BONE BINDER FOR PREVENTING OR TREATING PERIODONTAL DISEASE DERIVED FROM MUSSEL ADHESIVE PROTEIN, AND METHOD FOR PRODUCING SAME
The present invention refers to drug loading, the refractive index - Fe (III) complexes based on recombinant adhesive protein for prevention or treatment of periodontal disease using a bone binder and manufacturing method are disclosed. In addition, bone support including said bone binder are disclosed. In conventional tooth disease exerts the pin is periodontal disease. According to the report of the pseudo will only respond to at least 80% of adult our country is fitted with gum bottle it other. Periodontal disease can gastrointestinal disease, lipid metabolic disorders such as stroke and consequently Serial, etc. that a correlation indirectly reported. This is one cause of periodontal disease cannot cause complex indicated by the conventional advance order receipt described can be called the number of chronic diseases. Gingivitis and including a tooth support tissue caused by inflammatory conditions as a oral bacterial periodontal disease, bleeding, a pin portion of formation and destruction of alveolar bone loss that results due to the proximity of the patient's disease are disclosed. Such bacterial colonization periodontal disease, periodontal tissue penetration and periodontal tissue destroyed at the flowing of bacteria and the processing advances. Specifically, resulting from poor oral hygiene oral bacteria form in blood after the film is formed on the inflammation occurs in the event of bacteria often gums to be assembled, the air gap between the teeth and gums further this state 3.1 deeper pin portion in order to form a pixel, the drain pan oral bacteria that cause periodontal disease herein is generated. The air is weak stimulation such as gums or oral airway and blood even in a size slightly larger than the lower, and acute inflammatory pain is often altered causing substrate. This inflammation is lowered and performs the function of generating bone, bone is destroyed and ultimately increasing absorber is becoming an alveolar bone loss is equal to tooth of the boundary. Field of dental materials before the world market scale participates in the field increases, this increased population according to cope increasing demand dental materials are disclosed. By periodontal disease requiring transplantation old age population increases alveolar bone graft material growing demand of the electric light from the light source are disclosed. Dental bone graft material is filled with weakling of physical defect area, used in a dental material for promoting bone formation, bone graft material is heterogeneous among all animal or other living bone graft material (bone graft material) derived from indicating other. Bone graft material at the sites where the implanted bone binder and does not move, various implant are bone cells or peripheral region formed on growth of bone growth factor that they to and n is an integer. However, in accordance with the state of bone and bone density is low or poor patient bone such as the bone where the bone transplantation of high error rate is shifted disclosed pour disclosed. Until now the deviation of the bone graft material coating, binder 'blocking' instead of 'bond' for induction of bone formation cells serves primarily use different-sized preforms, surgery on the strength and number 2 difference when his present point number to die surface large aspect ratios door. In particular, use in implant, high viscosity polymeric material binder present in the mouth in a fast moisture since its effect is insufficient number of the doors is coupled with the flow tides. Thus, the fresh air is poor bone implant procedure can function successfully accomplished in executing the development of bone binder etc. required. The present invention automatically change searching for the victims of the dental bone binder, drug loading, the refractive index - Fe (III) complexes based on recombinant adhesive protein including excellent bone biocompatible binder, number and rate of drug loaded [...], since strong bone adhesion, then in the prevention or treatment of periodontal disease, which can be useful for identifying a patient bone disease is poor confirms, the arrears of work the present invention. Thus, the present invention refers to recombinant adhesive protein and a drug including, for prevention or treatment of a periodontal disease bone binder and manufacturing method under public affairs number broadcast receiver. In addition, the present invention refers to said binder including bone, bone support under public affairs number broadcast receiver. In addition, the present invention refers to said binder or said bone support including bone, implant kit number under public affairs broadcast receiver. In order to achieve said purposes such as, The present invention refers to Recombinant adhesive protein and a drug including, for prevention or treatment of periodontal disease bone binder number under public affairs substrate. In addition, the present invention refers to said manufacturing method for prevention or treatment of a periodontal disease bone binder number under public affairs substrate. In addition, the present invention refers to said binder including bone, bone support number under public affairs substrate. In addition, the present invention refers to said binder or said bone support including bone, implant kit number under public affairs substrate. Hereinafter, the present invention is described therein that are directionally. The present invention refers to Recombinant adhesive protein and a drug including, for prevention or treatment of periodontal disease bone binder number under public affairs substrate. Said recombinant adhesive protein is derived from recombinant adhesive protein, preferably [...][...] (Mytilus edulis), the multiplier [...][...][...][...] (Mytilus galloprovincialis) or derived from recombinant adhesive protein or a variant thereof (Mytilus coruscus) include, the number is not one. Said recombinant adhesive protein is preferably converted into the tyrosine residues catechol compounds, catechol compounds converted into the entire tyrosine residues is preferably 10 - 100%. In an amino acid sequence tyrosine occupies about 1 - 50% of the residents most recombinant adhesive protein implementation being. Recombinant adhesive proteins via catechol compound is added to the