JP2005289852A - Medical material and/or dental material, and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new medical and/or dental functional material using a reaction product (DNA chitosan composite) obtained by a reaction between chitosan and a DNA molecule as a genes and has biocompatibility, antimicrobial properties and good shaping properties, and to provide a method for producing the functional material. <P>SOLUTION: This material comprises the excipient-containing or excipient-free DNA/chitosan composite that is obtained by the electrostatic reaction between DNA and chitosan in which the DNA constituting the composite includes the specific double stranded DNA spiral structure without damage and the composite substantially does not have the solubility in water. Further, the material is used as a medical material and/or a dental material, and the method for producing the same is also provided. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention is for medical and / or dental use using a reaction product (DNA / chitosan complex) having biocompatibility, antibacterial properties and good formability formed from chitosan and a DNA molecule as a gene body. The present invention relates to a new functional material and a manufacturing method thereof.

A DNA molecule that is the main body of a gene is an anionic biopolymer having a large number of phosphate groups that serve as anionic binding elements in the molecule. When attention is paid to the fact that DNA molecules are anionic biopolymers, they exhibit electrostatic affinity for cationic substances and form electrostatic reactants with these cationic substances. It is possible.

Also, DNA molecules that are anionic biopolymers have a double helix structure, and these low helix compounds are intercalated so that various low molecular compounds are sandwiched between the gaps of DNA bases of such a double helix structure. There is a possibility of stably encapsulating low molecular weight compounds. Furthermore, two grooves (main groove and sub groove) possessed by DNA have the possibility of groove-binding similar low molecular compounds. However, since DNA molecules have poor formability and are water-soluble, there are difficulties in adjusting the metabolic diffusion rate in vivo.

Inventor Okabata who paid attention to such technical knowledge has invented “water-insoluble, self-supporting transparent DNA / lipid complex film and production method thereof” as a result of intensive studies (Japanese Patent Laid-Open No. 8-239398). The patent publication discloses “a DNA / lipid complex obtained by electrostatically interacting a phosphate anion portion of DNA with a cationic lipid, wherein the cationic lipid has an association force between lipids. A water-insoluble, self-supporting transparent DNA / lipid complex film comprising the DNA / lipid complex, which is a weak and flexible lipid and in which the double helix structure of the DNA forming the complex is retained without being broken. And the manufacturing method thereof are disclosed.

Specifically, the water-insoluble, self-supporting transparent DNA / lipid complex film disclosed in this publication is made of a biopolymer having an anionic property on a lipid having a long-chain alkyl chain and an ammonium hydrophilic component. It is a water-insoluble DNA / lipid composite film obtained by electrostatic interaction of certain DNA, and the double helix structure of DNA is also retained in this film.

Further, this publication describes that the DNA / lipid composite film can be used as an adsorbent such as a dye, a polarizing film, a conductive film, a molecular separation membrane, a liquid crystal film, and the like. For example, using the double helix structure of DNA, intercalating dyes between DNA base pairs to use as adsorbents, conductivity by intercalating donors or acceptors for electron transfer It is specifically shown to be used as a polymer material by mixing with a film, a molecular separation membrane, a liquid crystal film, or a polymer.

Furthermore, the reaction product of the DNA molecule and artificial lipid itself, or the insolubilized film that has been insolubilized, can be stably retained by intercalating other substances between the double helical bases of DNA. It is shown that it is possible.

Next, the inventors Okabata, Fukushima et al. Pay attention to the characteristics of such DNA molecules, and if this characteristic is used, medicinal components such as antibiotics can be stably supplied to the living body over a long period of time. I thought it would be possible to continue.

In recent years, the concept of a drug delivery system (DDS) has been proposed for the purpose of ensuring effective pharmacological action, reducing side effects of drugs, and effective administration. Because of this drug delivery system (DDS), the application of the DNA-binding agent can be one of the most effective drug application means. For example, infectious diseases have a complex aspect due to the emergence of antimicrobial-resistant bacteria. In particular, in chronic persistent infections where pathogens continue to survive only locally, the situation between the pathogenic microorganism and the host may have a complex effect, and even when antibacterial drugs reach an effective dose, they may encounter a phenomenon that is not eradicated. Not a few. As an example, most of the causative bacteria of the above-mentioned phenomenon in chronic respiratory tract infections are Pseudomonas aeruginosa, and such causative bacteria secrete a mucus substance to form a film-like film (biofilm). The cells in such a biofilm can survive because the frequency of contact with antibacterial agents with high antibacterial activity is drastically reduced, resulting in chronicity and intractability. Although such a phenomenon is explained by the concept of local biofilm infection, it is clear that the conventional administration method of the conventional antibacterial agent can no longer exert its effect sufficiently.

Inventors Okabata, Fukushima et al. Have made an invention of “medical or dental material and method as a result” as a result of researches focusing on these points (Japanese Patent Laid-Open No. 2001-327591). The gazette includes, as a content of the invention, “a biological reaction to foreign matters even when used for a long period of time, including a film using DNA / cationic lipid reactant, which exhibits good formability, biocompatibility and antibacterial properties”. A medical or dental material that can be stably supplied over a long period of time by intercalating and / or groove-binding medicinal ingredients that do not occur and capable of repairing teeth, etc. and a method for producing the same are disclosed. Has been.

The present invention was developed from such a series of research activities “research of reaction product of DNA and cationic substance” by the inventors, Okabata, Fukushima et al. It begins with the selection of chitosan from a number of such cationic substances for the development of medical or dental materials. Then, the characteristics of the reaction product of chitosan and DNA were investigated, and research was conducted on the feasibility and usefulness such as biocompatibility.

Furthermore, as a result of investigation of the background art of the present invention, research and development of complexation of nucleic acid and cationic substance has been promoted in various fields in recent years, and a reaction product of nucleic acid (DNA) and chitosan (nucleic acid / chitosan complex). It has been found that there is a prior invention relating to.

One example is “water-insoluble nucleic acid / chitosan complex and method for producing the same” (Japanese Patent Laid-Open No. 10-77235). Japanese Patent Laid-Open No. 10-77235 discloses a nucleic acid / chitosan complex having a high nucleic acid content, high binding property and excellent stability, and a method for producing the same. A precipitate obtained by mixing a water-insoluble nucleic acid / chitosan complex, a chitosan aqueous solution adjusted to around pH 5 and a nucleic acid aqueous solution, which is precipitated from an aqueous chitosan aqueous solution adjusted to around pH 5 with the binding of Law. " In addition, the publication discloses that “the nucleic acid / chitosan complex of the present invention is applied to aid in molecular biology research such as nucleic acid extraction, separation, purification and protein purification, and can be expected to have a wide range of applications such as drug delivery. "It seems that," the mere expectation is disclosed about the use of the nucleic acid / chitosan complex. However, the above-mentioned publication discloses nothing about the influence on the human body as a medical or dental material of a complex composed of a reaction product of a nucleic acid and chitosan, biocompatibility, operational effects as a medical material, and feasibility. Absent. Therefore, from this known document, the use of the DNA / chitosan complex as a medical or dental material or its technical problem cannot be recalled.

