KR101604584B1 - Composite comprising hydroxyapatite, chitosan or its derivative, and catechol or its derivative and use thereof - Google Patents

Abstract

The present invention relates to a composite comprising hydroxyapatite, chitosan, chitin or a derivative thereof and catechol or derivatives thereof, an organic reinforcing material composition comprising said complex, a product made of said organic reinforcing material composition, And a manufacturing method thereof. The complex provided by the present invention is a material to which catechol or catechol derivatives are added and is harmless to the human body and exhibits a strong mechanical strength and can be used as a variety of biological materials such as artificial tendons, artificial ligaments, artificial dental materials, But the present invention is not limited thereto.

Description

TECHNICAL FIELD The present invention relates to a composite containing hydroxyapatite, chitosan or a derivative thereof, and catechol or a derivative thereof, and a use thereof. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition containing hydroxyapatite,

The present invention relates to a composite comprising hydroxyapatite, chitin, chitosan or a derivative thereof and catechol or derivatives thereof, an organic reinforcing material composition comprising said complex, an article made of said organic reinforcing material composition, And a manufacturing method thereof.

In terms of anatomical biology, the material that constitutes the bone of a vertebrate is composed of cells (osteoblasts, osteocytes, and osteocytes) constituting the bone and hard tissues secreted by the cells. A material constituting the bone in chemical terms are inorganic comprises from about 70 wt% (most of hydroxyapatite _{(HA), Ca 5 (PO} 4) 3 OH) and the remainder organic material constituting the 30 wt% (mostly collagen Type I). The vertebrate bones become a source of complexity with a certain degree of toughness through a combination of brittle hydroxyapatite and tough collagen.

Human bones are often damaged by external impacts of various pathways or internal diseases in humans, and various methods have been devised to regenerate damaged bones. One of the methods is sterilization of the bones of cattle and pigs, but it needs to be replaced with new materials because of the inflammation and rejection in the human body when used. Although synthetic hydroxyapatite (Synthetic HA), native collagen, and recombinant collagen are synthesized, hydroxyapatite synthesized has a fracture property and needs to be combined with organic materials having toughness. Native collagen Although it can be extracted from the rat's tail, it is difficult to use because it can cause a rejection reaction of the human body. Since recombinant collagen is difficult to have poly-proline type II possessed by native collagen, .

Chitin or chitosan has been proposed as a material to form a complex with hydroxyapatite to regenerate bone. Chitin and chitosan are natural polysaccharides that are tasteless and odorless. Chitin is a polysaccharide polymer substance composed of N-acetyl-D-glucosamine units bound to each other in an uncoupled state. Chitosan is a polysaccharide polymer substance composed of chitin- to be. Since chitin and chitosan are natural components, they are well-suited for living bodies and have no enzymes for decomposing chitin or chitosan in the human body. Therefore, they can be used in a variety of medical fields such as artificial skin, surgical suture, artificial dialysis membrane, Can be used.

The present invention provides a composite comprising hydroxyapatite, chitin, chitosan, or a derivative thereof, and catechol or a derivative thereof, which is harmless to the human body and has a strong mechanical strength.

Another example provides an organic reinforcing material composition comprising the composite.

Another example provides a product made from the organic reinforcing material composition.

Another example provides a method of making the composite.

The invention relates to hydroxyapatite; Chitosan, chitin, or a mixture thereof; And at least one catechol or catechol derivative selected from the group consisting of catechol, dopamine, dopa (DOPA) and methyl catechol; A composite comprising the composite, an organic reinforcing material composition comprising the composite, a product made of the organic reinforcing material composition, and a method of making the composite.

The present inventors have found that when one or more catechol or catechol derivatives selected from the group consisting of hydroxyapatite and chitosan and / or chitin ecatechol, dopamine, dopa, and methylcatechol are added, a material which is harmless to the human body and has enhanced strength And the present invention has been completed.

Such a composite contains a catechol or catechol derivative and is harmless to the human body and has an advantage of exhibiting a strong mechanical strength. In particular, the complex may be provided as a material for artificial tendons and artificial ligaments. Artificial tendons and artificial ligaments have a high strength so as to bridge the skeleton and muscles in place of these tissues when the tendons and ligaments are destroyed. When a new tissue is formed and is no longer needed, High conformity is good.

Hereinafter, the present invention will be described in detail.

Compositions in accordance with an exemplary embodiment of the present invention include hydroxyapatite; Chitosan, chitin, or a mixture thereof; And one or more catechol or catechol derivatives selected from the group consisting of catechol, dopamine, dopa (DOPA), and methyl catechol.

Hydroxyapatite has the same structure as the main constituent of bones and teeth, and is excellent in biocompatibility and has excellent biocompatibility that can be easily incorporated into bone or skin tissue.

The complex according to the present invention comprises at least one member selected from the group consisting of chitin or a derivative thereof, and may specifically include chitin, chitosan, and a mixture thereof. The above-mentioned chitin and chitosan are abundant in nature such as insects and shells of arthropods such as crustaceans and have various advantages such as biodegradability, antiviral property, wound healing ability, It is a material suitable as a material. The chitin and chitosan may have a molecular weight of about 50,000 or more, 200,000 or more, 600,000 or more, or 1,000,000 or more, such as 1,000,000 to 200,000,000, but the present invention is not limited thereto.