refractive index of tyrosine hydration can be converted into OH (DOPA). However the recombinant adhesive protein produced in e. coli is not converted are tyrosine, L-tyrosine in a waveguide by converting enzyme and chemical treatment method of performing a modified preferably. Recombinant adhesive protein tyrosine residues known method included in modifying contrast method using a steel number one waveguide is not. Said catechol compounds including the compound id rock time under D, crosslinked through recombinant adhesive protein adhesion action imparting compound big. Specifically, waveguide (3,4 non-dihydroxyphenylalanine, DOPA), waveguide quinone (Dopa-O-quinone), toe group (2, 4, 5 provided trihydroxyphenylalanine, TOPA), like toe group quinone (Topa quinone) and their derivatives may be, preferably a refractive index. The catechol compound capable of forming a complex comprising a metal and said metal organic - catechol compound can be produced. (DOPA)- Fe (III) preferably said catechol compound - metal composites of the waveguide can be a composite. (III) coordinating said recombinant adhesive protein present in crosslinked through bonds to the formation of the refractive index and Fe, Fe (III) and the refractive index into our body since the pin is already present biocompatible substances respectively. Said metal is any metal capable of coordinating catechol compound, typically be a metal or transition metal. Example, said metal coordinating couplable iron (iron), titanium (titanium), vanadium (vanadium), chromium (chrome), manganese (manganese), cobalt (cobalt), Ni (nickel), zirconium (zirconium), niobium (niobium), Mo (molybdenum), technetium (technetium), ruthenium (ruthenium), Rh (rhodium), palladium (palladium), is (silver), hafnium (hafnium), tantalum (tantalum), tungsten (tungsten), rhenium (rhenium), osmium (osmium), iridium (iridium), and gold (gold) can be like platinum (platium), iron (III) preferably in. Said recombinant adhesive protein is preferably (a) sequence number 4 consisting of the amino acid sequence of polypeptide, (b) a polypeptide consisting of the amino acid sequence of sequence numbers 5, 6 (c) sequence number of 1 to 10 amino acid sequences of polypeptides (a) (d) said polypeptide and connected twice successively, (b) (c) of polypeptides and said at least one selected from the group consisting of polypeptides consisting of 2 be a fusion polypeptide. (C) said limited but preferably sequence number 7 in polypeptides may be not be a polypeptide consisting of the amino acid sequence of. (D) in addition said polypeptide fused in sequence numbers 1 or sequence number 3 is supported by but preferably not limited to be a polypeptide consisting of the amino acid sequence of. In the present invention recombinant adhesive protein variants (mutants) is desirably recombinant adhesive protein adhesion of said recombinant adhesive protein carboxylic acids or amino end group content in the number before maintaining luck thread end in that it provides additional sequence or a portion of amino acids can be substituted with another amino acid. More preferably said recombinant adhesive protein carboxylic acids including 3 to 25 amino acids polypeptides of a RGD luck thread end or amino end is connected to a count of the number of tyrosine residues may be recombinant adhesive protein forms 100% 1, 3, 4 - dihydroxyphenyl - L - alanine (DOPA) is preferably 5 to 100% may be substituted. Said RGD amino acid including 3 to 25 a limited but preferably not RGD (Arg Gly Asp, sequence number 8), RGDS (Arg Gly Asp Ser, sequence number 9), RGDC (Arg Gly Asp Cys, sequence number 10), RGDV (Arg Gly Asp Val, sequence number 11), RGDSPASSKP (Arg Gly Asp Ser Pro Ala Ser Ser Lys Pro, sequence number 12), GRGDS (Gly Arg Gly Asp Ser, sequence number 13), GRGDTP (Gly Arg Gly Asp Thr Pro, sequence number 14), GRGDSP (Gly Arg Gly Asp Ser Pro, sequence number 15), (Gly Arg Gly Asp Ser Pro Cys, sequence number 16) and YRGDS GRGDSPC (Tyr Arg Gly Asp Ser, sequence number 17) consisting of at least one selected from the group consisting 1 be a. A RGD luck thread end or amino end of said recombinant adhesive protein carboxylic acids including 3 to 25 amino acids connected recombinant adhesive protein variants of the polypeptides not limited but preferably the sequence numbers 2 be a polypeptide consisting of the amino acid sequence of. Said recombinant adhesive protein limited but preferably not to contain a conventional gene expression vector which can express it became work external number to a distal portion, and mass-production method can be a genetically engineered. Said vector produced which can be appropriately selected according to the type of host cells for the and or, work percentage be new number. Said vector transformed host cells producing recombinant protein from the transformant method hereinafter to conventional method embodiment for the method can. Selection of said vector, small number, such as transformation and expressing recombinant protein in the method, the embodiment of the present invention is provided to hereinafter for if one skilled can, conventional method to deformation activated in the present invention multiple myelomas are included. Said antibacterial number number or anti-inflammatory drug or combinations thereof may be, the number one are not disclosed. Number said antimicrobial is chlorhexidine, [...] process, diamino cyclin, tetracycline, as antiprotozoal [...], of vancomycin, [...], phosphor feed, [...], pro [...], cancerous blood thread phosphorus, penicillin-resistant Streptococcus pneumoniae, killing by poisoncycle phosphorus, as antiprotozoal it will be born in the mote, cephalosporin, nor car D new, gentamicin, erythromycin neohesperidin dihydrochalcone, republic of Ghana feed, yeast, roh Eamerican crow lysine, amino car new, assimilable lama capsaicin, d hemp cloth car new, [...] cells, into cephalosporin, erythromycin, [...] cycle, memory where, to the jade it lived, such as methicillin-and backsightdick it buys width implementation being. Preferably said number dental field to the antimicrobial is chlorhexidine, [...] process, diamino cyclin, tetracycline, as antiprotozoal [...], etc. be of vancomycin. Said acetoacetoxy-functional amine pen number is anti-inflammatory, aspirin, ibuprofen, with lung pleasure decrypts, indomethacin, piroxicam, lung Roh pro pen, [...], process for producing ketoprofen, [...], soupwith