As another example, there is an invention called “nucleic acid-containing complex” (Japanese Patent Laid-Open No. 2001-199903). In this publication, “desired nucleic acid or DNA is sustained for a long period of time at a site requiring treatment, and is taken up by phagocytic cells such as macrophages and delivered specifically to the target site. The invention of “a nucleic acid-containing complex comprising a suitable nucleic acid and a positively charged water-insoluble biodegradable polymer such as chitosan” is disclosed. In this invention, it is said that the nucleic acid-containing complex is particularly suitable in the field of gene therapy, but the constitution is a nucleic acid-containing complex comprising a nucleic acid and a water-insoluble biodegradable polymer that is positively charged. The constituent element is not limited to chitosan as long as it is a positively charged water-insoluble biodegradable polymer. That is, the technical main part of the present invention is to supply a desired nucleic acid to a site requiring treatment by utilizing the natural law of excellent nucleic acid-releasing property of the nucleic acid-containing complex, and to provide a nucleic acid specific to the target site. It enables functional expression of. This is only a material that can synthesize a nucleic acid-containing complex and can realize excellent nucleic acid sustained release.

On the other hand, the present invention does not require nucleic acid sustained release, nor is it intended for nucleic acid supply or nucleic acid functional expression. The DNA used in the present invention only needs to be a reaction product of DNA having a double helix structure and chitosan, and can be widely used as a medical or dental material. The idea is different.

As yet another example, there is a prior invention “a composition suitable for gene delivery to epithelial cells” (Japanese Patent Publication No. 2001-500109). In this publication, “a nucleic acid encoding a vaccine, a drug, an enzyme, or an antisense agent is delivered to the epithelial surface of a mammal and has a surface charge. The invention of “granular composites” is disclosed.

However, the invention of this publication discloses that the nucleic acid is a vascular endothelial growth factor gene, a hepatocyte growth factor gene, or a nucleic acid encoding a drug or an enzyme, such as a nucleic acid that expresses functional expression information such as a gene or encoding nucleic acid. It is an invention relating to a therapeutic technique by conjugation, and it is essential that the nucleic acid used contains functional information and can be expressed.

On the other hand, the DNA used in the present invention can be widely used as long as it has a double helix structure, has specific function expression information essential for gene therapy, etc., and there is no need to express it. The reaction product of DNA and chitosan of the present invention can be widely used as a medical or dental material, and both have different basic technical ideas.
JP-A-8-239398 “Water-insoluble, self-supporting transparent DNA / lipid complex film and production method thereof” Japanese Patent Laid-Open No. 2001-327591 “Medical or Dental Material and Method for Producing the Same” JP-A-10-77235 “Water-insoluble nucleic acid / chitosan complex and method for producing the same” JP 2001-199903 A “Nucleic acid-containing complex” JP 2001-500109 A “Composition suitable for gene delivery to epithelial cells”

As described above, the present invention is based on the disclosed technology disclosed in Japanese Patent Laid-Open No. 2001-327591 “A possible medical or dental material using a DNA / cationic lipid reactant”, which is a result of prior research by the inventors. It was developed by further promoting the basic idea. Although there exists a complex of nucleic acid and chitosan as a conventional technique, the complex exists for a completely different purpose and use, and the essential technical idea is different from the present invention. This is another invention.

In particular, a DNA complex that can be used as a medical or dental material is not only relative to the physical properties of the DNA complex itself and the characteristics of the constituent substance itself, but also relative to the human body and physiological phenomena to be used. This is because relevance is a more important prerequisite. In other words, medical or dental materials are intended for the human body at all times, and it is absolutely necessary to ensure safety for living bodies such as biocompatibility, cytotoxicity and antibacterial properties. It is. Even if the constituents of the DNA complex are used, if different physical properties are used and different natural laws are used, the technical idea is different, which is a completely different invention.

In contrast to the above-described prior invention, the present inventors have selected chitosan from among cationic substances that can react with a large number of DNAs to form a complex. Moreover, the chitosan not only has the property of reacting with DNA to form a complex, but also has a relative compatibility with the human body and physiological phenomena to be used even when used for medical or dental purposes. I got new technical knowledge that is very good.

In addition, the present invention is intended to provide a new functional material for medical or dental use using a reaction product of DNA and chitosan (hereinafter referred to as DNA / chitosan complex). More specifically, the present invention comprises a shaped article and a non-shaped article having a good shape, biocompatibility and antibacterial properties and having a shape suitable for medical use and dental use. It was developed as a safe medical or dental material that does not cause a biological reaction to foreign substances even when used.

Further, the present invention can intercalate and / or groove bind medicinal ingredients by utilizing the characteristics of DNA, and the intercalated and / or groove bound medicinal ingredients can be used for a long period of time. It is intended to provide a medical or dental material that can be supplied stably over a wide range.

Furthermore, even when such a medicinal component is not intercalated or groove-bound, a regenerative medical material or a regenerative dental material capable of repairing, for example, a tooth using the characteristics inherent to DNA. Is intended to provide.

As described above, the DNA / chitosan complex is highly safe and excellent in relative compatibility with humans to be used, such as biocompatibility and antibacterial properties. It has the usefulness of including, delivering, and releasing a wide range of low molecular weight compounds, and also has ease of handling that makes it easy to adjust the formability and form / shape. Thus, it was found that the DNA / chitosan complex exhibits excellent compatibility and properties for medical or dental use. Therefore, the present invention aims to provide a new functional material mainly composed of a DNA / chitosan complex as a medical material or a dental material and to provide a preparation method thereof.

The first invention to be patented is a shaped product of a DNA / chitosan complex obtained as an electrostatic reaction product of DNA and chitosan, and the DNA forming the complex is divided into two DNA-specific DNAs. A medical material and / or a dental material in which a material having a double helical structure is left and the composite is substantially insoluble in water. is there.

In the first invention, a shaped product produced by shaping a DNA / chitosan complex, which is a reaction product of DNA and chitosan that reacts electrostatically with the DNA, is used as a medical or dental material. It is a thing. Moreover, it is necessary that the DNA / chitosan complex is left without breaking the double helix structure peculiar to DNA and that the DNA / chitosan complex is insoluble in water. . This is because, when the double helix structure is broken, the function of intercalating and / or groove binding a low molecular weight compound, which is an important characteristic, is lost and usefulness is lost. Further, when the DNA / chitosan complex has water solubility, the DNA / chitosan complex itself cannot be precipitated and separated. In this way, it is meaningful to exclude cases where substantial practicality is lacking.

The DNA molecule that is a constituent element of the present invention is an anionic biopolymer having a large number of phosphate groups that serve as anionic binding elements in the molecule. When attention is paid to the fact that DNA molecules are anionic biopolymers, they exhibit electrostatic affinity for cationic substances and form electrostatic reactants with these cationic substances. It is possible.

In contrast, chitosan as a constituent element selected in the present invention is a deacetylated polyglucosamine obtained by alkali treatment of chitin obtained from crab shells or shrimp shells, and is a cationic substance. Therefore, when a DNA aqueous solution and a chitosan aqueous solution are mixed, the DNA and chitosan react electrostatically, and a water-insoluble DNA / chitosan complex precipitates in the solution as a precipitate. If this is separated, a DNA / chitosan complex can be easily obtained.

