KR100983019B1 - Organic-inorganic hybrid complex, method for preparing the organic-inorganic hybrid complex, and artificial hard tissue comprising the same - Google Patents

Abstract

An organic-inorganic hybrid composite, a method for preparing the same, and an artificial hard tissue including the same are provided.

The method for preparing an organic-inorganic hybrid composite according to the present invention includes contacting an anion-containing polyester ionomer with a similar biological solution containing calcium and phosphoric acid, and the method for preparing an organic-inorganic hybrid composite according to the present invention has a complicated multi-step configuration. The organic-inorganic hybrid composite can be prepared by a relatively simple process without. Furthermore, in the organic-inorganic hybrid composite prepared according to the present invention, the hydroxide apatite laminated on the polyester has a crystal structure that is effectively bonded and grown with the polyester, thereby exhibiting excellent activity in vivo and excellent physical properties. have.

Description

ORGANIC-INORGANIC HYBRID COMPLEX, METHOD FOR PREPARING THE ORGANIC-INORGANIC HYBRID COMPLEX, AND ARTIFICIAL HARD TISSUE COMPRISING THE SAME}

 The present invention relates to an organic-inorganic hybrid complex, a method for manufacturing the same, and an artificial hard tissue including the same, and more particularly, to an organic-inorganic hybrid complex exhibiting properties similar to hard tissues of a human body, a manufacturing method capable of economically manufacturing the same, and the same. It relates to an artificial hard tissue containing.

Research into artificial tissues that are similar to hard tissues such as bones, teeth, and joints of the human body, and which can be used chemically and mechanically as well as without biological rejection has been continued.

The history first began with metallic materials with good mechanical properties, such as stainless steel or chromium-cobalt steel. However, metal materials with excellent mechanical properties have problems such as metal ions eluting as metal surfaces are gradually corroded by body fluids in the corrosive body, and these metal ions spread to various organs in the body to cause inflammation or cancer. there was.

In addition, since there is no affinity with living organisms, a biological foreign body reaction such as a fibrous coating occurs on the surface of the metal and does not bind with surrounding bones, but rather destroys the surrounding bones. there was.

In order to solve the problems of the metal material, a study on ceramics was conducted, and alumina (Al ₂ O ₃ ) and zirconia (ZrO ₂ ), which are structural ceramics having excellent mechanical properties, were mainly studied. However, these ceramics do not have the same problem of corrosion as the metal material, but there is a new problem that a fibrous coating is formed at the interface without directly bonding with bones.

On the other hand, a bio-ceramic that bonds directly with bone has been developed, such as calcium phosphate compounds including calcium oxide-silica (CaO-SiO ₂ ) -based bioactive glass and crystallized glass, apatite, an inorganic component of bone. These materials bind directly to bones at the interface and do not cause inflammatory reactions or foreign body reactions, but because of their low mechanical strength and poor fracture toughness, these materials themselves require high stresses such as teeth and hip joints. Artificial bone materials that require high mechanical strength and fracture toughness are inadequate. Therefore, the apatite itself is used in a limited area that does not require high mechanical strength, such as the ear bones. In addition, a method of using apatite-wollastonite (CaOSiO ₂ ) crystallized glass (A / W crystallized glass) instead of metal has been proposed, but the mechanical strength is slightly higher than that of the apatite sintered body, but the overall mechanical strength is still insufficient, so it is widely used. Do not.

In order to solve the above problems, relatively recent attempts have been made to overcome the shortcomings of metals by coating bioactive ceramics on metallic materials. That is, it is a method of utilizing the biocompatibility and bioactivity characteristics of apatite while having mechanical strength and fracture toughness of the metal. However, there is a known disadvantage that the adhesion strength between the ceramic coating layer and the metal material is low so that the coating layer does not withstand repeated loads when implanted in the body, and the peeling of the coating layer subsequently causes inflammatory reactions and tissue necrosis. It must be restrained.

In an attempt to solve the problem of peeling due to the difference in mechanical and thermal properties between the metal material and the apatite coating layer, a method of coating apatite on a ceramic substrate is actively proposed. No. 5,077,079 is coated on the ceramic surface alone or mixed with calcium metaphosphate (CaP ₂ O ₆ ) or mixed with calcium pyrophosphate (Ca ₂ P ₂ O ₇ ) and heat-treated to fuse the ceramic substrate. To form an intermediate layer, and then to coat a slurry containing a mixture of dicalcium phosphate and tricalcium phosphate (TCP, Ca ₃ (PO ₄ ) ₂ ) and heat-treat it to form a dense coating. Doing.

