WO2016006889A1 - Surface-coated dental implant with improved bioaffinity and biocompatibility and method for manufacturing same - Google Patents

Abstract

The present invention relates to a dental implant and a method for manufacturing the same, wherein the dental implant has improved bioaffinity such as hydrophilicity, hemocompatibility, bone formation promotion capability and bone-interface binding force by coating the surface of the dental implant using a composition for coating implants and, more specifically, to a dental implant having improved bioaffinity or biocompatibility by coating the pre-processed surface of the implant using a composition for coating implants, and a method for manufacturing the same. The dental implant coated with a composition for coating implants, according to the present invention, has advantages that hydrophilicity, hemocompatibility and bone-interface binding force are improved and the formation of bone around an implanted implant is enhanced, and also has effects of improving bioaffinity and biocompatibility of the dental implant.

Description

Surface-coated dental implants with improved biocompatibility and biocompatibility and methods for their preparation

The present invention relates to a dental implant and a method for manufacturing the same by improving the biocompatibility of the implant by coating the surface of the implant using the composition for implant coating, such as hydrophilicity, blood affinity, bone formation promoting ability and bone interface binding strength of the implant, More particularly, the present invention relates to a dental implant and a method for producing the same, which are coated with a pre-treated implant surface using an implant coating composition, thereby improving biocompatibility or biocompatibility.

As the aging society progresses, quality of life is emerging as a social issue, and attention to health is being subdivided. In particular, oral health has a direct impact on general health, but tooth loss due to aging is inevitable. .

Proper teeth treatment such as dentures and bridges is the main solution to tooth loss because it does not affect food intake and affects interpersonal relationships due to digestive problems, facial deformation and incorrect pronunciation. In recent years, implant surgery, a treatment approach that is close to natural teeth, has emerged, and implant surgery has been recognized as a universal treatment method for tooth loss due to the improvement of consumer's income level and the development of dental dental technology.

Dental implants are used to permanently implant artificial teeth on the jaw bone of humans. The dental implant connects the jaw bone with artificial teeth and handles and distributes the load generated when chewing food. It is mechanically manufactured to serve as a more stable tooth than a conventional denture. Therefore, the implant should be made of biocompatible materials that are very stable against human tissues and should be free of side effects and other chemical and biochemical reactivity. In addition, it is very difficult to select a suitable material because the mechanical strength must be very high so as not to be deformed and destroyed even under repeated loads and instantaneous pressures.

Various metals and alloys have been developed and tried as suitable materials for implants, but titanium (Ti) metals and alloys are mainly used (Larry L. Hench, "Bioceramics", J. Am. Ceram. Soc. 81 (7) 1705 -1728, 1998). Titanium or its alloys are not only easy to process but also have the advantages of high biocompatibility, high mechanical strength and bioinertness to human tissues. However, Ti and its alloys have a disadvantage in that the bonding time with the bone is long when transplanted into the human body, and metal ions melt into the living body after a long time after transplantation.

In order to make up for these drawbacks, techniques that can enhance bone bonding by appropriately treating the surfaces of these materials have been developed and used (Korean Patent Publication No. 2013-0022252). In particular, the surface treatment method of the implant has been pointed out as an important determinant in osseointegration. In this connection, the smooth surface treatment method by lathe processing has the longest history due to its excellent biocompatibility and tissue stability. Has been applied to implant procedures.

However, efforts have been made to improve the surface characteristics of implants to improve the success rate in bones with low bone density. Implants with irregular surfaces are effective for rapid bone growth and good mechanical adhesion, and implants with irregular and rough surfaces. Has been reported to have more bone contact rates than implants with smooth surfaces.

Looking at the evolution of the implant surface, the first-generation implant is an implant with a smooth surface, and the second-generation implant is an implant with an anodized surface. , TPS). Implants with a Resorbable Blasted Media blasting (RBM) surface belong to the third generation of implants and have increased the roughness of the implant using blasting techniques as an absorbent medium. This blasting method has the advantage that the surface area is increased by the effect of particles sprayed on the surface to increase the implant interfacial bone bonding force due to the uneven effect and to activate the reaction of the cells on the rough surface.