When DNA is irradiated with ultraviolet rays, the ultraviolet rays are absorbed by the DNA base, and a cross-linked structure is formed between the DNA molecules so as to be insoluble in water. By utilizing this characteristic, a DNA / chitosan complex can be produced even from chitosan which cannot form a shaped product by a usual method.

When the characteristics of the DNA / chitosan complex, which is an electrostatic reaction product of DNA and chitosan thus obtained, were examined, it was a suitable substance for use in medical or dental applications as follows. I understand.

The DNA / chitosan complex is excellent in biocompatibility and antibacterial properties, and does not cause a biological reaction or an allergic reaction to a foreign substance even when used for a long time by transplantation. The reactant used in the medical or dental material of the present invention exhibits a very good biocompatibility, so that it does not cause a biological reaction to foreign substances such as immune reaction, allergy, inflammatory reaction, and thrombus reaction. Also, it has no carcinogenicity or teratogenicity. Therefore, the above-mentioned shaped article used as the medical or dental material of the present invention has very good biocompatibility as described above as well as flexibility. That is, it is considered that the shaped product used as the medical or dental material of the present invention is extremely difficult for the living body to recognize as a foreign substance. Furthermore, since the medical or dental material of the present invention used in the living body is decomposed into deoxyribonucleic acid and glucosamine that are harmless to the living body, it has high safety. Therefore, the reactant according to the present invention is suitable as a medical or dental material and can be used in a very wide range.
The DNA / chitosan complex has a good shapeability and can be a shaped product having a shape suitable for medical use and dental use. In the dental material of the present invention, a part of the phosphate group, which is an anionic group of DNA, and the cationic group of chitosan are electrostatically bonded to express a desired formability. It is.
The DNA / chitosan complex has a double helix structure that DNA has, and can stably hold other substances between the bases of the double helix structure or in the groove. By utilizing the characteristics of this DNA, it is possible to intercalate and / or groove bind low molecular compounds such as medicinal ingredients and osteogenesis-inducing factors. By utilizing this intercalating and / or groove binding action, it is possible to easily enclose, deliver, and supply a medicinal component or the like. In particular, the fact that a medicinal component held by intercalation and / or groove binding can be transplanted to an affected area in a living body, and the medicinal component can be delivered to the affected area in a stable manner over a long period of time. Or it becomes a suitable function very useful for the dental treatment act.
By utilizing the phosphate group inherent in the DNA of the DNA / chitosan complex, for example, teeth and bones can be regenerated and repaired, and can be used as a scaffold for regenerative medicine or a scaffold for regenerative dentistry. . In the DNA / chitosan complex of the present invention, a part of a phosphate group which is an anionic group of DNA and a cationic group of chitosan are electrostatically bonded to express a desired shaping property. However, a large number of phosphate groups that are not bound to chitosan remain in the DNA. This phosphate group in DNA can be used by electrostatically binding to bone regeneration-inducing factor (BMP) or fibroblast growth factor (FGF). For example, tooth regeneration (specifically, reconstruction of a hydroxyapatite structure, etc.) can also be performed by directly using it.
The DNA / chitosan complex has substantially no solubility in water. Since DNA inherently dissolves in water, it cannot be shaped by using this DNA alone. In the present invention, an anionic DNA and the cationic chitosan are electrostatically reacted utilizing the fact that the DNA has an anionic property, and substantially dissolved in water. No longer. The DNA / chitosan complex is insoluble in organic solvents and cannot be cast by the casting method. However, the borate buffer-treated DNA / chitosan complex suspension according to the present invention has fluidity. Molding is possible by using this property.

The second invention to be patented is a non-shaped form of a DNA / chitosan complex obtained by an electrostatic reaction product of DNA and chitosan, and the DNA forming the complex is unique to DNA. A medical material and / or dental material in which the double helical structure is retained, and the composite is substantially insoluble in water. Material.

The second invention is different from the first invention only in the form of an unshaped object. Even in the non-shaped form, the DNA / chitosan complex has the important characteristics of the first invention, and is excellent in biocompatibility and antibacterial properties. And / or a groove binding function, which is fully useful depending on how it is used.

The third invention to be patented includes the medical material according to claim 1 or 2, wherein the DNA forming the DNA / chitosan complex is natural DNA and / or synthetic DNA. Or a dental material.

The third invention clarifies the scope of the concept of the DNA of the present invention. As the DNA forming the medical or dental material of the present invention, either natural DNA or synthetic DNA can be used. Examples of the natural DNA used in the present invention include lambda phage DNA of bacterial virus, Escherichia coli chromosomal DNA, calf thymus DNA, and salmon sperm DNA. Synthetic DNA can be synthesized by a synthesizer using poly (dA), poly (dT), poly (dG), poly (dC), poly (dA-dT), poly (dG-dC), etc. Various synthetic DNAs with different base sequences; synthesized by a synthesizer using poly (A), poly (T), poly (G), poly (U), poly (AT), poly (GU), etc. Possible various synthetic RNAs with different base sequences;
Complementary, which can be synthesized by a synthesizer using DNA / RNA hybrids such as poly (dG), poly (U), poly (G), poly (dC) poly (dA-dT), poly (AT) Mention may be made of DNA / RNA hybrids having base pairs. These can be used alone or in combination as required.

Such DNA has various groups (for example, phosphate-containing groups) on four types of bases [cytosine (C), guanine (G), adenine (A), thymine (T)] forming a double helix. The whole DNA has an anionic property due to, for example, a phosphate group bonded to the above-mentioned terminal.

Such a DNA itself is a string having a double helix structure, and since this DNA is dissolved in water, it cannot be shaped by using this DNA alone. In the present invention, an anionic DNA and the cationic chitosan are electrostatically reacted utilizing the fact that the DNA has an anionic property, and substantially dissolved in water. No longer.

The fourth invention to be patented is characterized in that the chitosan forming the DNA / chitosan complex has a molecular weight of 320 (number of glucosamine residues 2) or more. Medical materials and / or dental materials.

The fourth invention specifies and explains the concept of chitosan that reacts electrostatically with the DNA. The chitosan can be prepared using crab and shrimp shells, insects, plants, microorganisms and the like as raw materials. In the present invention, chitosan used for forming the complex may be chitosan having a molecular weight of 320 (number of glucosamine residues 2) or more, preferably a molecular weight of 1600 (number of glucosamine residues 10) or more. This is preferably chitosan having a molecular weight of 10,000 or more in order to express insolubility of DNA in water. Further, when chitosan having a small molecular weight and forming a salt with hydrochloric acid or the like is used, the reaction product with DNA is water-soluble, and it is difficult to separate this reaction product from an aqueous medium that is a solvent for DNA. Therefore, it is not suitable for the purpose of forming a complex.

The fifth invention to be patented is characterized in that the DNA / chitosan complex is intercalated and / or groove-bounded with a low molecular weight compound having a molecular weight of approximately 300 to 1300 Da. Medical materials and / or dental materials.