In addition, US Pat. No. 5,472,734 describes coating apatite by coating calcium salt on an alumina ceramic substrate and depositing it in a phosphate solution containing phosphate and modifying it into apatite, and Korean Patent Application Publication No. 2000-18897 discloses apatite hydroxide. A thin film coating method, comprising: installing apatite hydroxide added with calcium-based compound and a material to be coated with hydroxide apatite in a chamber equipped with an electron gun and an ion gun, and evacuating the chamber, and then vacuuming the inside of the chamber with an ion gun. It is characterized in that the ion film is removed to remove the oxide film of the material surface layer, and the electron beam is injected into the apatite hydroxide with an electron gun to deposit it on the material surface while the hydroxide apatite is evaporated.

In addition, a method of coating apatite on a ceramic material such as zirconia or alumina is disclosed in Korean Patent Publication No. 10-424,910. The patent relates to a coating method of a bioactive ceramic, in particular, a bioactive ceramic powder, which is used as an artificial biomaterial, is dispersed in a solvent with a binder to form a slurry and then coated on an oxide ceramic substrate, and the coating method described above. It relates to an artificial tooth or bone graft material.

In addition, Korean Laid-Open Patent Publication No. 10-2004-1325 discloses a method of suppressing a reaction between apatite hydroxide and a secondary phase by substituting hydroxide ions of apatite hydroxide with fluorine ions. And preventing the decomposition of unwanted substances such as tricalcium phosphate, tetracalcium phosphate, calcium oxide, etc., and ultimately preventing the deterioration of the biomechanical properties of the apatite complex.

In addition, Japanese Patent Application Laid-Open No. 6-60069 deals with apatite-coated composite materials and a method of manufacturing the same, and more specifically, mixed meta calcium phosphate and tetracalcium phosphate to make a slurry and apply it through water vapor. After the high temperature heat treatment was to be related to the apatite coating composite material and the method for producing a β-TCP with the hydroxide apatite to thereby obtain a more dense coating layer.

However, the above-described methods require both sintering and complex heat treatment, and thus have disadvantages in that the manufacturing process is complicated and inexpensive. In addition, all of the above processes have a disadvantage in that it is difficult to form a 100% apatite coating layer.

The first problem to be solved by the present invention is to provide an organic-inorganic hybrid composite that can produce an organic-inorganic hybrid composite exhibiting excellent properties as artificial hard tissue in a simpler and more effective way.

The second problem to be solved by the present invention is to provide an organic-inorganic hybrid complex exhibiting excellent properties when used as an artificial hard tissue.

The third problem to be solved by the present invention is to provide an artificial hard tissue exhibiting excellent properties in vivo.

In order to solve the first problem, the present invention provides a method for preparing an organic-inorganic hybrid composite comprising the step of contacting an anion-containing polyester ionomer to a similar biological solution containing calcium and phosphoric acid, the anion is sulfonic acid or carboxylic acid It may be an anion. In addition, the manufacturing method of the organic-inorganic hybrid composite according to the present invention further comprises the step of maintaining the contact state of the polyester ionomer and the analogous biological solution after the contact for 200 to 400 hours, wherein the analogous biological solution is organic-inorganic Maintain a temperature of 30 to 40 ℃ during the manufacturing process of the hybrid composite.

One embodiment of the present invention provides a polyester ionomer comprising a monomer represented by the following formula (1) and (2),

In the above formula 1 and 2,

R ¹ is a sulfonic acid or carboxylic acid anion, R ² is alkylene having 2 to 4 carbon atoms or polyoxyalkylene having a number average molecular weight of 200 to 2000, wherein the alkylene of the polyoxyalkylene is 2 to 4 carbon atoms. Alkylene, m is an integer from 1 to 3, n is an integer from 2 to 4. In addition, in one embodiment of the present invention, the molar ratio of the monomer represented by Formula 1 and the monomer represented by Formula 2 is 1.0: 99.0 to 5.0: 95.0, and the analogous biological solution is NaCl 1 to 5 M, KCl to 0.01 to 0.1 M, CaCl ₂ 0.01-0.1 M, MgCl ₂ 0.01-0.1 M, NaHCO ₃ 0.01-0.15 M, K ₂ HPO ₄ 0.005-0.05 M, Na ₂ SO ₄ 0.005-0.05 M, (CH ₂ OH) ₃ CNH ₂ 0.1 to 1 M, and 0.01 to 0.5 M HCl.

In order to solve the second problem, the present invention provides an organic-inorganic hybrid composite comprising a polyester ionomer and an hydroxide apatite containing anion, wherein the anion may be a sulfonic acid or a carboxylic acid anion.

One embodiment of the present invention provides a polyester ionomer comprising a monomer represented by Formula 1 and 2, wherein the molar ratio of the monomer of Formula 1 and the monomer of Formula 2 is 1.0: 99.0 to 5.0: 95.0 .

