Periodontal diseases develop, which is cased by factors possessed by a host or life habits such as smoking of the host, in addition to participation of a plurality of periodontal disease-causing bacteria. It is said that approximately 80% of Japanese adults are suffering. It is reported that periodontal diseases not only deteriorate quality of life (QOL) by masticatory function disorder caused by decrease of the supporting function of teeth or loss of teeth, but also constitute risk factors for systemic diseases, such as cardiocirculatory diseases (endocarditis, coronary heart disease), pneumonia, and preterm delivery or low-weight birth. Consequently, the roles of prevention and treatment of periodontal diseases are very important not only for improvement of the QOL of people in Japan or else, where aging is progressing remarkably, but also for clinical practices.
The direct cause of a periodontal disease is periodontal disease-causing bacteria per se or a protease produced by disease-causing bacteria, which causes gingivitis and may eventually extend the inflammation to paradentium advancing to periodontitis. Most of periodontal disease-causing bacteria are Gram-negative obligatory anaerobic bacteria, and examples of typical disease-causing bacteria include Porphyromonas gingivalis, Treponema denticola, Tannerela forsythensis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans. 
As antibacterial agents against such periodontal disease-causing bacteria, β-lactam containing agents, macrolide containing agents, and quinolone containing agents are currently used. However, they have specific characteristics in their antibacterial activities, respectively, and, therefore, an appropriate antibacterial agent should be selected or used in a combination depending on a kind of a disease-causing bacterium or the stage of progression of a periodontal disease. Meanwhile, a problem of a side effect may break out, in case the dosage or the number of doses should increase. Consequently, practical mainstream treatments for periodontitis are mechanical removal of plaque, dental calculus, endotoxin on root surfaces, etc. and surgical ablation of an inflamed tissue. Thus, administration of an antibacterial agent is conducted only as a supportive treatment, except at an acute insult of periodontitis.
Under such circumstances, it has been reported that protamine, which is a basic protein obtainable from a testis of fishes (milt), exhibits inhibitory activity on Arg-gingipain, which is a protease produced by Porphyromonas gingivalis (see Kontani M, and 5 coauthors, “Inhibitory Effects of Protamines on Proteolytic and Adhesive Activities of Porphyromonas gingivalis”, Infection And Immunity, 1999, vol. 67, issue 9, p. 4917-4920). Further, it has been disclosed that periodontitis by periodontal disease-causing bacteria can be effectively inhibited by combining tranexamic acid and/or ε-amino caproic acid with protamine or derivatives thereof (see Japanese Patent Laid-Open No. 2007-169201). The protamine is generally used as a food preservative and highly safe, and consequently has promise as a pharmaceutical alternative to a conventional antibacterial or antibiotic.
Meanwhile, it has been disclosed that protamine exhibits an inhibitory effect against growth of Streptococcus mutans, which is a caries-causing bacterium (see Japanese Patent Laid-Open No. 228526/99), and an inhibitory effect against attachment of oral bacteria (see Japanese Patent Laid-Open No. 2001-89436). Further, the present inventors have found that hydrolysates of a protamine exhibit antifungal activity against fungi such as those belonging to the genus Candida, which cause oral candidiasis (see Japanese Patent Laid-Open No. 2008-133253).
As described above, although it is known that protamine or derivatives thereof exhibit not only antimicrobial activity but also inflammation inhibitory activity on periodontal diseases, the growth inhibitory activity on periodontal disease-causing bacteria per se has not been known yet. Further, since protamine is water-soluble, protamine has been considered to have difficulty to maintain its growth inhibitory activity on periodontal disease-causing bacteria for a long period of time in the oral cavity.
Meanwhile, protamine is a kind of polycations, and it is known that it forms a complex insoluble in water by binding electrostatically with an anionic high molecular compound.
DNAs obtained from testis of fishes similarly to protamine have a large number of phosphate groups in their molecule, which have function as anionic bond elements. Therefore, DNAs exhibit electrostatic affinity for a cationic substance, which can form an electrostatic reaction product with such cationic substance. A DNA molecule is in nature poor in formability and water-soluble, and, consequently, it is difficult to control the in vivo metabolic diffusion speed. It has been disclosed (see Japanese Patent Laid-Open No. 239398/96), however, that a water-insoluble, self-supporting transparent film can be prepared by binding electrostatically a DNA molecule with a cationic artificial lipid.
In the DNA/lipid complex film disclosed in the above patent publication, the DNA molecules as a biopolymer can maintain an orderly double helix structure, to which various low molecular weight compounds can be intercalated in gaps between DNA bases in the double helix structure, or similar low molecular weight compounds can be bound by groove binding in two grooves of the DNA (major groove, minor groove). The above patent publication further discloses a process for producing a medical material by intercalation and/or groove binding of an active pharmaceutical ingredient has been invented (see Japanese Patent Laid-Open No. 2001-327591).
Paying attention to the fact that chitosan, which has been utilized as a medical and/or dental material, is a cationic substance, the present inventors have invented a complex of a DNA molecule and chitosan holding the double helix structure specific to the DNA. Thus, the complex is water-insoluble, and has bio-compatibility, an antimicrobial property, and good formability (see Japanese Patent Laid-Open No. 2005-289852). Further, a process for forming easily a DNA/chitosan complex to a fibrous, spherical, or disk-like form by suspending the same in a phosphate buffer solution (see Japanese Patent Laid-Open No. 2007-97884), and a process for forming a film by press-molding the same under heating (see Japanese Patent Laid-Open No. 2008-110952) have been invented. Since the DNA/chitosan complex and the formed products thereof have excellent biocompatibility and bio-stability, they have had promise as medical and/or dental materials.
However, such problems have become known including the recognized formation of neutrophil, when a DNA/chitosan complex was implanted subcutaneously in a rat, at an initial stage of the implanting probably due to an acute inflammatory reaction; and inadequate activity as an antibacterial or an antibiotic. Consequently, a complex with a cationic substance exhibiting better biocompatibility and antimicrobial activity than chitosan has been desired. Especially in the dental field, development of a material having antimicrobial activity on periodontal disease-causing bacteria has been desired.