The fifth invention is a basic invention that utilizes the function of intercalating and / or groove binding a low molecular weight compound, which is a major characteristic of DNA / chitosan complexes. In the reaction product forming the medical or dental material according to the present invention, the double helix structure of the DNA is maintained because the obtained complex is subjected to a known analysis method such as an X-ray diffraction method. It could be confirmed from the obtained results. Such characteristics of the DNA structure can be used for medical or dental materials as follows. The low molecular weight compound can be stably encapsulated by intercalating so that various low molecular weight compounds are sandwiched in the gap between the DNA bases in the reaction product of DNA and chitosan according to the present invention. In addition, the same low molecular weight compound can be groove-bound in two grooves (main groove and sub groove) having a double helical structure of DNA. The molecular weight of low molecular weight compounds that intercalate or group bind well with DNA is distributed in the range of approximately 300 to 1300 Da. Therefore, many desired drugs including antibiotics are included in DNA. There is a possibility. Moreover, since the content of the interaction between the two is completely different in each case, it can be said that there is a high possibility that intercalation or groove binding can be used depending on the specific application method. Therefore, if the characteristic of such DNA is utilized, the reaction product of DNA containing this and chitosan can be used as a drug delivery system. Drugs included are extremely diverse, including anti-infective drugs such as antibiotics and antibacterial agents, anticancer drugs, anti-inflammatory drugs, analgesics, hemostatics, and other drugs. It is closely related to usage.

The sixth invention to be patented is to intercalate and / or groove bind a medicinal component, a bone regeneration-inducing factor, a fibroblast growth factor, or a tissue regeneration-inducing factor to the DNA / chitosan complex. Alternatively, it is a medical material and / or a dental material characterized by delivering and supplying a bone regeneration inducing factor, a fibroblast growth factor, or a tissue regeneration inducing factor.

The sixth aspect of the present invention is an invention showing a utilization aspect when a DNA / chitosan complex relating to a medical material and / or a dental material is used as a delivery system for a medicinal component or the like.
Specific examples of drugs that can be used for the above purpose include amphotericin B, nystatin, flucytosine, miconazole, fluconazole, itraconazole, griseofulvin, terbinafine, and the like as antifungal drugs for internal use, and pimaricin, tricomycin and the like. It is done. Further, as an anticancer agent, nitrogen mustard hydrochloride-N-oxide, chlorambucil, melphalan, cyclophosphamide, ifosfamide, busulfan, improsulfan tosylate, carbocon, thiotepa, tacarpazine, simustine hydrochloride, ranimustine, carmustine, Examples include alkylating agents such as lomustine, semustine, and streptozocin. Furthermore, antimetabolites such as methotrexate, 5-fluorouracil, carmofur, tegafur, doxyfluridine, floxuridine, cytarabine, ancitabine hydrochloride, enositabine, mercaptopurine, thioinosine-6-mercaptopurine riboside, 6-thioguanine, 5-azacytidine It is done. Examples of anticancer antibiotics include doxorubicin hydrochloride, daunorubicin hydrochloride, aclarubicin hydrochloride, epirubicin hydrochloride, pirarubicin, pepromycin sulfate, preomycin hydrochloride, bleomycin sulfate, mitomycin C, actinomycin D, chromomycin A3, neocartinostatin and the like It is done. In addition to plant-derived etoposide and teniposide, plant alkaloids such as vinblastine sulfate, vincristine sulfate and vindesine sulfate are also included. Furthermore, examples of immunotherapeutic agents include OK-432, PSK, lentinan, schizophyllan, ubenimex, interferon-α, interferon-α-2a, interferon-α-2b, interferon-β, and interferon-γ. Besides, tamoxifen citrate, diethylstilpesterol phosphate, megestrol acetate, estramustine phosphate phosphate, mepithiostan, epithiostanol and other hormones, cisplatin, carboplatin and other platinum complexes, L-asparaginase, procarbazine hydrochloride, Examples thereof include mitoblonitol, mitoxantrone hydrochloride, acegraton, mitotane and the like.

The above-described drug intercalation and groove binding to DNA are usually performed in an aqueous solution. For example, intercalation and groove binding can be easily performed by an addition method in which a drug solution is dropped into a solution containing DNA while stirring. The binding force between drug and DNA and the mode of interaction are affected by the affinity of DNA with bases, sugar residues, etc., the state of spatial arrangement, and the like. Therefore, in addition to the drug selection, preferably the conditions such as concentration, pH, ionic strength, temperature, etc., and the type of reaction medium such as phosphate or tris buffer or isotonic saline are appropriately selected. Alternatively, by adjusting, an optimal method of intercalation or groove binding is found. Furthermore, the specific delivery method and mode of the encapsulated drug, release conditions, and the like can be appropriately determined by adjusting the conditions governing the above-described interaction. On the other hand, it can also be applied as a selective adsorbent in vivo by utilizing the fact that DNA interacts specially with various substances and can be selectively accumulated and separated in the complex by the above-mentioned intercalation.

The seventh invention to be patented is a solution formulation, a dispersion formulation, a semi-solid formulation, a granule obtained by intercalating and / or groove binding a medicinal component to the non-shaped form of the DNA / chitosan complex. A medical material and / or a dental material, characterized in that it is formed into a dosage form of either a body preparation or a molded preparation.

The seventh invention is an invention in which a non-shaped form of a DNA / chitosan complex is included in a medicinal component and formed into a dosage form. Since the DNA / chitosan complex according to the present invention is in the form of a non-shaped object, the mode of use as a medical or dental material is diverse and is not limited to a specific object or application. Therefore, what is shown below is an example of a specific mode of use and presents the best mode.

Regarding the DNA / chitosan complex according to the present invention, an embodiment in which an unshaped form is used as a medical or dental material is not particularly limited. Available at. For example, it can be broadly classified to include various dosage forms such as solution preparations, dispersion preparations, semi-solid preparations, granular preparations and molded preparations. Furthermore, the composition of the dosage form and the application method thereof are the same as those of ordinary drugs. For example, specific examples of solution preparations include injections and oral drugs, and specific examples of dispersion preparations include spray sprays used for the treatment of athlete's foot and the like. Furthermore, in the case of oily semi-solid preparations and granular preparations, it can be used for ointments such as wounds, patches, bandages, artificial skins and the like. Moreover, in the case of a granular preparation, various uses can be performed as an additive. Other use modes include wound dressings, hemostatic materials, various hygiene products, and the like.

In the eighth invention to be patented, an antibacterial agent is intercalated and / or groove-bound to a shaped article comprising a DNA / chitosan complex to deliver and supply the antibacterial agent to an affected area or a necessary place. This is a dental material characterized by the above.

The eighth invention is an invention when the DNA / chitosan complex is also used as an antibacterial material. For example, if desired, the water-insoluble DNA / chitosan complex of the present invention can be shaped and used as a medical or dental material. Although it has already been described that the double helix structure derived from DNA and two grooves remain in this shaped product, the main groove or the sub groove, or between the bases forming this double helix structure In addition, by including a low molecular compound, the shaped product can stably hold the low molecular compound for a long period of time. For example, by embedding a sheet obtained by intercalating or groove-binding a low-molecular compound as a drug in oral tissues, the low-molecular compound included in DNA can be gradually released over a long period of time. These agents can also be used as antibacterial materials for preventing infection or inflammation by intercalating or groove binding to DNA in the DNA / chitosan complex shaped article.

The ninth invention to be patented is to intercalate and / or groove bind an anti-periodontopathic agent to a shaped article composed of a DNA / chitosan complex so that the anti-periodontal agent is applied to an affected area or a necessary place. A dental material characterized in that it is delivered and supplied.