In addition, the organic-inorganic hybrid composite according to the present invention has a structure in which the hydroxide apatite is laminated on the polyester surface.

In order to solve the third problem, the present invention provides an artificial hard tissue comprising the aforementioned organic-inorganic hybrid complex, wherein the artificial hard tissue may be an artificial joint, an artificial bone, or an artificial root.

The organic-inorganic hybrid composite manufacturing method according to the present invention can be produced by a relatively simple process without a complex multi-step configuration. Furthermore, in the organic-inorganic hybrid composite prepared according to the present invention, the hydroxide apatite laminated on the polyester has a crystal structure that is effectively bonded and grown with the polyester, thereby exhibiting excellent activity in vivo and excellent physical properties. have.

In order to solve the first problem, the present invention provides a method for preparing an organic-inorganic hybrid composite comprising contacting an anion-containing polyester ionomer with a similar biological solution containing calcium and phosphoric acid.

In the present invention, an anion capable of growing crystals of apatite hydroxide (Ca ₁₀ (PO 4) ₆ (OH) ₂ ) in the polyester, in particular an anion such as sulfonic acid or carboxylic acid, is introduced into the polyester, thereby binding to calcium contained in the contact solution. , especially the ion binding is derived as a result polyanion combined with calcium in the ester is phosphate anion (PO4 ^{3 -)} with the lapse of time could be self-grown on the surface of the polyester ionomer hydroxide apatite in combination with reactions that As a result, the present invention has been found to be surprising, and thus, the present invention provides a composite prepared by the organic-inorganic hybrid composite manufacturing method according to the present invention. To the poly to compensate for the disadvantages It has a structure in which steers are bonded (ionically bonded) in a very effective manner, and furthermore, they are manufactured according to a biomimetic method, and thus are very stable when used for a long time in vivo. Unlike the method of the organic-inorganic composite manufacturing method according to the present invention has the advantage that can be prepared an organic-inorganic hybrid composite of excellent properties by a simple method of contacting the polyester to the solution.

The organic-inorganic composite manufacturing method according to the invention further comprises the step of maintaining the contact state of the analogous biological solution and the polyester ionomer 200 to 400 hours, if it is shorter than the time it is difficult to achieve a sufficient crystal growth of apatite hydroxide If it is longer than this time, it is uneconomical. However, the contact time may be changed depending on the solution composition or the desired production amount, which is also within the scope of the present invention.

In one embodiment of the present invention, the polyester ionomer is a copolymer including the monomers represented by Formulas 1 and 2, wherein Formula 1 is an anionic structure capable of ionic bonding with calcium as described above, preferably sulfonic acid Or anions of carboxylic acids. However, the scope of the present invention is not limited to the sulfonic acid or carboxylic acid anion, and any anion that can combine with calcium to provide a crystal growth environment of hydroxide apatite falls within the scope of the present invention.

In the polyester ionomer according to the present invention, the molar ratio of the monomer represented by Chemical Formula 1 and the monomer represented by Chemical Formula 2 is preferably 1.0: 99.0 to 5.0: 95.0, if the monomer of Chemical Formula 1 containing an anion If it is less than the above range, it is difficult to provide a growth site (combination of anion and calcium ions) in which the hydroxide apatite can sufficiently crystallize, and in the case of more than the above numerical range, not only mechanical deterioration occurs due to aggregation of ion aggregates, but also However, there is a problem in that the binding force with calcium ions required in the early stage of apatite growth is rather reduced. In addition, a similar biological solution in which the polyester contacts to form hydroxide apatite on the polyester is NaCl 1 to 5 M, KCl 0.01 to 0.1 M, CaCl ₂ 0.01 to 0.1 M, MgCl ₂ 0.01 to 0.1 M, NaHCO ₃ 0.01 to 0.15 M, K ₂ HPO ₄ 0.005 to 0.05 M, Na ₂ SO ₄ 0.005 to 0.05 M, (CH ₂ OH) ₃ CNH ₂ 0.1 to 1 M, and HCl 0.01 to 0.5 M. That is, the organic-inorganic hybrid composite manufacturing method according to the present invention contains calcium and phosphate anion, and because the organic-inorganic hybrid composite is prepared in a solution environment similar to human biological solution (plasma), it is excellent in vivo, which is the actual use environment It may have stability. However, the composition and the concentration range of the solution is similar to the solution conditions in vivo, it is only one example of the conditions that can form the hydroxide apatite in the anion-containing polyester, the present invention is not limited thereto.

The temperature of the analogous biological solution is preferably maintained at a temperature of 30 to 40 ℃ in contact with the polyester in order to produce a composite under the same conditions in vivo. If it is out of the above range, there is a risk that the composition or physical property change of the complex according to another by-product reaction when used in the living body.