pen, method for preparing, [...], such as [...] implementation being. Which is provided as a scenic beauty said periodontal disease can, bottle along (gingivitis) or oral (periodontitis) degree of gingivitis implementation being. In the form of periodontal disease is gingivitis or restoring relatively lightweight with fast gums i.e., soft tissue only limited shape it is, gums and gum when used for such inflammation to periphery bone suitable for a oral. Said bone binder shutter apparatus bone, upper jaw, mandible angle, evil joint, such as alveolar bone or a pin portion can be adhered to. 1% to 50% by weight based on the total weight of said contrast bone binder thereby recombinant adhesive protein, as well as applies a jawbone bone or gums like water can exhibit good adhesion. In addition, drug release said bone binder be [...] number. In the embodiment of the present invention according to one, bone binder gel, hydrogel or of electrospun fibers to form number elder brother anger, swell properties and drug release can. In addition, the present invention refers to said manufacturing method for prevention or treatment of a periodontal disease bone binder number under public affairs substrate. Said bone binder gel, hydrogel, fiber, powder, cream, pack, sheet, oils and the like and can the number elder brother anger, preferably gel, hydrogel, fibers elder brother anger number can be disclosed. Said gel number may be (1) recombinant adhesive protein, drug and containing xanthan gum having per dissolving solvent mixture; and (2) heating said 30 provided 50 °C mix solution in 20 - 30 hours; number including 1308. bath. At this time, said recombinant adhesive protein 0. 1 - 10% by weight, drug 0. 1 - 10% by weight and a thickening 0. 1 - 10% by weight preferably including a. Said hydrogel number may be (1 ') recombinant adhesive protein, drug, vinylpyrrolidone (vinyl prrrolidone) and meta [...] (methacrylate) dissolving a mixture of solvent; (2') AIBN (azobisisobutyronitrile) without further application in said mixed solution and then polymerizing and cross-number 40 provided 80 °C, washed methanol; and (3') in 2 - 4 days drying said cleaning polymer 30 provided 50 °C; bath including number can be disclosed. EGDMA cross-linking said number is (ethyleneglycol dimethacrylate), photoresist mote, hydroxyphenyl acetic acid, hydroxy propionic acid, dopamine, epitaxial general, hydroxyethyl aniline can be etc., preferably EGDMA can be using. Said number may be electrospun fibers (1 ") recombinant adhesive protein, drug, poly gamma glutamic acid (polygammaglutamic acid, a Γ-pGA) hyaluronic acid and dissolving solvent mixture; and (2") said electrospun mix solution step; bath including number can be disclosed. Said electrospun conditions include voltage 8 provided 25kV, radiation distance of 5 a-20cm and syringe pump fluid velocity 0. 2 a-5ml/h conditions can be performed. The number of solvent containing said number of the bath can be used which are not specially number it became grudge, distilled water, process [...] (hexafluoroisopropanol), styrene thermoplastic rubber (trifluoroacetic acid), dimethylformamide amide (dimethyl formamide), dimethyl sulfoxide (dimethyl sulfoxide), TFE (trifluoro ethylene), acetone (acetone), MC (methylene chloride), THF (tetrahydro furan), acetic acid (acetic acid), formic acid (formic acid) can be use. In addition, the present invention refers to said binder including bone, bone support number under public affairs substrate. Said bone support can be bioactive material. Said bioactive material is anti-inflammatory, antioxidant or the creation which boils a natural and artificial material disclosed. In one example, nano hydroxyapatite, gold nanoparticles, peptide, enzyme, transcription factor, small molecule drug, liposome, nucleotide, toxin, antigenic peptides, antibody, hormone, carrier protein, immunoglobulin, structural protein, a motor function protein, receptor, signal (signaling) protein, a seed storage protein, membrane protein, protein trans-membrane (transmembrane), internal (internal) protein, external (external) protein, secreted protein, viral protein, congenital (native) protein, protein per, cutting protein, protein having disulfide bonds, protein complex, chemically modified protein, prion (prions), and antibody fragment selected from the group consisting preferably 1 species and, preferably nano hydroxyapatite the driving circuit board. In addition the present invention refers to said binder or said bone support including bone, implant kit number under public affairs substrate. The present invention according to drug loading - catechol compound contains a metal coordination complexes including bone as well as biocompatible binder, and drug release number [...], exhibit excellent bone adhesion, this invention can be useful for bone implant patient...copyright 2001. The present invention according to the drug loaded catechol compound - bone binder metal coordination complex, - Fe (III) complexes based on recombinant adhesive protein in particular using bath so that the refractive index number, which is excellent in biocompatibility, number and rate of drug loaded [...], since strong bone adhesion, then in the prevention or treatment of periodontal disease, useful for bone disease is poor patient taking can be equal to or less than. Also in the embodiment 1 according to Figure 1 shows a result of a FP-a 151 recombinant recombinant adhesive protein RGD representing an Image of sDS-a pAGEdry width in hot water heater are disclosed. Figure 2 shows a number of gel (gel) also including a drug release number for lengthening the FP-a 151 in the embodiment 2 - 1 according to RGD trillion processes indicative disclosed. Figure 3 shows a UV gel including a drug release number for lengthening the FP-a 151 also in the embodiment 2 - 1 according to RGD components is are disclosed. Figure 4 shows a gel including a drug release number for lengthening the FP-a 151 in the embodiment 2 - 1 according to RGD also exhibiting a solution are disclosed. Figure 5 shows a number for lengthening its gel time according to a drug release including a FP-a 151 also in the embodiment 2 - 1 according to RGD chlorhexidine release indicating an amount are disclosed. Figure 6 shows a including a FP-a 151 in the embodiment 2 - 2 according to RGD swelling representing a hydrogel (swelling ratio) also are disclosed. Figure 7 shows a including a drying