In a ninth aspect of the present invention, in the dental field, a chemical solution that can resist periodontal disease bacteria is intercalated and groove-bound to the DNA / chitosan complex shaped article that is the dental material of the present invention, and this sheet is used as a gum. By embedding in the vicinity of the affected area, it is possible to realize that the anti-periodontal drug solution is released to the affected area over a long period of time. Periodontal disease is caused by various bacteria, and examples of drugs against these bacteria (anti-periodontal drugs) include amoxicillin, ofloxacin, minocycline, amphotericin B, and metronidazole. In addition, no inflammatory reaction or allergic reaction is caused by the insertion of such a film.

The tenth invention to be patented is to intercalate and / or groove bind the osteogenesis inducer to the shaped article comprising the DNA / chitosan complex, and deliver the osteogenesis inducer to the affected area or a necessary location. A dental material characterized by being supplied.

The eleventh invention to be patented is a membrane, film, or lining manufactured using a drug / tissue regeneration-inducing factor intercalated and / or groove-bound to an excipient comprising a DNA / chitosan complex. A dental material, such as a material or a coating material, wherein the drug or tissue regeneration-inducing factor is delivered and supplied to an affected area or a necessary location.

The twelfth invention to be patented is a solution formulation, a dispersion formulation, a semi-solid formulation, a granule obtained by intercalating and / or groove binding a medicinal component to the non-shaped form of the DNA / chitosan complex. Formed into any dosage form of body preparations or molded preparations, which are added to the raw material as an additive to produce medical materials and / or dental materials, and deliver medicinal ingredients through the dental materials A medical material and / or a dental material characterized by being supplied.

According to the twelfth aspect of the present invention, there is provided a medical material produced by adding a medicinal component to a non-shaped form of a DNA / chitosan complex to form a dosage form, and adding this to a raw material, and / or It is an invention of a dental material. By using the DNA / chitosan complex as an additive, it becomes possible to hold and deliver a medicinal component to various medical and dental members by mixing the medicinal component with various raw materials. .

The thirteenth invention to be patented is a solution formulation, a dispersion formulation, a semi-solid formulation, a granular material obtained by intercalating and / or groove binding a medicinal component to a non-shaped form of DNA / chitosan complex It is formed into any dosage form of the preparation or molded preparation, and it is a primer, bonding agent, composite resin, temporary sealing material, back layer material, root canal filling material, periodontal dressing material, which is added as an additive. Manufacture dental materials such as cement for cement, direct bonding materials, dentures, rebase materials, and antibacterial agents for dentures, and deliver and supply the medicinal ingredients to affected areas and necessary places via the dental materials This is a dental material characterized by the above.

The thirteenth invention is a specific embodiment invention in the case of using the DNA / chitosan complex in the dental field of the twelfth invention as an additive. In the case of this utilization mode, it is particularly useful in the dental field.

The fourteenth invention to be patented contains a scaffold for regenerating bone tissue and periodontal tissue using a DNA / chitosan complex shaped article, and is contained in the scaffold when transplanted. Regeneration characterized by forming a hydroxyapatite structure using phosphate residues, depositing a lime compound, or using it as a bone supplement carrier to regenerate bone tissue and periodontal tissue Medical materials and / or regenerative dental materials.

The fourteenth aspect of the present invention is a regenerative medical material that can be used as a scaffold for regenerating bone tissue and periodontal tissue using a DNA / chitosan complex shaped material and can regenerate bone tissue and periodontal tissue. Or it is a basic invention of a regenerative dental material. The DNA / chitosan complex according to the present invention can be used in various forms as a medical or dental material such as a wound dressing, a hemostatic material, various hygiene products, in the form of a shaped or non-shaped article, The use as a scaffold material for regenerative medicine is particularly suitable. In the field of dentistry, DNA / as a new dental material capable of covering a membrane, a recalcification promoting material, a pulp or a periodontal tissue contacting portion placed under a gingival flap in the periodontal tissue regeneration induction method. Chitosan complex shaped articles can be used.

The method of regeneration when using a DNA / chitosan complex excipient varies depending on the site to be transplanted and the environmental conditions, but it has excellent biocompatibility, so it is easy to use because the rejection reaction is suppressed. is there. Since the phosphate group of DNA is a component of bone, it is expected to be used in the dental field. The seventeenth invention is an embodiment as a regenerative dental material in the dental field.

The fifteenth aspect of the invention to be patented is a scaffold formed by using a shaped article comprising a DNA / chitosan complex, the scaffold using a phosphate residue contained by transplanting This is a regenerative dental material characterized in that a hydroxyapatite structure is formed on the surface.

In the regenerated dental material of the fifteenth aspect of the invention, a part of the phosphate group, which is an anionic group of DNA, and the cationic group of chitosan are electrostatically bonded to express a desired shaping property. Therefore, a large number of phosphate groups that are not bound to chitosan remain in the DNA. This phosphate group in DNA can be used by electrostatically binding to bone regeneration-inducing factor (BMP) or fibroblast growth factor (FGF). For example, tooth regeneration (specifically, reconstruction of a hydroxyapatite structure, etc.) can be performed by directly using it.

Moreover, the DNA / chitosan complex shaped article of the present invention can be used as a recalcification accelerator for depositing calcified material on the tooth surface. That is, a phosphate group remains in the DNA molecule, and the DNA / chitosan complex shaped article in which the phosphate group remains can regenerate the hydroxyapatite structure that forms the tooth due to the presence of calcium. Can do. Therefore, by placing the DNA / chitosan complex shaped article, which is the dental material of the present invention, on the tooth portion that needs to be remineralized, the surrounding calcium is absorbed and a hydroxyapatite structure is newly added to this portion. Can be formed.

The sixteenth invention to be patented is a membrane formed by using a shaped product comprising a DNA / chitosan complex, and the membrane is made of a hydroxyl group utilizing a phosphate residue contained by transplantation. A regenerative dental material characterized in that an apatite structure is formed.

The sixteenth invention is an invention in which a membrane is placed under a gingival flap in a tissue regeneration induction method (GTR method) for regenerating lost periodontal tissue. This membrane is an environment-forming material that shields the epithelial tissue that proliferates deeply at the defect site to regenerate alveolar bone, periodontal ligament, cementum, and the like. Since this membrane is kept in the living body for a certain period of time, it is preferably formed of a material having high biocompatibility. As such a membrane, an absorbable membrane based on collagen or polylactic acid and fluorine are used. A non-absorbent membrane using resin is used. A GTR membrane can be produced from the DNA / chitosan complex shaped material forming the dental material of the present invention. Thus, the GTR membrane manufactured using the dental material of the present invention has high biocompatibility and can be used stably over a long period of time compared to conventional membranes. Moreover, if the GTR membrane manufactured using the dental material of this invention is used, a reproduction | regeneration period can be set longer than the case where the conventional absorptive membrane is used.

Moreover, since the membrane manufactured with the dental material of the present invention has extremely high biocompatibility, there is an advantage that secondary treatment for removal is not necessarily required after treatment. Furthermore, in the above GTR method, as another application mode of the GTR membrane produced from the DNA / chitosan complex shaped article of the present invention, an enamel matrix having a possibility of regenerating periodontal tissue by forming acellular cementum When the derived protein is used in combination, it can also be used as a carrier for applying the protein.