The present invention provides an organic-inorganic hybrid composite comprising a polyester ionomer and a hydroxide apatite containing sulfonic acid or carboxylic acid anion in order to solve the second problem. In one embodiment of the present invention, the hydroxide apatite is laminated on the polyester ionomer, wherein the hydroxide apatite has a structure in which the hydroxide apatite is ionically bonded with the sulfonic acid or carboxylic acid anion introduced into the polyester ionomer.

In one embodiment of the present invention, the polyester ionomer is a copolymer including the monomers represented by Formulas 1 and 2, and the molar ratio of the monomers represented by Formula 1 and the monomers represented by Formula 2 is 1.0: 99.0. To 5.0: 95.0. As described above, when the monomer of Formula 1 containing an anion is less than the above range, it is difficult to provide a growth site (combination of anion and calcium ion) in which the hydroxide apatite can sufficiently crystallize, and when more than the numerical range, ion aggregates Due to the agglomeration of each other, not only the mechanical properties decrease, but also the binding strength with calcium ions necessary for the initial growth of apatite is rather problematic.

The present invention provides an artificial hard tissue comprising the organic-inorganic hybrid complex in order to solve the third problem, examples of the artificial hard tissue may be artificial joints, artificial bones, or artificial root, artificial hard tissue of the present invention Is not limited to this.

Hereinafter, the present invention will be described in more detail with reference to the following examples and drawings.

Example  One

Example  1-1

Polyester Ionomer  Produce

3.74 g (0.015 mol) of sulfonated dmethyl fumarate (SDMF), 55.26 g (0.485 mol) of succinic acid, and 1,4 substituted in the form of a salt of sodium and sulfonate ions in a two-necked round flask 54 g (0.6 mol) of butanediol were added, and a small amount of titanium tetrabutoxide, which was a catalyst, was added at about 100 ° C while gradually increasing the temperature, and the esterification reaction was carried out while raising the temperature to 190 ° C. Water generated during the ester reaction was separated out of the reaction system using a distillation apparatus. The ester reaction was terminated after 120 minutes when no more water was distilled off. After the esterification is completed, the esterification reaction is cooled to room temperature, slowly reduced in pressure and slowly heated up to 215 ° C. under high vacuum (0.1 torr or less), followed by a polycondensation reaction for 210 minutes to include ionic groups. A polyester ionomer having a content of 3 mol% of units (hereinafter referred to as 'ion repeating units') was prepared.

In addition, the molecular weight and viscosity of the prepared polyester ionomer were measured and shown in Table 1 below.

Sample GPC [η] (g / dL) Mn X 10 ^-4 M _w / M _n Comparative example 4.7 1.7 0.99 Example 2 4.6 1.8 0.97 Example 1 - - 0.94 Example 3 - - 0.93

In the GPC measurement of Example 1 and Example 5, the ion group was adsorbed on the column, so that accurate molecular weight measurement was impossible, but it was determined that the viscosity values were similar to those of Example 2 because the viscosity values were similar.

Example  1-2

Preparation of Analogous Biological Solution

In a flask containing 800 ml of an aqueous HCl solution having a concentration of 0.36 M and 0.4 mol of TRIS [(CH ₂ OH) ₃ CNH ₂ ], NaCl, KCl, MgCl _{2 ,} NaHCO _{3, and} K ₂ were added in the same amounts as described in Table 2 below. HPO _{4 ,} Na ₂ SO _{4 ,} and CaCl ₂ were sequentially added and mixed.

ingredient Content (mol / L) NaCl 2.74 KCl 0.06 CaCl ₂ 0.05 MgCl ₂ 0.03 NaHCO ₃ 0.0895 K ₂ HPO ₄ 0.02 Na ₂ SO ₄ 0.01 (CH ₂ OH) ₃ CNH ₂ 0.4 HCl 0.36

Subsequently, 200 mL of an aqueous HCl solution having a concentration of 0.36 M was added dropwise while slowly stirring the mixture to prepare a transparent analogous biological solution having a pH of 7.4.

Example  1-3

Organic weapons hybrid  Preparation of the complex

The prepared polyester ionomer was prepared into a 3 cm × 3 cm × 0.25 mm sized film, and then the film was immersed in the analogous biological solution of Example 1-2, which was then heated to 36.5 ° C. for 320 hours. Hydroxyapatite crystals were grown on the surface. Thereafter, the film was washed with water and dried to prepare an organic-inorganic hybrid composite.

Example  2

1.25 g (0.005 mol) of sulfonated dmethyl fumarate and 57.75 g (0.495 mol) of succinic acid are used to prepare a polyester ionomer, and the content of the ion repeating unit is 1 mol%. An organic-inorganic hybrid composite was prepared in the same manner as in Example 1, except that the ionomer was prepared.