time according to the FP-a 151 in the embodiment 2 - 2 according to RGD hydrogel swelling representing (swelling ratio) also are disclosed. Figure 8 shows a plasma processing according to the FP-a 151 including also in the embodiment 2 - 2 according to RGD swelling representing a hydrogel (swelling ratio) are disclosed. Figure 9 shows a the FP-a 151 including a hydrogel exhibits cell toxicity in the embodiment 2 - 2 according to RGD also are disclosed. Figure 10 shows a representative of the Image that the FP-a 151 in the embodiment 2 - 3 according to RGD also including a optical of electrospun fibers are disclosed. Figure 11 shows a scanning electron microscope (SEM) in the embodiment 2 - 3 according to RGD also that the FP-a 151 including a representative of the Image of electrospun fibers are disclosed. Figure 12 shows a the FP-a 151 in the embodiment 2 - 3 according to RGD also including a cohesion of electrospun fibers exhibiting disclosed. Also in the embodiment 3 according to Figure 13 shows a nano hydroxyapatite (nano - HA) fixed to the support surface (a) SEM Image and (b) the bone bone support fixed surface representative of the Image of hydroxyapatite nano SEM are disclosed. Figure 14 shows a bone surface also in the embodiment 3 according to nano hydroxyapatite (nano - HA) fixed to the support number XRD measurement result of XRD measurement results in transmission (purchase from bio-a oss) article contains regulated compared are disclosed. Also in the embodiment 3 according to Figure 15 shows a bone support according to (a) nano - HA fixed surface scanning electron microscope (SEM) Image and (b) compressive strength porosity exhibiting disclosed. Hereinafter, preferred embodiment of the present invention to aid in understanding a number etched. In the embodiment of the present invention is more easily understand to however only for being ball number, in the embodiment of the present invention content is restricted by are not correct. In the embodiment 1. - Preparation of the refractive index (DOPA) containing recombinant recombinant adhesive protein (rGD-a fp151) First, recombinant adhesive protein (sequence number 1) natural that the FP-a 151 present recombinant adhesive protein that the FP-a 1 (Genbank No. Q27409) connected in an amino acid sequence consisting of 6 times a FP-a 1 (Mytilus mussel foot protein type 1) variants (AKPSYPPTYK) compositions containing the synthesized signal, the FP-a 1 of 2 mgfp provided 5 between variants of gene (Genbank No. AAS00463) after inserting, number e. coli was high pressure liquid coolant. The number of said recombinant adhesive protein that the FP-a 151 equal number patent disclosure WO2005/092920 station sol shown, multiple myelomas are included herein with reference to the movement of the patent document. Said number of carboxyl end (C end) RGD (Arg Gly Asp) prepared by the recombinant adhesive protein that the FP-a 151 including a number to a high pressure liquid coolant by recombinant adhesive protein rGD-a fp151 his soft amino acid deficiency. Then, number it is sour with the mote ((mushroom tyrosinase, SIGMA) (in vitro) to conduct an enzymatic reaction in vitro using enzymes, DOPA (dihydroxyphenylalanine) was converted into the FP-a 151 said recombinant adhesive protein RGD of tyrosine residues. Specifically, 1. The FP-a 151 a number of RGD it is sour with the mote of 100 μg/mL solution and 50 mg/mL buffer solution (100 mm sodium phosphate, 20 mm boric acid, 25 mm ascorbic acid, pH 6. 8) in time by reacting 1, 1% acetic acid solution was dialysis. Recombinant adhesive protein RGD amino acid composition analysis of a FP-a 151 for efficiency analysis for repairing a result, about 50% of the entire it is sour with the mote DOPA residue number that is converted formate, purity 90% or more DOPA - sDS-a pAGE (Sodium Dodecyl Sulfate Polyacryl Amide Gel Electrophoresis) containing recombinant recombinant adhesive protein having performed result schedulable number has been confirmed that the high pressure liquid coolant. In addition, Fe (III) complexes for - DOPA under trillion number, said DOPA - recombinant recombinant adhesive protein solution containing FeCl3 The solution to the Fe: DOPA is 1:3 mixing ratio by molar (molar), Fe (III)- containing recombinant recombinant adhesive protein RGD number that the FP-a 151 - DOPA was a high pressure liquid coolant. Said in the embodiment 1 according to the FP-a 151 of recombinant recombinant adhesive protein RGD Image of the sDS-a pAGE results and freeze dry width 1 also shown. In the embodiment 2. Recombinant adhesive using the protein drug release number for lengthening bone binder number bath 2 - 1 including a number of bath gel number that the FP-a 151 RGD recombinant adhesive protein A high pressure liquid coolant in said in the embodiment 1 using a gel (gel) drug release number for lengthening the FP-a 151 RGD number number was high pressure liquid coolant. First distilled water (0. 2 mg/mL) RGD recombinant adhesive protein dissolved in the FP-a 151 0. 5 wt %, a thickening 2. 0 wt %, 1 [...] (chlorhexidine dihydrochloride). 0 wt % to 20% is dissolved in distilled water and a [...] 1. 0 wt % distilled water 95. 5 wt % was mixed selectively. Then, mix solution which is pre-heated in said 40 °C (annealing) performed after annealing in an oven 24, 7 by gelling-gate maintained at room temperature. The FP-a 151 including a drug release number to number 2 shown also trillion processes gel for lengthening said in the embodiment 2 - 1 according to RGD. 2 - 2 bath including a number of hydrogel number that the FP-a 151 RGD recombinant adhesive protein A high pressure liquid coolant in said in the embodiment 1 number using a high pressure liquid coolant hydrogel (hydrogel) drug release number for lengthening the FP-a 151 RGD his number. First deformation (methyl methacrylate, MMA) organic solvent is methyl meta [...] for number, into a 50 ml MMA and 50 ml NaOH the separating in the atmosphere which it will peel has surpassed its lower after mixing, after which the process embodiment 3 times lower was again mixed with distilled water. Then, a stand-alone number place MgSO to moisture4 Adding a small amount of have, his vacuum distilling. Positive number bar code input mode using the MMA into his sealing kit rate. (MMA) and vinyl pyrrolidone (VP) is a positive number said methyl methacrylate [...] (w/w %) mass ratio of 1:99 and reduces, the disclosure number AIBN 0 positive number. 