However, in the case of a surface treatment method such as the RBM, which is a widely used implant surface treatment method, and a high biocompatibility SLA (Sandblast Large grit Acid etch) surface treated with an acidic substance, the product is exposed to air after the surface treatment process. In this case, the oxide layer grows on the surface of the product, and adsorption of various pollutants such as hydrocarbons occurs, resulting in hydrophobization while changing to a chemically stable state. That is, the hydrophobized surface has a disadvantage of prolonging the period of stabilization of the implant by preventing the overall process of fusion with the bone after implant implantation because of low wettability to body fluids and blood.

On the other hand, US Patent 6670855 discloses a method of chemically etching with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, etc. as a method of improving the hydrophilicity of the roughened surface of the titanium implant, Plasma treatment (Radio-Frequency Glow Discharge (RFGD), O2, etc.), light irradiation (ultraviolet radiation, ultraviolet-ozone) as a method of imparting hydrophilicity of the metal surface to overcome the disadvantages of hydrophobicity of titanium surface Etc.).

However, if applied, it is possible to superhydrophilize the titanium surface, but there are still limitations in terms of improving the quality such as the rate of bone bonding, maintaining hydrophilicity for a certain period of time.

Accordingly, the present invention provides a composition for implant surface coating that can be coated on the surface of the implant, thereby improving the hydrophilicity, blood affinity, bone formation promoting ability, etc. of the implant surface, by using the same, improved biocompatibility and biocompatibility The present invention proposes a method for preparing a dental implant and a dental implant manufactured by the method.

Therefore, an object of the present invention is a method of coating an implant surface using a composition for implant surface coating comprising a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 3] or a salt thereof as an active ingredient And the implant surface coating composition is coated to provide a dental implant with improved biocompatibility and biocompatibility.

[Formula 1]

In Formula 1, R1 is -PO (OH) ₂ or -SO ₂ (OH), R2 is hydrogen or -OH, R3 is hydrogen or -NH ₂ , R4 is oxygen or -NH ₂ .

[Formula 2]

In Formula 2, a ₁ and a ₂ are each independently —PO (OH) ₂ or —SO ₂ (OH), and Q ₁ and Q ₂ are each independently hydrogen or —NH ₂ .

[Formula 3]

In [Formula 3] a is -PO (OH) ₂ or -SO ₂ (OH).

Another object of the present invention is to provide a method for treating a surface of an implant comprising: (a) pretreatment to roughen the surface of the implant; And (b) roughening the implant coating composition comprising a compound selected from the group consisting of compounds represented by the above [Formula 1] to [Formula 3] or salts thereof as an active ingredient in the pretreatment step (a). By coating the implant surface, it is to provide a dental implant manufacturing method with improved biocompatibility or biocompatibility, such as hydrophilicity, blood affinity, bone formation promoting ability and bone interface binding strength of the implant.

The dental implant with improved biocompatibility presented in the present invention comprises a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 3] or salts thereof as an active ingredient, on the surface of the dental implant The concentration of the composition to be coated is 0.05 to 0.5 M, pH is characterized in that 5 to 9.

[Formula 1]

In Formula 1, R1 is -PO (OH) ₂ or -SO ₂ (OH), R2 is hydrogen or -OH, R3 is hydrogen or -NH ₂ , R4 is oxygen or -NH ₂ .

 [Formula 2]

In Formula 2, a ₁ and a ₂ are each independently —PO (OH) ₂ or —SO ₂ (OH), and Q ₁ and Q ₂ are each independently hydrogen or —NH ₂ .

[Formula 3]

In [Formula 3] a is -PO (OH) ₂ or -SO ₂ (OH).

The compound selected from the group consisting of the compound represented by the above [Formula 1] to [Formula 3] or a salt thereof is coated on the surface of the implant is preferably coated on the dental implant surface in an amount of 10 ~ 40 ㎍ / ㎜. .

More specifically, the compound of [Formula 1] is preferably 2'-deoxyadenosine 5'-monophosphate (hereinafter referred to as 'DAP') or 2'-deoxycytidine 5'-monophosphate (hereinafter referred to as 'DCP'). In addition, the compound of [Formula 2] is preferably 4,4'-Diaminostibene-2,2'-disulfonic acid (hereinafter referred to as 'DASDA').

In the case of the compound represented by [Formula 3] or a salt thereof, it is preferable to coat the surface of the dental implant in an amount of 1 μg / mm 2 ~ 1 mg / mm 2, wherein the compound of Formula 3 is N-Tris (hydroxymethyl) It is preferably methyl-3-aminopropanesulfonic acid (hereinafter referred to as 'TAPS').