Example  3

Polyester with ion repeating unit content of 5 mol% using 6.23 g (0.025 mol) of sulfonated dmethyl fumarate and 52.77 g (0.475 mol) of succinic acid in the production process of polyester ionomer An organic-inorganic hybrid composite was prepared in the same manner as in Example 1, except that the ionomer was prepared.

Comparative example  One

In the manufacturing process of the polyester ionomer, a polyester was prepared without the use of ionic repeating units using 59.0 g (0.5 mol) of succinic acid without using dimethyl fumarate sulfonate. Except for the organic-inorganic hybrid composite was prepared in the same manner as in Example 1.

Experimental Example  One

Nuclear magnetic  Resonance spectrum

Experimental Example  1-1

In order to confirm the structures of the polyester ionomers and polyesters prepared according to Examples 1 to 3 and Comparative Example 1, ¹ H-NMR spectra were measured using an FT-NMR spectrometer (Varian, 300 MHz). At this time, the solvent used in the measurement was used as a reference material CDCl3 containing tetramethylsilane (TMS).

FIG. 1 shows ¹ H-NMR spectra of polyester ionomers prepared according to Examples 1 to 3 and polyesters prepared according to Comparative Example 1. FIG.

Referring to FIG. 1, in the polyester according to Comparative Example 1, main peaks were observed at 4.1, 2.6, and 1.7 ppm, and the area ratios thereof were found to be 1: 1: 1. On the other hand, in the polyester ionomer of Example 1 having an ion repeating unit content of 1 mol%, a new peak appeared at 3.7-3.65 ppm, and in the polyester ionomers of Examples 2 and 3 having an increased content of ion repeating unit It can be seen that the intensity of the peak is increased. It can be seen from these that these peaks are represented by ion repeating units. In addition, it can be confirmed that the ion repeating unit is effectively introduced into the polyester from the fact that the integral ratio of these peaks to methylene hydrogen (-OCOCH ₂ CH ₂ COO-) appearing at 2.6 ppm is proportional to the content of the ion repeating unit in the ionomer.

Experimental Example  1-2

²³ Na solid state NMR

²³ Na solidstate NMR spectra were measured using a super conduction FT-NMR spectrometer (Bruker, AVANCE DSX-400). The measurement conditions were 105.805 MHz, the frequency axis was set using an external NaCl reference, the rotation speed was 4000 / sec in the analysis, and a 5 second pulse delay was applied to obtain a fully relaxed spectrum. Pulse length and pulse power were 2 US and 120 DB, respectively.

FIG. 2 shows ²³ Na solid state NMR spectra of SDMF and polyester ionomers prepared according to Examples 1-3.

Referring to FIG. 2, it can be seen that as the ionization of the polyester ionomer increases, electrostatic crosslinking due to the interaction of sodium ions increases, which appears in the form of multiplets.

Experimental Example  2

Rheological  characteristic

Melting properties of the polyester ionomer and polyester were measured using an advanced rheometric expansion system (ARES) apparatus (Rheometric Scientific). For the measurement, a horizontal plate having a diameter of 12.5 mm was used, the distance between the plates was 1.0 mm, the measurement frequency was 0.05 to 500 rad / s, and the measurement temperature was 150 ° C.

Figure 3 shows a melt viscosity graph of the polyester ionomer prepared according to Examples 1 to 3 and the polyester prepared according to Comparative Example 1.

Referring to FIG. 3, the polyester prepared according to Comparative Example 1 exhibited a typical thinning phenomenon in the high frequency region. On the other hand, the polyester ionomers according to Examples 1 to 3 showed high viscosity in the low frequency region, and it can be seen that this tendency is more pronounced, especially as the content of the ion repeating unit is increased.

In general, when the melt viscosity of the polymer is high, it means that the resistance to flow is high, and this phenomenon may occur when chemical bonds or specific interactions exist in the polymer. Accordingly, it can be seen that the polyester ionomer has a higher viscosity value with increasing ionization, and the degree of crosslinking between ionic groups depends on the result of intermolecular ion-pair aggregation in the polymer matrix. see.

In addition, while the polyester according to Comparative Example 1 maintains a certain viscosity value, it can be seen that the melt viscosity value in the polyester ionomer according to Examples 1 to 3 greatly decreases with increasing frequency. This seems to be a phenomenon caused by breaking physical crosslinking of the polyester ionomer as the shear force increases.