2 wt %, crosslinked number EGDMA 0. The FP-a 151 when blended with solution 2 wt % and recombinant adhesive protein RGD number have high pressure liquid coolant, nitrogen atmosphere to 60 °C 24 was polymerized while in same time. After washing the product with methanol (MeOH) tracks, including a vacuum in an oven preheated during 40 °C 3 RGD followed by drying the FP-a 151 number hydrogel was high pressure liquid coolant. In addition, the separated from each other, said mixed solution [...] solution after mixing, said polymerization process including a high pressure liquid coolant by RGD hydrogel drug release number for lengthening the FP-a 151 embodiment his number. 2 - 3 that the FP-a 151 including a number number bath of electrospun fibers RGD recombinant adhesive protein Using a high pressure liquid coolant in the FP-a 151 RGD number said in the embodiment 1 (fiber) was electrospun fibers drug release number for lengthening a number high pressure liquid coolant. A first recombinant adhesive protein RGD [...] process to completely dissolve the FP-a 151 (Hexafluoroisopropanol, HFIP) after stirring 2 provided 15wt % solvent, solvent by selectively applying further styrene thermoplastic rubber (Trifluoroacetic acid, TFA), recombinant adhesive protein RGD number that the FP-a 151 solution was high pressure liquid coolant. Similarly. Poly gamma glutamic acid (Polygammaglutamic acid, a Γ-pGA) process to completely dissolve a [...] (Hexafluoroisopropanol, HFIP) after stirring 2 provided 15wt % solvent, solvent by selectively applying further styrene thermoplastic rubber (Trifluoroacetic acid, TFA), number of Γ-pGA solution was high pressure liquid coolant. In addition. Hyaluronic acid (Hyaluronic acid) process (Hexafluoroisopropanol, HFIP) completely dissolving solvent to a [...] 2 provided 15wt % hyaluronic acid solution was stirring number high pressure liquid coolant. Then, a high pressure liquid coolant said number i) recombinant adhesive protein solution, ii) of Γ-pGA solution, and iii) each hyaluronic acid solution (1 - 98% / 1 - 98% / 1 - 98%) ratio after mixing, aluminum foil was electrospun above same. In addition, the separately, adding said mixed solution [...] uniformly blended solution electrospun-gate. Process factor include voltage 8 provided 25kV, radiation distance 5 provided 20cm, syringe pump fluid velocity of 0. 2 a-5ml/h made from fixed, 17 a-23G size needle (needle) was used. In a resulting nanofiber rule aluminum foil after upside down, sealing his rate. In the embodiment 3. The FP-a 151 based bone binder including bone support number bath RGD recombinant adhesive protein High pressure liquid coolant in said in the embodiment 2 that the FP-a 151 based bone binder and bioactive materials including number mussels adhesive protein RGD bone support number was high pressure liquid coolant. First, porcine bone graft material and high pressure liquid coolant in the mixed bone number said in the embodiment 2, PVB (polyvinyl butyral) dispersion number further after mixing in TEP (triethyl phosphate) in number and binder, ethanol (EtOH) with respect to the solvent. Then, have complex for preparing said slurry layer is formed, polyurethane sponge into the same mold, a stand-alone number after excess slurry, drying the bone support number was high pressure liquid coolant. Then, said number prepared by the bone support bio-active nano hydroxyapatite (nano hydroxyapatite) solution, followed by drying, nano hydroxyapatite (nano - HA) number was fixed bone support surface high pressure liquid coolant. Experiment example 1. Recombinant adhesive using the protein drug release number for lengthening analyzing characteristic of bone binder 1 - 1 that the FP-a 151 including gel characterizing a RGD recombinant adhesive protein In the FP-a 151 a number including measuring the spectrum UV gel drug release number for lengthening said in the embodiment 2 - 1 have a high pressure liquid coolant RGD. Shown also in comparison with the same contrast of the troop claw site (closite) 3. Also as shown in the 3, including UV gel of the present invention drug release number for lengthening [...]silver UV spectrum shown in an almost similar contrast aspects of the troop claw site spectrum. In addition, a number including a high pressure liquid coolant in the FP-a 151 RGD drug release number for lengthening said in the embodiment 2 - 1 by using a viscometer Brookfield viscosity gel have, compared with the same contrast of the troop claw site (closite) (periocline) to peripheral oak phosphorus 4 also shown. As shown in the variation also 4, of the present invention drug release number for lengthening the viscosity of a gel (RGD micelle by the FP-a 151) 2. 45 Pa s it-1 Exhibit, matching of the troop claw site (closite) of 2. 53 Pa s it-1 Represents the value similar to a sliding, peripheral oak phosphorus 24. 81 Pa s it-1 In order low value compared and viscoelasticity. However, recombinant adhesive protein RGD when adding the FP-a 151, DOPA - containing rGD-a fp151 (1. 5 mg) is 2. 92 Pa s it-1 , And Fe (III)- DOPA - containing rGD-a fp151 (1. 5 mg) is 2. 93 Pa s it-1 Exhibit improved viscosity can be boosted. In addition, a number said in the embodiment 2 - 1 including a high pressure liquid coolant in the FP-a 151 for measuring drug release number for lengthening its RGD [...] for release from gel, 37 °C dialysis in performing, at a wavelength of 254 nm absorption spectrum caused by every predetermined time 24 sample were measured. Shown also in comparison with the same contrast of the troop claw site (closite) 5. As shown in the variation also 5, of the present invention drug release number for lengthening of the troop matching gel contains substantially similar drug release amount per hour (closite) claw site can be known. 