Therefore, the dental implant coating composition used in the present invention includes DAP, DCP, DASDA, TAPS or salts thereof as an active ingredient, pH is 5 ~ 9, more preferably 0.05 ~ 0.5 in the range of pH 6 ~ 8 It is included in the concentration of M.

When coated on the dental implant surface, the composition containing DAP, DCP, DASDA or salts thereof is coated in an amount of 10-40 μg / mm 2 per unit area, and the composition containing TAPS or salt thereof is 1 μg per unit area. / Mm2-1 mg / mm2.

Another embodiment of the present invention is a method for manufacturing a dental implant, (a) pre-treatment step of roughening the surface of the dental implant through the blasting and acid treatment step; And (b) a composition comprising a compound selected from the group consisting of the compounds represented by the above [Formula 1] to [Formula 3] or a salt thereof as an active ingredient, the coating on the implant surface subjected to the pretreatment step (a) It includes; step.

Dental implants coated with the composition for implant coating presented in the present invention has the advantage that the surface hydrophilicity, blood affinity and bone-interface force is improved, the bone formation of the peripheral portion implanted is greatly increased, dental implants The biocompatibility or biocompatibility of the is greatly improved.

Figure 1 shows the results of the contact angle test of the coated dental implant.

Figure 2 shows the results of blood affinity measurement experiment of the coated dental implant of the present invention.

Figure 3 shows the experimental results of measuring the bone interface binding force of the coated dental implant of the present invention.

Figure 4 is a μ-CT imaging results for bone interface morphometric evaluation of the coated dental implant of the present invention.

The compounds represented by [Formula 1] to [Formula 3] of the present invention may be used in the form of a salt thereof, or a pharmaceutically acceptable salt thereof. As used herein, 'pharmaceutically acceptable' refers to a physiologically acceptable and normally does not cause an allergic or similar reaction when administered to a human, and as the salt, a pharmaceutically acceptable free acid Acid addition salts formed by

[Formula 1]

In Formula 1, R1 is -PO (OH) ₂ or -SO ₂ (OH), R2 is hydrogen or -OH, R3 is hydrogen or -NH ₂ , R4 is oxygen or -NH ₂ .

 [Formula 2]

In Formula 2, a ₁ and a ₂ are each independently —PO (OH) ₂ or —SO ₂ (OH), and Q ₁ and Q ₂ are each independently hydrogen or —NH ₂ .

[Formula 3]

In [Formula 3] a is -PO (OH) ₂ or -SO ₂ (OH).

As the free acid used in the present invention, an organic acid or an inorganic acid may be used, and as the organic acid, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, meta Sulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, glutamic acid, aspartic acid, and the like, but are not particularly limited thereto. In addition, the inorganic acid includes hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, and the like, but is not limited thereto.

Experiment using various coating compositions to determine whether the compound selected from the group consisting of a compound represented by the above [Formula 1] to [Formula 3] or salts thereof is suitable for use as a material for dental implant coating TMP (Thiamine monophosphate), FA (Folic acid), MDP (Methylene diphosphonic acid) and the like were used for the comparison.

When the surface of the disk of the implant specimen is coated using a compound selected from the group consisting of a compound represented by [Formula 1] to [Formula 3] or a salt thereof of the present invention, accelerated aging conditions of 3 years (55 ℃ After 18 weeks of standing), the contact angle was very low compared to the case where other comparative materials were coated, which means that the coated compound greatly increased the hydrophilicity of the implant surface (see FIG. 1 described later).

In addition, as a result of measuring blood affinity with an implant specimen in the form of a fixture, an implant coated with a compound selected from the group consisting of compounds represented by [Formula 1] to [Formula 3] or salts thereof of the present invention The accelerated aging condition showed very high blood affinity compared with the case of coating with other comparative materials (see FIG. 2 below), and the measurement of the interfacial force in vivo with a fixture type implant specimen Again showed better bone-interface force compared to the case of using the comparative material (see FIG. 3 described later).

The composition for implant coating of the present invention may be molded and used in the form of putty, paste, moldable strip, block, chip, etc. using a method of compression, compression, pressure contact, packing, pressing, hardening, and the like, and chemical additives. It may be used in the form of gels, powders, pastes, tablets, pellets, etc., but is preferably used in the form of an aqueous solution.