Experimental Example  3

Polyester Ionomer  And polyester of  Structural analysis

The structure of the polyester ionomer and polyester was analyzed using an X-ray diffraction analyzer (Rigaku Denki D-Max2000). In this case, the measurement conditions were 40 kV, 100 mA, and the measurement was performed using an 18-kW rotary anode X-ray generator equipped with a rotary copper target anode as an X-ray source, and a polyester ionomer prepared according to Examples 1 to 3. And the polyester prepared according to Comparative Example 1 was prepared in powder form to measure the X-ray diffraction pattern, it was measured at a scan rate of 5 ^o / min in the range of 2θ 5-40 ^o .

4 is a graph showing a wide-angle X-ray diffraction pattern of the polyester ionomer prepared according to Examples 1 to 3 and the polyester prepared according to Comparative Example 1. FIG.

Referring to FIG. 4, the characteristic peaks of the polyesters according to Comparative Example 1 are shown at 19.3 ^o , 21.7 ^o , 22.4 ^o , and 28.7 ^o , which are (020), (021), (110), and (111), respectively. ) Indicates a crystal plane. In addition, in the polyester ionomers according to Examples 1 to 3, no peak other than the characteristic peaks of the polyesters of Comparative Example 1 was observed, from which d-spacing and diffraction of the polyester ionomers according to the present invention. It can be seen that the properties are not significantly different from general polyester, and have a monoclinic crystal structure, and the ionic group of the polyester ionomer is excluded from the crystal region of the polyester. Therefore, when the content of the ion group is 3 to 5 mol%, efficient mechanical properties can be obtained without changing or changing the crystal structure of the existing polyester. It was confirmed that the polymerization did not occur, or it took a very long time, and in fact, the mechanical properties also decreased considerably.

Experimental Example  4

Hydroxide apatite ( HAp Decision analysis

Wide-angle X-ray diffraction of the surface of the polyester ionomer prepared according to Examples 1 to 3 and the polyester prepared according to Comparative Example 1 was measured at a scan rate of 5 ^o / min in the range of 2θ = 10-60 ^o . It was.

5 is a wide-angle X-ray diffraction graph of pure HAp crystals showing the change in wide-angle X-ray diffraction over time of the biological solution treatment of the organic-inorganic hybrid composite prepared according to Example 3. FIG.

Referring to FIG. 5, in the wide-angle X-ray diffraction graph of pure HAp crystals, a characteristic peak of HAp crystals appears at 32 ^° , which corresponds to the (211) crystal plane of hexagonal HAp crystals. In addition, although the characteristic peak of the HAp crystal was not observed until 40 hours, the initial stage of the similar biological solution treatment, it was found that the characteristic peak of the HAp crystal began to appear in the vicinity of 32 ^° after 80 hours. Thereafter, the characteristic peak of the HAp crystals increases with time, from which it can be seen that HAp crystals are growing on the surface of the polyester ionomer.

6a to 6c are SEM images of the organic-inorganic hybrid composite prepared according to Example 3 over time of treatment with a biological solution. When the similar biological solution treatment time is 80 hours (FIG. 6B), it was confirmed that HAp particles were formed on the surface of the polyester ionomer film, and as the treatment time was increased, the size of the HAp particles was increased, and they were regularly dispersed. It was confirmed (320 hours elapsed, Fig. 6c). This phenomenon can be interpreted as follows.

Polyester ionomers are similar when treated with biological solutions SO ^{3 -} of a cation of Na ⁺ group Na ⁺ is causing an ion exchange reaction with the cation of H ₃ O ⁺ present in similar biological solution, so that the polyester ionomer and biological SO ^{3 -} H ⁺ is generated in the ion group in the contact area of the solution, and increased Na ⁺ ions in the analogous biological solution raise the pH of the analogous biological solution. The SO ^{3 -} H ⁺ group of the polyester ionomer interacts with the calcium ions in the analogous biological solution to form calcium sulfonates, which, together with the phosphate ions contained in the analogous biological solution, are present on the surface of the polyester ionomer. Form HAp. That is, the formation of calcium phosphate is due to the electrostatic interaction between positively charged calcium sulfonate and negatively charged phosphate, and as the contact time of the polyester ionomer and the analogous biological solution increases, HAp is the calcium in the analogous biological solution. It can be seen that the ions and phosphate ions are absorbed and grown outward of the polyester ionomer (see SEM photographs of FIGS. 5 and 6). It can also be seen from this that the ionic groups present in the polyester ionomer play an important role in the production of HAp crystals.

7 shows a wide-angle X-ray diffraction pattern of a polyester prepared according to Comparative Example 1 and a polyester ionomer prepared according to Examples 1 to 3. FIG.

