. The aim of this study was to evaluate the physical and chemical effect of concomitant use of general dental drug or device on thickener properties for the clinical use of viscous rhbFGF formulation. Viscous formulation was prepared with six cellulose derivatives, two types hydroxy propyl cellulose (HPC), three types hydroxy ethyl cellulose (HEC) and methyl cellulose (MC). Antibiotic ointment, local anesthetic, bone graft substitute, agent for gargle and mouthwashes, were chosen as general dental drug and device. These drugs and device were mixed with the viscous formulations and the change of viscosity and flowability, the remaining ratio of rhbFGF were evaluated. When the various thickener solutions were mixed with the liquid drugs, viscosity and flowability did not changed much. However, in the case of MC solution, viscous property declined greatly when MC solution was mixed with cationic surfactant for gargle. The flowabilities of thickener solutions were declined with insoluble bone graft. The stabilities of rhbFGF in thickener solutions were no problem for 24 hours even in the case of mixing with dental drug or device. Our findings suggested that the viscous rhbFGF formulations prepared in this research were not substantially affected by the concomitant use of dental drug or device, especially the formulation with HPC or HEC was useful.

Development of formulation device for periodontal disease.

In addition to providing standard surgical treatment that removes the plaque and infected tissues, medications that can regenerate periodontal tissue are also required in the treatment of periodontal disease. As a form of regenerative medication, various growth factors are expected to be used while treating periodontal disease. A protein-like growth factor is often developed as a lyophilized product with dissolution liquid, considering its instability in the solution state. We have clarified that the formulation for periodontal disease needs to be viscous. When the lyophilized product was dissolved using a sticky solution, various problems were encountered, difficulty in dissolving and air bubbles, for example, and some efforts were needed to prepare the formulation. In this research, to identify the problem of preparing a viscous formulation, a lyophilized product (placebo) and sticky liquid were prepared by using vial and ampoule as the conventional containers. Based on these problems, a prototype administration device was developed, and its functionality was confirmed. As a result, it was suggested that the device with a useful mixing system that could shorten the preparation time was developed.

Evaluation of additives required for periodontal disease formulation using basic fibroblast growth factor.

To design a suitable periodontal disease formulation using basic fibroblast growth factor (bFGF), legally available thickeners were evaluated focusing on their viscosity, extrusive force from a syringe, flow property and inertness to bFGF. Thirteen candidate thickeners showed appropriate viscosity (about 1×104 mPa·s), and further evaluations were conducted on them. Flow property was evaluated by the tilting test tube method. As a result, most thickener solutions with the optimum viscosity showed appropriate flow time (about 100 s) and the flow time did not depend on thickener concentration, whereas the extrusive force from a syringe depended on thickener concentration despite the thickener type and grade. Thickener solutions of 2-3% showed ideal result (10-20 N) and thickener solutions prepared outside of the concentration range (2-3%) were found to show unsuitable extrusive force. Consequently, to obtain required properties for a dental drug formulation, thickener solutions needed to show adequate viscosity (about 1×104 mPa·s) at 2-3% thickener concentration. In addition, several types of cellulose derivatives showed inertness to the bFGF because of their structure, without strong ionic dissociable groups, and neutral pH. Overall, the present work demonstrates that some water-soluble cellulose derivatives, such as hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC), were suggested to have required properties for a dental drug formulation including bFGF.