When used in the form of an aqueous solution, the concentration of the coating composition to be coated on the implant surface is 0.05 ~ 0.5 M, the pH is preferably 5 ~ 9, more preferably 6 ~ 8, the surface of the implant [Formula 1] Alternatively, the compound represented by [Formula 2] is preferably coated in an amount of 10 to 40 μg / mm 2, and the compound represented by [Formula 3] is preferably coated in an amount of 1 μg to 1 mg / mm 2.

In this case, when the concentration is less than 0.05 M, the amount of the coating on the implant surface may be too small to improve the biocompatibility, and when the concentration is 0.5 M or more, it is difficult to uniformly coat the entire surface due to the high viscosity. The thick coating layer causes problems such as long-term dropout stability due to vibration and dropping.

In addition, in the case of the coating composition in the form of the aqueous solution, the pH is preferably in the range of about 5 to 9, which is a neutral region including weakly acidic to weakly basic regions. When the pH is less than 5, the surface of the implant base may be oxidized. There is a problem that can be, if the pH is more than 9 is not preferable because the problem of lowering the material stability of the coating composition itself.

As a specific form of the compound of [Formula 1], 2'-deoxyadenosine 5'-monophosphate (hereinafter referred to as' DAP ') or 2'-deoxycytidine 5' represented by the following [Formula 4] or [Formula 5] -monophosphate (hereinafter referred to as 'DCP'), including salts thereof.

[Formula 4]

2'-deoxyadenosine 5'-monophosphate (DAP)

[Formula 5]

2'-deoxycytidine 5'-monophosphate (DCP)

In addition, as a specific form of the compound of [Formula 2], 4,4'-Diaminostibene-2,2'-disulfonic acid (DASDA) represented by the following [Formula 6] can be included, and salts thereof do.

[Formula 6]

4,4'-Diaminostibene-2,2'-disulfonic acid (DASDA)

And Specific examples of the compound of [Formula 3] include N-Tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid (TAPS) represented by the following [Formula 7], the salt thereof is included.

[Formula 7]

N-Tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid (TAPS)

Therefore, the dental implant coating composition used in the present invention includes DAP, DCP, DASDA, TAPS or a salt thereof as an active ingredient, pH is contained in a concentration of 0.05 to 0.5 M in the range of 5-9.

When coated on the dental implant surface, the composition comprising DAP, DCP, DASDA or salts thereof is preferably coated in an amount of 10-40 μg / mm 2 per unit area of the implant. In addition, a composition containing TAPS or a salt thereof may be used per 1 implant unit area. It is preferable to coat in an amount of µg / mm 2 to 1 mg / mm 2.

At this time, if the amount of coating is less than the above range there is a problem that can not cover the entire surface of the implant, if the coating amount exceeding the above range because a thick coating layer is formed, problems such as dropping due to vibration during distribution As it may, it is not preferable.

In addition, when used for coating the surface of the implant in the form of such an aqueous solution, an additional biologically active substance may be added and used, growth factors for promoting bone growth, peptides and proteins for promoting bone tissue formation, Fibrin, bone morphogenic factors, bone growth agents, chemotherapeutic agents, antibiotics, analgesics, bisphosphonates, strontum salts, fluoride salts, magnesium salts, sodium salts and the like can be used.

The growth factors include bone morphogenic protein (BMP), platelet-derived growth factor (PDGF), transgenic growth factor (TGFbeta), insulin-like growth factor (IGF-I), IGF-II, fibroblast growth factor (FGF) and BGDF-II (beta-2-microglobulin), and the like, and the bone tissue formation-promoting peptides and proteins include various peptides including RGD sequences and various proteins such as collagen and fibronogen.

Osteocalcin, bonesialo protein, osteogenin, BMP, and the like may be used as bone morphogenesis factors, and the bone growth agent may be harmful if it is harmless to the human body and promotes bone growth. It can be used without, nucleic acids that promote bone formation, antagonists of substances that inhibit bone formation, and the like.

In another embodiment of the present invention (a) a pretreatment step of roughening the surface of the implant; And (b) coating the implant coating composition of the present invention on the surface of the implant pretreated in step (a).