Referring to FIG. 7, it can be seen that as the ion group content of the polyester ionomer increases, the HAp peak (arrow of FIG. 7) also increases, from which the formation and growth of HAp crystals is proportional to the degree of ionization of the polyester ionomer. It can be seen that. On the other hand, in the case of the polyester of Comparative Example 1, in which no anion was introduced, the fact that the HAp peak did not appear clearly indicates that the polyester ionomer according to the present invention is very advantageous for HAp growth and formation.

8 is a schematic diagram showing the mechanism of HAp crystal growth occurring on the surface of the polyester ionomer.

Referring to Figure 8, the action is anionic groups present in the polyester ionomer as the functional group capable of binding with abundant Ca ^{2 +} ions present in the similar biological solution, as well as to increase the interfacial bonding between the HAp as polyester, HAp It can be seen that it serves as an active site for growing crystals.

Experimental Example  4

Thermogravimetric analysis Thermogravimetric Analysis , TGA )

The content of hydroxyapatite (HAp) contained in the organic-inorganic hybrid composite was measured by thermogravimetric analysis. PYRIS TGA (PerkinElmer, Norwalk, CT, USA) was used for the measurement, and the weight change was measured by increasing the temperature at a rate of 20 ℃ / min in the temperature range of 20-1000 ℃.

9 is a TGA curve of a polyester prepared according to Comparative Example 1 and a polyester ionomer prepared according to Examples 1 to 3. FIG.

Referring to FIG. 9, it can be seen that the polyester according to Comparative Example 1 remains about 0.35% by weight, while the weight of the residue also increases as the content of ionic groups of the polyester ionomer increases. In addition, in the case of the polyester ionomer of Example 3 having an ion repeating unit content of 5 mol%, the residue content was 2.46 wt%, from which it can be seen that the content of HAp increases with the content of the ion group.

FIG. 10 shows the relationship between the content of ionic repeat units present in the polyester ionomer and the weight of the residue, and from FIG. 10 a linear correspondence relationship corresponding to Y = 0.36 + 0.40X between the content of the ionic repeat units and the weight of the residue. It was confirmed that there is, and the reliability of the correspondence was very high as 0.9889. Therefore, it can be seen from the above result that the ion group of the polyester ionomer acts as an active point of HAp crystal formation and also plays a leading role in the growth of HAp crystals.

Experimental Example  5

Infrared spectrum ( FT - IR )

Fourier transform infrared (FT-IR) spectra for organic-inorganic hybrid composites are measured using an IFS 88-IR spectrometer (Bruker AXS GmbH, Karlsruhe, Germany), with a measured wavenumber range of 4000 500 cm ^-1 , 4 cm ^-1 resolution, with 16 scans superimposed on each sample.

FIG. 11 is a view showing FT-IR spectra of a polyester prepared according to Comparative Example 1 and a polyester ionomer prepared according to Examples 1 and 3. FIG.

11, the third embodiment, if the polyester ionomer, the PO ₄ ^{3 -} the characteristic bands for the asymmetric cast retching of 1038cm ^- was observed at ^1, as in these results experiment from Example 4 of the TGA results of this invention It can be seen that the anion group contained in the polyester ionomer acts as an active point of HAp crystal formation, and also plays a leading role in the growth of HAp crystals. Furthermore, the results of this experimental example are consistent with wide-angle X-ray diffraction.

Experimental Example  6

Scanning electron microscope Scanning electron microscopy , SEM )

After the organic-inorganic hybrid composite was dried at room temperature under a nitrogen atmosphere, Au-Pd coating was performed by ion sputtering, and the surface was observed by using a field emission scanning electron microscope (S-3000N, HITACHI). .

12A to 12C are SEM images of organic-inorganic hybrid composites prepared according to Examples 1 to 3, respectively.

Referring to FIG. 12A, in the case of Example 1, it is shown that HAp crystals are successfully formed. Referring to FIGS. 12B and 12C, as in Examples 2 and 3, as the content of the ion repeating unit increases, more HAp is formed. It can be seen that crystals form on the surface of the polyester ionomer. This phenomenon can be interpreted that the more ion groups present in the polyester ionomer, the more the interaction between calcium ions and phosphate ions in the analogous biological solution increases, making it easier and faster to produce HAp crystals. have. In addition, in the SEM photographs of Examples 2 and 3, not only HAp crystals present in the bulk phase, but also voids exist in the crystals. These pores allow the surrounding tissue to grow in and are also well suited to aiding bone formation. Therefore, it can be seen from the above results that the ion repeating unit in the polyester ionomer is a factor that determines the production of HAp, the organic-inorganic hybrid composite of the present invention can be said to be a new material that can be applied in the field of hard tissue regeneration.

1 is a ¹ H-NMR spectrum of the polyester ionomer prepared according to Examples 1 to 3 and the polyester prepared according to Comparative Example 1.