1 - 2 that the FP-a 151 including hydrogel characterizing a RGD recombinant adhesive protein The FP-a 151 including a high pressure liquid coolant in said in the embodiment 2 - 2 a RGD (swelling ratio) determined the number swelling hydrogel. A PBS (phosphate buffer saline) in a solution of water and a FP-a 151 including hydrogel dried RGD adding each, 24, 48 and 72 hours immersion-gate. A stand-alone water after excess number, have substitute with gelhigh weighing, also shown is the results of 6. The swelling degree was defined as follows. swelling (Sw)=[(Wt - Wd)/Wd], The swollen hydrogel is in such a time t Wt, dried hydrogel exhibits Wd is weight. As shown in the 6 also, hydrogel swelling degree solvent is water or PBS room substantially according difference, after immersion in addition time from the time of time between 24 72 almost similar values shown. The FP-a 151 a number including a high pressure liquid coolant in said in the embodiment 2 - 2 RGD (swelling ratio) were measured over time swelling hydrogel drying. Drying in a vacuum oven preheated 40 °C have performed 1 - 4 days, after dipping time and 48 each desiccator dried weight and at the time ruler surge swelling degree 24 were measured. The results of the 7 is also shown. Also as shown in the variation 7, drying time increases from the lowest 3 drying swelling degree hydrogel exhibiting a multivalent saturated represents the value too soon. The solvent substantially the water or PBS representing the difference didn't. In addition, after a maximum in swelling degree 24 after immersion was achieved. A number including a high pressure liquid coolant in said in the embodiment 2 - 2 RGD (swelling ratio) were measured according to the FP-a 151 swelling hydrogel treatment. 15 minutes in plasma have performed 50, 150, 250W, dried after dipping swelling degree desiccator 24 weight and at the time ruler line were measured. Also shown is the results of 8. As shown in the variation also 8, hydrogel swelling degree finish controls as compared to plasma, plasma treatment is large group representing the difference experiments a gate and, as a result from plasma processing by a swell of hydrogel into each can be increased, The FP-a 151 a number in a high pressure liquid coolant RGD hydrogel including said in the embodiment 2 - 2 cytotoxic were measured. First cell culture media hydrogel 24 hours after treatment, cell culture medium processing unit located either hydrogel NIN3T 3, him as 24 hours. Then, MTT cytotoxic using evaluating [...] have, also shown is the results of the 9. As shown in the variation also 9, cell survival rate matching of the troop hydrogel with nothing control army hydrogel processing group when compared do not show a big difference came, 90% or more cells have shown survival rates. As a result from the hydrogel of the present invention can be known low cytotoxicity. 1 - 3 that the FP-a 151 including analyzing characteristic of electrospun fibers a RGD recombinant adhesive protein A number including a high pressure liquid coolant in said in the embodiment 2 - 3 optical images of electrospun fibers 10 characterized in that it has also shown that the FP-a 151 RGD, scanning electron microscope (SEM) Image 11 is also shown. Also as shown in the 10 and 11 also, a FP-a 151 including a RGD electrospun fibers because of nano fiber aggregate has a high specific surface area, can be that of a 3 dimensional porous nonwoven fabric structure. In the FP-a 151 a number including a high pressure liquid coolant RGD said in the embodiment 2 - 3 was assessed cohesion of electrospun fibers. First, each 0. 25g implantation it boils re- sample and 1 cm × 2 cm size of electrospun sample after 400 μL saline, they been vertically and the opening and closing of cold and hot water. The results of the 12 is also shown. As shown in the variation also 12, through the opening and closing of the electrospun fibers fallingimplantation it boils re- sample with identifying lifts have, as a result from strong cohesion can be know implantation it boils re- to face of electrospun fibers. Experiment example 2. Analyzing characteristic of bone support 2 - 1 morphological and structural characteristic analysis Said in the embodiment 3 according to nano hydroxyapatite (nano - HA) fixed to the support surface (a) SEM Image and (b) the bone bone support fixed to SEM Image of hydroxyapatite nano surface 13 also shown. As shown in the variation of Figure 13 (a), of at least about 400 μm pore size of the bone support, porosity is 74. 17 ± 0. 43% 24.4, independent pores have been shown most almost no interconnected porosity. As shown in the variation in addition of Figure 13 (b), the thickness of about 15 μm bone surface of a support which is fixed to a becomes uniform nano hydroxyapatite (nano - HA) has been confirmed. High pressure liquid coolant in said in the embodiment 3 number nano hydroxyapatite (nano - HA) bone surface fixed to the support transmission number XRD measurement results compared to 14 also shown in article (purchase from bio-a oss) regulated. As shown in the variation also 14, representing the result of measurement of the present invention characterized in that it has the same XRD regulated bone support bone support, the same nano hydroxyapatite (nano - HA) structure can be beat. 2 - 2 water analysis High pressure liquid coolant to the support surface in said in the embodiment 3 number nano - HA fixed bone have analyze the contents of heavy metals by means of ICP analysis, the results of table 1 is shown. Wherein, N. D cannot be holds, MDL big detection limit. As shown in the table 1, (As, Cd, Pb and Hg) component of the present invention additional bone support substantially not detected can be the lower electrode. 2 - 3 mechanical properties analysis First, a bone support porosity (P) by the formula (1) and (2) according to the bill. (1) Db (g/cm3)=M (cm3)/V (g) (2) P (%)=(1 a-decibel/Dth) x 100, wherein P is porosity, bulk (bulk) density is Db, Dh is the theoretical density, mass M, V is volume and exhibits. In addition, bone support of compression strength formula (3) according to the bill. (3) K=4F / π d2 , Is in the center of the peak load (N) wherein F crush, the center of the diameter d (mm) is by a goniophotometer. (A) fixed bone support surface said in the embodiment 3 according to nano - HA scanning electron microscope (SEM) Image and (b) compressive strength according to porosity to 15 also shown. (A) of Figure 15 as shown or, when porosity 68% hereinafter independent material for reduced amount of interconnected porosity is formed as in the picomolar. In addition, as shown in the variation of Figure 15 (b), MPEG 2 strength porosity decreases stepwise increasing trend of. Consequently, products produced thereby increased compressive strength but reduced porosity 29 formed independent pores interconnected porosity results have shown the amount of reduced. Table 2 porosity according to compressive strength to support bone of the present invention have shown. From the results of the present invention to have the bone support and said highly development, excellent compression strength can be know. 2 - 4 - non cytotoxic evaluation High pressure liquid coolant to the support surface in said in the embodiment 3 nano - HA number fixed bone non - cytotoxic test was assessed. First, the food additive composition as well as the bone support 4g heater 20 ml saline and be used in the eluted under the test fluids. Then, L-a 929 cell culture cells based on conducting the evaluation experiments. 