The step (a) is a step of pretreating the surface of the implant before coating with the composition for implant coating of the present invention, various pretreatment methods known in the art can be used. For example, RBM (Resorbable Blasting Media) method using surface-absorbing spray particles, SA (Sand-blasted Large grit, and Acid etched) surface treatment method after etching with aluminum after aluminum blasting, UV irradiation, temperature above 300 ℃ Heat treatment, or anodizing, acid treatment, and heat treatment after base treatment, and the like, preferably UV irradiation or SA (Sand-blasted Large grit and Acid etched) surface treatment, and the like. Consider a pretreatment step that performs both.

In addition, the material of the implant used in the present invention is not particularly limited, and all known implant materials are possible, and ceramics such as Glass, ITO, synthetic polymers such as PU, PTFE, and metals may be used as SiO ₂ , Pt, St, Titanium, a titanium alloy, etc. are mentioned. Preferably, titanium or titanium alloy may be used, and in the aforementioned pretreatment (surface treatment) step, nitric acid solution may be used to remove carbon hydroxide on the surface of the titanium or titanium alloy implant.

The nitric acid solution is preferably about 4 v / v% to 60 v / v%, and the nitric acid solution cleaning process may be omitted depending on the hydrophilic property and shape of the surface. After nitric acid washing, it is preferable to wash the surface with distilled water to remove residual nitric acid from the surface, and the surface washing process of distilled water may be omitted on the surface where the nitric acid solution cleaning process is omitted, but following the alcohol washing step to remove impurities Can be used.

Step (b) is a step of coating the surface of the implant using the composition for implant coating of the present invention, specific implant surface coating method may include a physical and chemical coating method. Specific examples include pulsed laser deposition (PLD), sputtering, sputtering, chemical vapor deposition (CVD), dip coating, spin coating, plating, and three-dimensional plasma dry deposition ( 3D plasma gun deposition). In addition to the coating method, the coating composition of the present invention may be dried by a simple application process on the surface of the implant, thereby performing a coating step. At this time, the room temperature drying time may be about 1 to 24 hours, more preferably 1 to 3 hours.

In general, UV irradiation process or SA treatment process is known to induce bone adhesion, but there is a disadvantage that the biocompatibility falls after a certain time after treatment. However, the surface-coated implant using the coating composition of the present invention has the advantage of maintaining or enhancing the biocompatibility of the implant even after a long time.

Hereinafter, with reference to the embodiments and the drawings in order to look at the technical features of the present invention in detail. However, the technical spirit of the present invention is not limited through these specific embodiments, and the technical spirit of the present invention should be protected with respect to the claims and their equivalents.

Example 1

Formation of dry coating layer of the composition for pretreatment and coating of dental implant surface

Specimens used were made of titanium (CP Ti Gr4, Siwon company, USA) in a precision CNC dedicated to implants (CINCOM.L20VIII, Japan) with a diameter of 10 mm, a thickness of 1 mm and a screw shape of 1.5 mm and a length of 1.5 mm. After processing in the form of a fixture, using an Al ₂ O ₃ powder having a particle size of 50 μm and blasting for 30 seconds at a blast pressure of 5 atm, macro-morphology was applied to the surface of the implant using an acid treatment method using a mixed acid aqueous solution. And micro-morphology.

After the pretreatment, the implant was washed. The acid-treated dental titanium implant was ultrasonically cleaned for 30 minutes with ethanol and for 30 minutes with distilled water and then dried.

The treated implant was treated with plasma for 1 minute or ultraviolet light for 5 minutes to remove contaminants adsorbed and stabilized on the surface, and pH 0.1 M TMP, FA, MDP, DAP, DCP, DASDA and TAPS aqueous solutions were applied to the surface. After adjusting to 7, uniformly uniformly applied, and dried at room temperature to prepare a 25 μg / mm 2 (0.5 mg / mm 2 in the case of TAPS) coating amount. TMP, FA, MDP, DAP, DCP, DASDA and TAPS aqueous solution prepared by this method was coated in the following [Example 2].

Example 2

Contact angle measurement for checking hydrophilicity of coated implants

The Sessile drop method was used to measure the hydrophilicity of the coated implant surface prepared in [Example 1].