FIG. 2 is a ²³ Na solid state NMR spectrum of a polyester ionomer prepared according to Examples 1 to 3 with SDMF. FIG.

Figure 3 is a melt viscosity graph of the polyester ionomer prepared according to Examples 1 to 3 and the polyester prepared according to Comparative Example 1.

4 is a wide-angle X-ray diffraction pattern of the polyester ionomer prepared according to Examples 1 to 3 and the polyester prepared according to Comparative Example 1. FIG.

FIG. 5 is a wide-angle X-ray diffraction pattern of a biological solution treatment time course of the organic-inorganic hybrid composite prepared in Example 3. FIG.

6a to 6c are SEM images of the biological solution treatment time course of the organic-inorganic hybrid composite prepared according to Example 3.

7 is a wide-angle X-ray diffraction pattern of the polyester prepared according to Comparative Example 1 and the polyester ionomer prepared according to Examples 1 to 3. FIG.

8 is a schematic diagram showing an example of a mechanism of HAp crystal growth occurring on the surface of a polyester ionomer.

9 is a TGA curve of the polyester prepared according to Comparative Example 1 and the polyester ionomer prepared according to Examples 1 to 3.

Figure 10 is a weight proportionality of the residues according to the content of the ion repeating units present in the polyester ionomer.

FIG. 11 is an FT-IR spectrum of a polyester prepared according to Comparative Example 1 and a polyester ionomer prepared according to Examples 1 and 3. FIG.

12a to 12c is an SEM image of the organic-inorganic hybrid composite prepared according to Examples 1 to 3.

Claims (14)

A method for producing an organic-inorganic hybrid composite, comprising contacting an anion-containing polyester ionomer with a similar biological solution containing calcium and phosphate ions. The method of claim 1, The anion is a method for producing an organic-inorganic hybrid composite, characterized in that the sulfonic acid or carboxylic acid anion. The method of claim 1, And maintaining the contact state of the polyester ionomer and the analogous biological solution after the contact for 200 to 400 hours. The method of claim 1, The analogous biological solution is a method for producing a hybrid composite, characterized in that to maintain a temperature of 30 to 40 ℃ during the manufacturing process of the organic-inorganic hybrid composite. The method of claim 1, The polyester ionomer production method of an organic-inorganic hybrid composite, characterized in that it comprises a monomer represented by the following formula 1 and formula 2:

(One)

(2) (In Formulas 1 and 2, R ¹ is sulfonic acid or carboxylic acid anion, R ² is alkylene having 2 to 4 carbon atoms or polyoxyalkylene having a number average molecular weight of 200 to 2000, wherein the alkylene of the polyoxyalkylene includes alkylene having 2 to 4 carbon atoms, m is an integer of 1 to 3, n is an integer from 2 to 4) The method of claim 5, The molar ratio of the monomer represented by Formula 1 and the monomer represented by Formula 2 is 1.0: 99.0 to 5.0: 95.0 method for producing an organic-inorganic hybrid composite. The method of claim 1, The analogous biological solution is NaCl 1 to 5 M, KCl 0.01 to 0.1 M, CaCl ₂ 0.01 to 0.1 M, MgCl ₂ 0.01 to 0.1 M, NaHCO ₃ 0.01 to 0.15 M, K ₂ HPO ₄ 0.005 to 0.05 M, Na ₂ SO ₄ 0.005 to 0.05 M, (CH ₂ OH) ₃ CNH ₂ 0.1 to 1 M, and HCl 0.01 to 0.5 M method for producing an organic-inorganic hybrid composite. delete delete In the organic-inorganic hybrid composite containing an anion-containing polyester ionomer and hydroxide apatite, The organic-inorganic hybrid composite, characterized in that the polyester ionomer comprises a monomer represented by the following formula 1 and formula 2:

(One)

(2) (In Formulas 1 and 2, R ¹ is sulfonic acid or carboxylic acid anion, R ² is alkylene having 2 to 4 carbon atoms or polyoxyalkylene having a number average molecular weight of 200 to 2000, wherein the alkylene of the polyoxyalkylene includes alkylene having 2 to 4 carbon atoms, m is an integer of 1 to 3, n is an integer from 2 to 4) The method of claim 10, The organic-inorganic hybrid composite, characterized in that the molar ratio of the monomer of Formula 1 and the monomer of Formula 2 is 1.0: 99.0 to 5.0: 95.0. The method of claim 10, The hydroxide apatite is organic-inorganic hybrid composite, characterized in that laminated on the polyester ionomer. An artificial hard tissue comprising the organic-inorganic hybrid complex according to any one of claims 10 to 12. The method of claim 13, The artificial hard tissue is an artificial hard tissue, characterized in that the artificial joints, artificial bones, or artificial tooth root.

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