37 °C in 5% CO2 10% fetal bovine serum (v/v) and 95% air moist atmosphere (FBS; Invitrogen) L-a 929 cells, 50 μg/mL penicillin-resistant Streptococcus pneumoniae (Sigma Aldrich) 50 unit/mL Streptococcus feed (Sigma Aldrich) and medium (DMEM; Invitrogen) supplemented with it puts the hemp cloth nose was cultured in modified eagle maintaining. The 6 - well plate (well plat) proliferation of analyzing using L-a 929, MTT was determined by screen analysis. First, 1 × 10 per well5 6 - well plate to which is included in the culture of cells after 48 hours (well plat), or said elution 50%, 25%, 12. 5%, 6. 3%, 3. 1%, 1. 5% dilution to a few cell processing, him as 24 hours. Then, MTT analysis stored in the dose through the phosphoric acid buffer solution and washing. Said evaluation result, nano - HA fixed bone support surface of the present invention L-a 929 cell survival rates does not influence any cell proliferation into foods. As a result nano - HA fixed bone support surface 24 hours L-a 929 cells cells-processes, exhibits no meal wisdom tooth no longer influence. 2 - 5 animal bone graft evaluation Fixed to the support surface in said in the embodiment 3 number nano - HA high pressure liquid coolant was assessed test animal bone graft material. Controls include "biological safety of medical device a common reference standard" number in the deflection timing polyethylene (polyethylene), 2 mm diameter and 6 mm in length after a water test sample compared with a command of the troop polyethylene work grudge number, his EO gas sterilization. First, rabbit anesthetic supply and, during test pulse of rabbit heart rate by checking, the state of health of rabbit therefrom. The tibia [...] rabbit brain implantation site and, after beta DIN disinfected, exposing the brain tibial cortical portion, drill can also be inserted into a suitable hole by a bone support his feet. Bone support of the present invention parallel opposite from the regulated after implantation, cortex department exposed tibial component covering the first sealed rabbit been stabilized. Then, have main 12 during implantation, tester during rabbit to view, and it is confirmed whether topical or systemic no side effect. After testing, the canvass rabbit and tested for exposing a region to necrosis or surrounding tissue varying observed with the human eye. Then, the state surrounding tissue, after collecting the implantation site, 10% formalin solution and conducting dyeing H&E pathological tissue. Said evaluation result, nano - HA fixed bone support surface when implantation of the present invention, implantation of the troop polyethylene contrast not to induce, 1 bone regeneration. 5 times activated as in the picomolar. These results indicate that the FP-a 151 RGD recombinant adhesive protein within the bone support of the present invention based on bone binder as well as helping to launching the bone reproducing bone graft bar can be know. The present invention relates to a bone binder for preventing or treating a periodontal disease by using a dopa-Fe-(III) composite on the basis of a mussel adhesive protein having a drug loaded therein, and to a method for producing the same. The bone binder according to the present invention is produced by using a catechol compound-metal coordinate complex, specifically, a dopa-Fe(III) composite on the basis of a mussel adhesive protein. Accordingly, biocompatibility is excellent, and a discharge speed of a loaded drug can be controlled. Also, a strong bone adhesive force is ensured. Thus, the bone binder is effective in preventing or treating a periodontal disease, and can be useful in performing an implant operation for a patient having defective bony tissue. COPYRIGHT KIPO 2016 Recombinant adhesive protein and a drug including, for prevention or treatment of periodontal disease bone binder. According to Claim 1, characterized in that said recombinant adhesive protein is tyrosine residues converted into a catechol compounds, for prevention or treatment of periodontal disease bone binder.
According to Claim 2, said catechol compounds are waveguide (3,4 non-dihydroxyphenylalanine, DOPA), waveguide quinone (Dopa-O-quinone), toe group (2, 4, 5 provided trihydroxyphenylalanine, TOPA), toe group quinone (Topa quinone) and their derivatives selected from the group consisting of not more than 1 species characterized, for the prevention or treatment of periodontal disease bone binder. According to Claim 2, said catechol compounds are organic metal to form a metal coordination complex - characterized by catechol compounds, for prevention or treatment of periodontal disease bone binder. According to Claim 4, catechol compounds (DOPA)- Fe (III)- said metal coordination complex is characterized in that the refractive index of the composite, for the prevention or treatment of periodontal disease bone binder. According to Claim 4, said metal is iron (iron), titanium (titanium), vanadium (vanadium), chromium (chrome), manganese (manganese), cobalt (cobalt), Ni (nickel), zirconium (zirconium), niobium (niobium), Mo (molybdenum), technetium (technetium), ruthenium (ruthenium), Rh (rhodium), palladium (palladium), is (silver), hafnium (hafnium), tantalum (tantalum), tungsten (tungsten), rhenium (rhenium), osmium (osmium), iridium (iridium), and gold (gold) platinum (platium) selected from the group consisting of not more than 1 species characterized, for prevention or treatment of periodontal disease bone binder. According to Claim 1, said recombinant adhesive protein is the sequence numbers 1, sequence number 2, the sequence numbers 3, sequence number 4, the sequence numbers 5, sequence number 6, sequence number 7, the sequence numbers 8, 9 sequence number, sequence number 10, the sequence numbers 11, 12 sequence number, sequence number 13, sequence number 14, the sequence numbers 15, 16 17 and sequencing of at least one selected from the group consisting of sequence number 1 number