The seventeenth invention to be patented is a tooth surface coating material formed using a shaped article comprising a DNA / chitosan complex, in which a lime compound is deposited on the coated tooth surface to regenerate the tooth. A regenerated dental dressing characterized in that calcification is promoted.

In addition, using the biocompatibility and antibacterial properties, the surface of an artificial dental member that comes into contact with the pulp or periodontal tissue is formed with the DNA / chitosan complex shaped article of the dental material of the present invention. By covering, it is possible to prevent a biological reaction from being caused by the dental member. That is, the dental material of the present invention can be used as a coating material or a lining material for covering the surface of a dental member.

For example, the bone affinity can be further improved by coating the surface of the implant with a film made of the DNA / chitosan complex which is a dental material of the present invention as an implant surface treatment agent, or a bone filling material It can be used as a carrier. In addition, by using the DNA / chitosan complex shaped article which is a dental material of the present invention, a biological reaction to a foreign substance can be prevented by covering a portion in contact with the pulp or periodontal tissue. Specific examples include periodontal dressings and artificial skin.

The eighteenth invention to be patented is formed into a film, a lining material, a coating material, a dressing material or artificial skin by using a shaped article comprising a DNA / chitosan complex, and this is used to produce a medical material and / or Or a medical material and / or a dental material characterized in that the biocompatibility when transplanted is improved by coating a dental material, or a biological reaction to a foreign body is suppressed. is there.

The eighteenth invention is an invention when used in such a manner that the biocompatibility when the DNA / chitosan complex is transplanted is improved or the biological reaction to the foreign substance in the living body is suppressed. For example, the bone affinity can be further improved by coating the surface of the implant with a film made of the DNA / chitosan complex which is a dental material of the present invention as an implant surface treatment agent, or a bone filling material It can be used as a carrier. In addition, by using the DNA / chitosan complex shaped article that is a dental material of the present invention, a biological reaction to a foreign substance can be prevented by covering a portion that comes in contact with the dental pulp or periodontal tissue. Specific examples include periodontal dressings and artificial skin.

The nineteenth invention to be patented is a DNA / chitosan complex in which the form, shape and porosity of a reaction product obtained by reacting DNA with chitosan and washing with a buffer solution are adjusted. A method for preparing a medical material and / or a dental material.

The DNA / chitosan complex according to the present invention is obtained by the reaction of chitosan and DNA, and specifically, it is generally carried out in an aqueous solution. That is, an aqueous solution containing biological DNA or synthetic DNA obtained by a synthesis process is added to a stirring aqueous solution of chitosan and reacted while stirring, and the resulting precipitate is obtained by centrifugation. The precipitate thus obtained is washed with a buffer solution, centrifuged again, washed with water and dried to obtain a DNA / chitosan complex. However, as a result of the experiment, the DNA / chitosan complex obtained in the above preparation method has a characteristic and a shape in the DNA / chitosan complex, particularly porosity, which are important characteristics as a medical or dental material. It has been found that the pore diameter is different when the type of the buffer solution is changed. Therefore, the twentieth invention and the twenty-first invention were made. This means to adjust the form and shape of the reactants and the porosity suitable for the application and request, for example, the tissue invades such pores, easily become a scaffold for cells, This is a technology that plays a major role in practical application.

The twentieth invention to be patented is a tris buffer solution, borate buffer solution, HEPES buffer solution, acetate buffer solution, citrate buffer solution as necessary for washing a buffer solution for washing the reaction product of DNA and chitosan. , Glycine buffer, barbiturate buffer, phthalate buffer, cacodylate buffer, carbonate buffer, Bis-Tris buffer, Bis-Tris-propane buffer, MES buffer, ADA buffer, PIPES buffer , ACES buffer, collamine chloride buffer, BES buffer, MOPS buffer, TES buffer, HEPPS buffer, Tricine buffer, glycinamide buffer, Bicine buffer, TAPS buffer, CHES buffer, CAPS buffer It is characterized in that the form, shape, and porosity of the reaction product obtained by washing with a specific buffer selected from a liquid, phosphate buffer, etc. are prepared. The method for preparing a medical material and / or a dental material according to claim 19.

The inventors have obtained a new technical knowledge that, when a precipitate deposited by the reaction between DNA and chitosan is washed with a buffer, the form and shape in the DNA / chitosan complex, in particular, the porosity and the pore diameter can be changed. I found it. Any of the above-mentioned many buffer solutions can be used to adjust the form, shape and porosity of the reaction product.

The twenty-first invention to be patented is that a DNA / chitosan complex is put into a borate buffer solution to form a fluid suspension, and the fluid suspension is molded into an arbitrary shape. This is a method for preparing a medical material and / or a dental material.

The 21st invention is an invention of a new shape molding method when a DNA / chitosan complex is used as a medical or dental material. The mode of using the DNA / chitosan complex as a medical or dental material is not limited as described above, and can be used in a wide variety of forms and shapes. As one form thereof, there is a method of shaping this reaction product. For shaping, a commonly used method may be used. However, as in the present invention, the DNA / chitosan complex is treated with boric acid. It can be made into a suspension with a fluidity by putting it in a buffer solution, and it can be molded into any shape from the suspension with fluidity, or made of Teflon with a DNA / chitosan complex placed on a filter. If it is poured into a ring, filtered, and freeze-dried, it becomes a disk-like form. Therefore, a molded product of any form can be obtained by adjusting the form of the mold. Further, if the buffer solution is selected as described above, the porosity can be adjusted.

As described above, the DNA / chitosan complex, which is a dental material of the present invention, has extremely good biocompatibility and antibacterial properties, so that it is used for medical or dental purposes for the human body. Suitable as a material.

The DNA / chitosan complex according to the present invention may be used as a shaped product or in the form of a non-shaped product. As materials, scaffolds for regenerative medicine (scaffold materials), biocompatibility improvers for transplant materials, other antibacterial agents, hemostatic materials, various hygiene products, and other medical or dental materials it can.

In addition, the DNA / chitosan complex shaped material, which is the dental material of the present invention, can intercalate or groove bind low molecular weight compounds by the double helix structure that DNA molecules essentially have. Therefore, it has a delivery system (DDS) function capable of holding a tissue regeneration inducer (GTR) or a drug, and delivering and supplying it to a necessary location such as an affected part. Specifically, it can be used as a new membrane, film, lining material or coating material having a tissue regeneration inducer (GTR) or drug delivery function.