Prior to the contact angle measurement, the TMP, FA, MDP, DAP, DCP, DASDA and TAPS coated titanium disks prepared in [Example 1] were left for 18 weeks (accelerated aging 3 years) under accelerated aging conditions (55 ° C). After that, 10 ml of distilled water was dropped into each of the accelerated aging disks, respectively, and the contact angle between the surface and distilled water was measured. In order to accurately measure the contact angle, a picture was taken with a video camera-equipped device (Contact angle measurement, Surface Tech, Korea), and the left and right contact values were measured, and then an average value (Contact angle) was obtained.

At this time, the SA disk immediately after the manufacture of the surface coating is not made as a positive control, the SA disk accelerated aging in a state in which the surface coating is not made as a negative control.

As can be seen from the experimental results of FIG. 1, the contact angle of distilled water in TMP, FA, MDP, DAP, DCP, DASDA and TAPS coated experimental groups compared to the negative control group having a contact angle of 121 ° for 18 weeks (accelerated aging) 3 years. It can be seen that the contact angle is lowered to about 0 °, 12 °, 60 °, 0 °, 0 °, 0 °, and 0 °, respectively, thereby improving the hydrophilicity of the coating surface.

Example 3

Blood Wetting of Surface-Coated Implants

The dental implant coated with the surface prepared in Example 1 was left for 18 weeks under accelerated aging conditions (55 ° C.), and then the implant was immersed in micropig blood for about 3 mm for 3 minutes to check blood affinity. After that, the blood wettability was confirmed by the height of the blood coming up the surface of the implant.

In this case, the SA control which was not coated with the materials immediately after the preparation was used as the positive control, and the SA implant that was subjected to accelerated aging conditions without coating the material as the negative control was used.

As confirmed in the experimental results of Figure 2, accelerated aging TMP, FA, MDP, DAP, DCP, DASDA and TAPS coated dental implants were confirmed that the blood wettability is higher than the negative control SA implants. The negative control SA implant had 1.5 mm of blood coming up the surface of the implant for 3 minutes, whereas 6 mm, 4 mm, and 3 mm for TMP, FA, MDP, DAP, DCP, DASDA and TAPS, respectively. , 8.5 mm, 8 mm, 8.3 mm and 8.5 mm was found to significantly improve the blood wettability.

Through the measurement of blood wettability, it can be seen that blood affinity of the surface coated implant surface is improved even under conditions of 3 years of accelerated aging.In particular, the surface coated implants with DAP, DCP, DASDA and TAPS are compared to the negative control group. It can be seen that the affinity is greatly improved.

[ Example  4]

Measurement of Bone-Interface Cohesion of Surface-Coated Implants (In vivo )

TMP, FA, MDP, TMP, FA, MDP, DAP, DAP, DCP, DASDA and TAPS prepared in [Example 1] were confirmed to have excellent blood affinity through [Example 3] dental implants. DAP, DCP, DASDA, and TAPS coated implants were left for 18 weeks (accelerated aging) for 18 weeks under accelerated aging conditions (55 ° C), and the implant and bone-interface binding force were confirmed.

The surface-coated implant was placed in the tibia of the rabbit to measure the implant and bone-interfacial binding force, and the torque was measured after 14 days of bone formation.

As a positive control, the surface-free SA implant immediately after preparation was used, and as a negative control, an accelerated aging SA implant was used for the same period without the surface being coated.

As can be seen from the results of FIG. 3, in the case of an implant experimental group coated with TMP, FA, MDP, DAP, DCP, DASDA, and TAPS compared to the negative control even after accelerated aging for 18 weeks (accelerated aging 3 years), It can be seen that the torsional removal force is about 131%, 110%, 114%, 148%, 150%, 150%, 148%, respectively, and the bone-interface binding force is improved. In particular, in the case of DAP, DCP, DASDA, and TAPS surface-coated implants, the bone interface binding force of SA immediately after preparation, which is a positive control, was almost equivalent to or slightly improved.

Example 5

Measurement of Bone Interface Morphology of Surface-Coated Dental Implants

TMP, DAP, DCP, DASDA and TAPS coated with high torsional removal of [Example 4] among the dental implants coated in TMP, FA, MDP, DAP, DCP, DASDA and TAPS prepared in [Example 1] Implants were selected and left for 18 weeks (accelerated aging 3 years) under accelerated aging conditions (55 ° C), followed by morphometric evaluation of the bone interface.

For morphometric evaluation of bone-interface, implantation of TMP, DAP, DCP, DASDA and TAPS surface-coated implants into micro pig mandible was performed and then morphometric measurement by μCT imaging after 16 days of bone formation period. Physiological evaluation was performed.