consisting of the amino acid sequences of characterized, for the prevention or treatment of periodontal disease bone binder. According to Claim 1, said recombinant adhesive protein is luck thread end (carboxyl-a-terminal) or amino end group content of said recombinant adhesive protein carboxylic acids including 3 to 25 amino acids (product-a-terminal) is connected to a of RGD polypeptides characterized, for prevention or treatment of periodontal disease bone binder. According to Claim 1, characterized in that said antibacterial number number or anti-inflammatory drug, binder headphone for prevention or treatment of periodontal disease. According to Claim 9, number said antimicrobial is chlorhexidine, [...] process, diamino cyclin, tetracycline, as antiprotozoal [...], of vancomycin, [...], phosphor feed, [...], pro [...], cancerous blood thread phosphorus, penicillin-resistant Streptococcus pneumoniae, killing by poisoncycle phosphorus, as antiprotozoal it will be born in the mote, cephalosporin, nor car D new, gentamicin, erythromycin neohesperidin dihydrochalcone, republic of Ghana feed, yeast, roh Eamerican crow lysine, amino car new, assimilable lama capsaicin, d hemp cloth car new, [...] cells, into cephalosporin, erythromycin, [...] cycle, memory where, to the jade it lived, is not less than 1 species selected from the group consisting methicillin-and backsightdick it buys width characterized, for prevention or treatment of periodontal disease bone binder. According to Claim 1, characterized gingivitis or periodontal disease can said to be oral, binder headphone for prevention or treatment of periodontal disease. According to Claim 1, said bone binder shutter apparatus bone, upper jaw, mandible angle, evil joint, adhering to an alveolar bone or a pin portion characterized, for prevention or treatment of periodontal disease bone binder. According to Claim 1, 1 to 50% by weight based on the total weight of recombinant adhesive protein said bone binder including a contrast characterized, for prevention or treatment of periodontal disease bone binder. According to Claim 1, characterized in that said drug release number plower the bone binder, binder headphone for prevention or treatment of periodontal disease. According to Claim 1, said bone binder gel, hydrogel, fiber, powder, cream, pack, sheet and oil consisting of at least one number selected from the group consisting 1 a type characterized, for prevention or treatment of periodontal disease bone binder. (1) recombinant adhesive protein, drug and containing xanthan gum having per dissolving solvent mixture; and (2) heating said 30 provided 50 °C mix solution in 20 - 30 hours; including a, gel number for prevention or treatment of periodontal disease of bone binder manufacturing method. According to Claim 16, said (1) step, recombinant adhesive protein 0. 1 - 10% by weight, drug 0. 1 - 10% by weight and a thickening 0. 1 - 10% by weight the including a characterized, bone binder manufacturing method for prevention or treatment of periodontal disease. (1 ') recombinant adhesive protein, drug, vinylpyrrolidone (vinyl prrrolidone) and meta [...] (methacrylate) dissolving a mixture of solvent; (2') AIBN (azobisisobutyronitrile) without further application in said mixed solution and then polymerizing and cross-number 40 provided 80 °C, washed methanol; and (3') in 2 - 4 days drying said cleaning polymer 30 provided 50 °C; including a, hydrogel number for prevention or treatment of periodontal disease of bone binder manufacturing method. According to Claim 18, said (2') in, number (ethyleneglycol dimethacrylate) is crosslinked EGDMA, photoresist mote, hydroxyphenyl acetic acid, hydroxy propionic acid, dopamine, epitaxial hydroxy species selected from the group consisting of not more than 1 general it is hour ethyl aniline characterized, bone binder manufacturing method for prevention or treatment of periodontal disease. (1 ") recombinant adhesive protein, drug, poly gamma glutamic acid (polygammaglutamic acid, a Γ-pGA) hyaluronic acid and dissolving solvent mixture; and (2") said electrospun mix solution step; including a, manufacturing method for prevention or treatment of periodontal disease of bone binder number electrospun fibers. According to Claim 20, said (2") in, electric radiation voltage 8 provided 25kV, radiation distance of 5 a-20cm and syringe pump fluid velocity 0. 2 a-5ml/h condition characterized by being performed in a non-, bone binder manufacturing method for prevention or treatment of periodontal disease. Number 16 anti, anti either as described in claim number 18 term and a number 20, said solvent is distilled water, process [...] (hexafluoroisopropanol), styrene thermoplastic rubber (trifluoroacetic acid), dimethylformamide amide (dimethyl formamide), dimethyl sulfoxide (dimethyl sulfoxide), TFE (trifluoro ethylene), acetone (acetone), MC (methylene chloride), THF (tetra hydro furan), acetic acid (acetic acid) and formic (formic acid) selected from the group consisting of not more than 1 species is characterized, bone binder manufacturing method for prevention or treatment of periodontal disease. According to Claim 1 including the binder which it boils, bone support. According to Claim 23, said bioactive materials including a bone support characterized, bone support. According to Claim 24, said bioactive materials nano hydroxyapatite, gold nanoparticles, peptide, enzyme, transcription factor, small molecule drug, liposome, nucleotide, toxin, antigenic peptides, antibody, hormone, carrier protein, immunoglobulin, structural protein, a motor function protein, receptor, signal (signaling) protein, a seed storage protein, membrane protein, protein trans-membrane (transmembrane), internal (internal) protein, external (external) protein, secreted protein, viral protein, congenital (native) protein, per protein, cutting protein, protein having disulfide bonds, protein complex, chemically modified protein, prion (prions), and antibody fragment selected from the group consisting of not more than 1 species characterized, bone support. According to Claim 1 according to Claim 23 including bone binder or bone support, implant kit. As Cd Pb Hg Measurements (ppm) N. D N. D N. D N. D MDL 0. 5 0. 5 5. 0 1. 0 Porosity (%) Compressive strength (Mpa) 88. 7 ± 0. 50 1. 81 ± 0. 78 78. 2 ± 0. 54 20. 5 ± 4. 21 74. 17 ± 0. 43 25. 03 ± 1. 52 71. 62 ± 0. 82 28. 4 ± 2. 14 68. 11 ± 0. 25 33. 4 ± 5. 29