  In particular, the present invention is highly useful in the dental field. Specifically, the dental material of the present invention is said to be particularly useful as a film, membrane, lining material or coating material utilizing a tissue regeneration inducer (GTR) or drug delivery system (DDS) function. It has been broken. The specific reason is as follows. In other words, the DNA / chitosan complex shaped material, which is a dental material of the present invention having excellent biocompatibility, contains phosphate groups necessary for bone formation, which are inherently possessed by DNA molecules. By using this, it has a function of a delivery system (DDS) for delivering various substances such as medicinal ingredients when desired. Therefore, it is possible to incorporate various drugs into the shaped product of the DNA / chitosan complex by intercalation or groove binding. Since the incorporated drug is not covalently bonded tightly to the excipient, the incorporated drug can be selectively released at the point of action. Moreover, the discharge amount, period, etc. can be set. For example, by holding anti-infective drugs such as antibiotics and antibacterial drugs, anti-inflammatory drugs, analgesics, hemostatic drugs and other drugs in a shaped article, as a drug administration method different from internal use, gingiva, It can be used for administration directly into the pulp or periodontal pocket. By way of example, agents for the treatment of periodontal disease can include the antibacterial agents amoxicillin, ofloxacin, minocycline, the antifungal agent amphotericin B, and the antiprotozoal agent metronidazole. As another example, cytokines such as bone regeneration-inducing factor (BMP) and fibroblast growth factor (FGF) can be used as a carrier for penetrating tissues.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

<Production of DNA / chitosan complex>
Modification of salmon sperm-derived DNA (300 base pairs) using chitosan is performed by mixing a chitosan aqueous solution and a DNA aqueous solution.

(a) Solution / DNA solution used: Salmon sperm-derived DNA (300 base pairs, manufactured by Nichiro) is dissolved in distilled water. (5mg / 1ml)
Chitosan solution: Chitosan (molecular weight 130,000, manufactured by Nichiro) was dissolved in 50 ml of 0.2N HCl. 0.2N in this solution
NaOH and distilled water were gradually added to make 100 ml of pH 5 solution. (5mg / 1ml)

(b) Synthesis from chitosan aqueous solution and DNA aqueous solution The DNA aqueous solution was added to 100 ml of the stirring chitosan aqueous solution and allowed to react for 1 hour. The precipitate formed after the reaction was centrifuged. The obtained precipitate was washed with 60 ml of Tris-HCl buffer (10 mM, pH 7.2) (hereinafter referred to as Tris-HCl buffer) and centrifuged again. Washing with Tris-HCl buffer was performed twice. Next, after washing with 60 ml of distilled water, centrifugation was performed. Washing with distilled water was performed 3 times. The resulting white precipitate was lyophilized. The yield was 600 mg, and the molecular weight ratio of DNA / chitosan complex was 0.95 / 1 based on the determination of phosphorus.
When the concentration of the reaction product is changed in the above production method, that is, an aqueous DNA solution (7.5 mg / 1 ml) and an aqueous chitosan solution (2.5 mg / 1 ml) or an aqueous DNA solution (2.5 mg / 1 ml) and an aqueous chitosan solution ( 7.5 mg / 1 ml), the molecular weight ratio of DNA / chitosan complex was 1.28 / 1 and 0.88 / 1, and the yield was 700 mg and 300 mg.
When the kind of the buffer is changed in the above production method, the porosity and the pore diameter in the DNA / chitosan complex are different.
For example, a phosphate buffer (10 mM, pH 7.2, 0.9% NaCl) (hereinafter referred to as PBS buffer), a HEPES buffer (10 mM, pH 7.2), a Tris-HCl buffer or a borate buffer (10 mM). ,
The DNA / chitosan complex washed at pH 7.2) has a large number of pores and a large form. (Fig. 1 and Fig. 2)
If the molecular weight ratio of DNA / chitosan is different in the above production method, the porosity and the pore diameter in the DNA / chitosan reaction product will be different even when the same buffer solution is used. For example, a DNA / chitosan complex washed with a Tris-HCl buffer has a higher porosity when it has a lower DNA content. (Figure 3)

<Cytotoxicity of DNA / chitosan complex>
Mouse fibroblast L-929 cells were prepared at a concentration of 20,000 cells / ml, and each well of 96 wells was 0.1.
ml seeded. After 24 hours, the DNA / chitosan complex obtained in Example 1, the starting material DNA and chitosan powder were added to the culture solution (Eagle) at concentrations of 0.25 mg / ml, 0.5 mg / ml and 1 mg / ml. The MEM) was then diluted in order and the cells were exchanged and allowed to act on the cells for 2 days. Two days later, the cell survival rate was expressed as a percentage of the control (no sample added) group by the MTS method (FIG. 4).
The cell viability was clearly higher at any concentration in the DNA / chitosan reaction than in chitosan alone, suggesting no cytotoxicity.

<Animal experiment of DNA / chitosan complex>
Under ether anesthesia, the back skin of a 7 week old SD male rat was cut with a scalpel, and the DNA / chitosan complex obtained in Example 1 was immediately embedded in the subcutaneous tissue and sutured. At this time, an experiment in which chitosan alone was embedded, and only the skin incision in the back was added and sutured was performed simultaneously. On days 1, 3, 5 and 10 after the operation, the dorsal subcutaneous tissue was removed, fixed by immersion in 10% formalin for 2 days, embedded in paraffin as usual, and sliced and then stained with HE.
In the specimen 3 days after the operation, there was a clear difference in tissue reaction between the DNA / chitosan complex embedded group and the chitosan simple substance embedded group. That is, in the DNA / chitosan complex-embedded group, only a small amount of the complex remained in a part of the subcutaneous tissue and the reaction of the surrounding tissue was extremely weak (FIG. 5), whereas the chitosan-alone administration group However, a large amount of chitosan was still found in the subcutaneous tissue, and a large amount of leukocyte infiltration into the residual chitosan was observed at the same time, and the inflammation of the surrounding tissue was strong (FIG. 6).
Thereafter, in the DNA / chitosan complex implantation group, the condition recovered to the same state as that of the control group with only skin incision 5 days after the operation, whereas in the chitosan single implantation group, a considerable amount was obtained even 10 days after the operation. The chitosan residue was observed, and at the same time, it maintained the flammability of surrounding tissues.

<Intercalation and groove binding of DNA / chitosan complex>
Red doxorubicin, an anticancer agent, was dissolved in distilled water. (200 mg / ml) 3 mg of the DNA / chitosan complex obtained in Example 1 was added to this solution and reacted for 3 days. The absorbance (480 nm) of the reaction solution was measured to quantify the remaining amount of doxorubicin hydrochloride. As a result, the concentration of doxorubicin (8 mg / ml) in the reaction solution decreased, suggesting intercalation of doxorubicin hydrochloride. The red coloration of the DNA / chitosan complex was also confirmed with the naked eye. Similar results were obtained with other anti-cancer agents (actinomycin, daunomycin, daunorubicin, pirarubicin).

<Manufacture of medical materials using DNA / chitosan complex>
Medical materials differ in the required form and state depending on the treatment site and treatment method. The DNA / chitosan complex can be adjusted in form and condition in accordance with the therapeutic policy. For example, the DNA / chitosan complex obtained in Example 1 is poured into a Teflon ring (height 1 mm, inner diameter 5 mm) placed on a filter, filtered, and freeze-dried to form a disk shape. Therefore, a molded product of any form can be obtained by adjusting the form of the mold. Furthermore, the porosity can be adjusted by selecting a buffer solution. In addition, the DNA / chitosan complex washed with borate buffer or Tris-HCl buffer is placed in distilled water and stirred, so that it is easily suspended and exhibits fluidity. The DNA / chitosan complex in this suspension passes through the needle. Therefore, administration by a syringe is also possible.