As a positive control, a surface-free SA implant immediately after preparation was used. As a negative control, an SA-implant accelerated for the same period without coating the surface coating composition was used.

As can be seen from the results of FIG. 4, despite 18 weeks of accelerated aging, the dental implants coated with DAP, DCP, DASDA and TAPS have a significantly increased degree of bone formation around the implant compared to the negative control. You can see that.

Dental implants coated with the composition for implant coating presented in the present invention is improved hydrophilicity, blood affinity and bone-interface force of the surface, increased bone formation in the periphery in which the implant is placed, bio-compatibility of the dental implant Alternatively, since there is an effect of greatly improving biocompatibility, there is industrial applicability.

Claims (10)

1. A dental implant coated with a coating composition comprising a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 3] or salts thereof as an active ingredient.

   [Formula 1]

   

   In Formula 1, R1 is -PO (OH) ₂ or -SO ₂ (OH), R2 is hydrogen or -OH, R3 is hydrogen or -NH ₂ , R4 is oxygen or -NH ₂ .

    [Formula 2]

   

   In Formula 2, a ₁ and a ₂ are each independently -PO (OH) ₂ or -SO ₂ (OH), and Q1 and Q2 are each independently hydrogen or -NH ₂ .

   [Formula 3]

   

   In [Formula 3] a is -PO (OH) ₂ or -SO ₂ (OH).
2. The method of claim 1,

   The concentration of the coating composition is 0.05 ~ 0.5 M, pH is characterized in that 5 to 9, dental implants.
3. The method of claim 1,

   The compound represented by the above [Formula 1] or [Formula 2] or a salt thereof is characterized in that the dental implant is coated on the surface of the dental implant in an amount of 10 to 40 ㎍ / ㎜.
4. The method of claim 1,

   The compound represented by the above [Formula 3] or a salt thereof is a dental implant, characterized in that the coating on the surface of the dental implant in the amount of 1 μg / mm 2 ~ 1 mg / mm 2.
5. The method of claim 1,

   The coating composition, 2'-deoxyadenosine 5'-monophosphate (DAP), 2'-deoxycytidine 5'-monophosphate (DCP), 4,4'-Diaminostibene-2,2'-disulfonic acid (DASDA), N-Tris A dental implant comprising (hydroxymethyl) methyl-3-aminopropanesulfonic acid (TAPS) or a salt thereof.
6. (a) pretreatment step of roughening the surface of the dental implant through the blasting and acid treatment step; And

   (b) a coating composition comprising a compound selected from the group consisting of compounds represented by the following [Formula 1] to [Formula 3] or a salt thereof as an active ingredient, on the surface of the implant pretreated in the pretreatment step (a) A method of manufacturing a dental implant comprising; coating.

   [Formula 1]

   

   In Formula 1, R1 is -PO (OH) ₂ or -SO ₂ (OH), R2 is hydrogen or -OH, R3 is hydrogen or -NH ₂ , R4 is oxygen or -NH ₂ .

    [Formula 2]

   

   In Formula 2, a ₁ and a ₂ are each independently —PO (OH) ₂ or —SO ₂ (OH), and Q ₁ and Q ₂ are each independently hydrogen or —NH ₂ .

   [Formula 3]

   

   In [Formula 3] a is -PO (OH) ₂ or -SO ₂ (OH).
7. The method of claim 6,

   The concentration of the coating composition is 0.05 ~ 0.5 M, pH is 5 ~ 9, characterized in that the dental implant manufacturing method.
8. The method of claim 6,

   The compound represented by the above [Formula 1] or [Formula 2] or a salt thereof is coated on the surface of the dental implant in the amount of 10 to 40 ㎍ / ㎜, method for producing a dental implant.
9. The method of claim 6,

   The compound represented by the above [Formula 3] or a salt thereof is coated on the surface of the dental implant in the amount of 1 μg / mm 2 ~ 1 mg / mm 2, a method for producing a dental implant.
10. The method of claim 1,

    The coating composition is 2'-deoxyadenosine 5'-monophosphate (DAP), 2'-deoxycytidine 5'-monophosphate (DCP), 4,4'-Diaminostibene-2,2'-disulfonic acid (DASDA), N- Tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid (TAPS) or a salt thereof, characterized in that it comprises a dental implant manufacturing method.

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