Since the medical or dental material of the present invention is formed from a reaction product of DNA and chitosan and is very excellent in biocompatibility, it is a novel medical or dental material that can be widely used. Is provided. In particular, because of its characteristics, it is highly useful in the dental field and is suitable for use in the field of regenerative medicine, and is expected to be used in that field.

It is a photograph showing the state in which the porosity and the pore size in the DNA / chitosan complex are different when the type of the buffer is changed during the synthesis of the DNA / chitosan complex. In the figure, (a) is the HEPES buffer solution. (B) is a photograph showing the state of porosity and pore diameter when washed with a phosphate buffer solution (PBS buffer solution). It is a photograph showing the state in which the porosity and the pore size in the DNA / chitosan complex are different when the type of the buffer solution is changed during the synthesis of the DNA / chitosan complex. In the figure, (c) is the Tris-HCl buffer. (D) is a photograph showing the state of porosity and pore diameter when washed with a borate buffer solution. It is a photograph which shows the state from which the porosity and pore diameter differ by the DNA content in the DNA / chitosan complex wash | cleaned with the same buffer (Tris-HCl buffer solution). It is a graph which shows the measured value of the cell viability in the cytotoxicity test of DNA / chitosan complex. It is a photograph which shows the difference in the tissue reaction in the animal experiment of DNA / chitosan complex. It is a photograph which shows the difference in the tissue reaction in the animal experiment of the chitosan single administration group.

Claims (21)

A shaped product of a DNA / chitosan complex obtained as an electrostatic reaction product of DNA and chitosan, and the DNA forming the complex retains the double helix structure peculiar to DNA without breaking. A medical material and / or a dental material, wherein the composite is substantially free of water solubility. Non-shaped form of DNA / chitosan complex obtained by electrostatic reaction of DNA and chitosan, and the DNA forming the complex retains the double helix structure unique to DNA A medical material and / or a dental material, wherein the composite is substantially free of water solubility. The medical material and / or dental material according to claim 1 or 2, wherein the DNA forming the DNA / chitosan complex is natural DNA and / or synthetic DNA. The medical material and / or dental material according to claim 1 or 2, wherein the chitosan forming the DNA / chitosan complex has a molecular weight of 320 (glucosamine residue number 2) or more. A medical material and / or a dental material, wherein a low molecular weight compound having a molecular weight of approximately 300 to 1300 Da is included in the DNA / chitosan complex by intercalation and / or groove binding. The medicinal component, bone regeneration-inducing factor, fibroblast growth factor or tissue regeneration-inducing factor is intercalated and / or groove-bound to the DNA / chitosan complex shaped article, and the medicinal component, bone regeneration-inducing factor or fiber A medical material and / or dental material characterized in that a blast growth factor or a tissue regeneration-inducing factor is delivered and supplied. A non-shaped form of the DNA / chitosan complex is obtained by intercalating and / or groove binding a medicinal component into a dosage form of solution preparation, dispersion preparation, semi-solid preparation, granular preparation or molded preparation. A medical material and / or a dental material characterized by being formed. A dental material characterized in that an antibacterial agent is intercalated and / or groove-bound to an excipient comprising a DNA / chitosan complex to deliver and supply the antibacterial agent to an affected area or a necessary location. It is characterized in that an anti-periodontal disease agent is intercalated and / or groove-bound to an excipient comprising a DNA / chitosan complex to deliver and supply the anti-periodontal disease agent to an affected area or a necessary place. Dental material to do. Dentistry characterized in that an osteogenesis inducer is intercalated and / or groove-bound to a shaped article comprising a DNA / chitosan complex to deliver and supply the osteogenesis inducer to the affected area or a necessary location. Materials. It is a dental material such as a membrane, film, lining material or coating material produced by using an excipient comprising a DNA / chitosan complex and intercalating and / or groove-binding a drug or tissue regeneration-inducing factor. A dental material characterized in that the drug or tissue regeneration-inducing factor is delivered and supplied to an affected area or a necessary location. A dosage form of any one of a solution preparation, a dispersion preparation, a semi-solid preparation, a granular preparation or a molded preparation obtained by intercalating and / or groove-binding a medicinal ingredient into the non-shaped form of the DNA / chitosan complex. In order to produce medical materials and / or dental materials by adding them to the raw materials as additives, the medicinal ingredients are delivered and supplied to the affected area and necessary places via the dental materials. A medical material and / or a dental material characterized by the above. Intercalate and / or groove binding of a medicinal ingredient in a non-shaped form of DNA / chitosan complex to form any one of solution preparation, dispersion preparation, semi-solid preparation, granular preparation or molded preparation The raw material that is formed and added as an additive, primer, bonding agent, composite resin, temporary sealing material, back layer material, root canal filling material, periodontal dressing material, cement for bonding, direct bonding material, denture, rebase A dental material produced by manufacturing a dental material such as an antibacterial agent for materials and dentures, and delivering and supplying the medicinal component to an affected area or a necessary location via the dental material. A hydroxyapatite structure is formed by using a phosphate residue contained in a scaffold for regenerating bone tissue and periodontal tissue using a DNA / chitosan complex shaped material and transplanted. A regenerative medical material and / or a regenerative dental material, wherein a bone tissue or periodontal tissue is regenerated by forming a lime compound, depositing a lime compound, or serving as a bone supplement carrier. A scaffold formed by using an excipient comprising a DNA / chitosan complex, wherein a hydroxyapatite structure is formed in the scaffold using a phosphoric acid residue contained by transplantation. Regenerative dental material characterized by. A membrane formed by using an excipient comprising a DNA / chitosan complex, wherein a hydroxyapatite structure is formed on the membrane by using a phosphoric acid residue contained by transplantation. Regenerative dental material. A tooth surface covering material formed using a DNA / chitosan complex, which is characterized in that a lime compound is deposited on the surface of the covered tooth to promote tooth remineralization. Regenerative dental coating material. A film, a lining material, a coating material, a dressing material or artificial skin is formed using an excipient comprising a DNA / chitosan complex, and this is used to coat a medical material and / or a dental material, thereby implanting the film. A medical material and / or a dental material characterized in that the biocompatibility at the time of improvement is improved, or a biological reaction to a foreign substance in a living body is suppressed. A method for preparing a medical material and / or a dental material, characterized in that a DNA / chitosan complex is prepared in which the form and shape of a reaction product obtained by reacting DNA with chitosan and washing with a buffer solution are prepared. . If necessary, a buffer for washing the reaction product of DNA and chitosan, Tris buffer, borate buffer, HEPES buffer, acetate buffer, citrate buffer, glycine buffer, barbiturate buffer, Phthalate buffer, cacodylate buffer, carbonate buffer, Bis-Tris buffer, Bis-Tris-propane buffer, MES buffer, ADA buffer, PIPES buffer, ACES buffer, collamine chloride buffer, Select from BES buffer, MOPS buffer, TES buffer, HEPPS buffer, Tricine buffer, glycinamide buffer, Bicine buffer, TAPS buffer, CHES buffer, CAPS buffer, phosphate buffer, etc. The method for preparing a medical material and / or a dental material according to claim 19, wherein the method is prepared. A medical material characterized in that a DNA / chitosan complex is put into a borate buffer solution to form a fluid suspension, and the fluid suspension is molded into an arbitrary shape. Or a method for preparing dental materials.