The complex according to the present invention includes at least one member selected from the group consisting of catechol and catechol derivatives, and specifically includes at least one member selected from the group consisting of catechol, dopamine, dopa (DOPA) and methylcatechol . The catechol and catechol derivatives are compounds known to be harmless to humans (Ku et al, Biomaterails, 31, 2535-41, 2010), and catechol is a structure in which the OH group of the benzene ring is attached to the oligo- The unpaired electron pair of molecules has the ability to form crosslinks in the form of coordination bonds, covalent bonds, ionic bonds, etc. on molecules having electrophilic properties in the periphery. In order to achieve the desired physical properties (e.g., appropriate porosity, etc.) of the desired complex, the catechol derivative is preferably a compound having both catechol functionality and amine functionality, for example, selected from the group consisting of dopamine, dopa Lt; / RTI > Thus, in the complex according to the present invention, dopamine, dopa (DOPA), or a mixture thereof may be used.

The complex is formed by linking the amine group of the chitosan to the para position of the catechol or catechol derivative by electrophilic aromatic substitution reaction, and the diol of the catechol or catechol derivative forms a bridge bond with the hydroxyapatite can do.

The composite exhibits different mechanical strengths depending on the content of hydroxyapatite, and hydroxyapatite shows an increase in maximum tensile strength in the range of 25 to 75% by weight based on the weight of the composite, and a maximum Tensile strength is shown, which is the most similar to the maximum tensile strength of human bone. Therefore, the content of hydroxyapatite in the composite may be suitably adjusted according to the object of the invention. For example, the content of hydroxyapatite is 25 to 75% by weight, 25 to 70% by weight, 30 to 75% by weight, 30 to 70% by weight or 40 to 60% by weight.

Depending on the content of chitosan, chitin, or mixtures thereof in the complex, the complex exhibits different strengths while maintaining bioavailability The content of chitosan, chitin, or a mixture thereof in the complex can be appropriately controlled in order to maintain high strength while maintaining bioavailability. For example, the content of the chitosan, chitin, or a mixture thereof may be 30-70 wt%, or 40-60 wt%, based on the weight of the composite. Also, in order to achieve the technical effect of the strength enhancement as described above, the mixing ratio of hydroxyapatite to chitosan, chitin, or a mixture thereof may be 1: 3 to 3: 1.

Depending on the content of catechol or catechol derivatives in the complex, the complex exhibits different strengths while maintaining bioavailability The content of catechol or catechol derivatives in the complex can be suitably controlled to maintain high bioavailability while maintaining bioavailability. The ratio of the content of the at least one catechol or catechol derivative selected from the group consisting of catechol, dopamine, dopa and methylcatechol is from 5 to 15 wt%, or from 7 to 15 wt%, based on the weight of the chitosan, chitin, 12% < / RTI > by weight.

The composite may advantageously have suitable mechanical strength to be useful as an organic reinforcing material composition and the composite according to the present invention has a modulus of elasticity in the dry state of from about 0.5 to 3.5 Gpa, from 0.7 to 3 Gpa, from 1 to 3, To 3 Gpa, or from 1.2 to 1.83 Gpa, and / or the modulus of elasticity in the wet state (saturation) may be on the order of 10 to 100 Mpa. Also, to obtain the desired tensile strength, the composite may have a moisture absorption rate in the saturated state of 180% or less, 100% or less, 90% or less, 80% or less, 70% or less, or 60% or less of the composite. Further, in order to obtain the desired effect in the living body, the complex may have an aspect ratio (ratio of long axis to short axis) of about 1 to 10, 2 to 8, or 3 to 6.

Another embodiment provides an organic reinforcing material composition comprising the composite. The organic reinforcing material composition may be in the form of a film, a filament, a nonwoven fabric, or the like, but is not limited thereto and may be any material composition requiring strength.

Another embodiment provides a product made from an organic reinforcing material composition comprising the composite. The product may be any reinforcing material product that requires strength, including biomaterials applied to the living body.

The reinforcing material product may be any of a variety of materials such as artificial ligaments, artificial tendons, artificial dental materials (e.g. artificial Sharpey's fiber, artificial periodontal ligament), artificial skin, surgical suture, artificial dialysis membrane, Therapeutic aids, garment fibers, tire cords (durability and running characteristics of tires, reinforcement of fiber-reinforced materials inside the rubber to improve stability), and the like.

Another embodiment provides a method of making the composite. More specifically, the method comprises: adding hydroxyapatite to chitosan, chitin, or a mixture thereof dissolved in water, an ionic solvent, or a mixture thereof; And adding at least one catechol or catechol derivative selected from the group consisting of catechol, dopamine, dopa (DOPA), and methyl catechol dissolved in water, an ionic solvent or a mixture thereof to the resultant after the mixing step Step < / RTI >

The ionic solvent means any ionic liquid capable of dissolving chitosan, chitin, catechol or catechol derivatives. Examples of the ionic liquid include acetic acid or acetic acid aqueous solution, dimethylacetamide (DMAc) / LiCl (DMF) )), Ethylmethylimidazolium acetate and the like, and specifically may be an aqueous solution of 0.1 to 5M of acetic acid.

Hydroxyapatite; Chitosan, chitin, or a mixture thereof; And the contents of catechol or catechol derivatives are as described above. For example, the content of hydroxyapatite may be 25 to 75% by weight, 25 to 70% by weight, 30 to 75% by weight, 30 to 70% by weight or 40 to 60% by weight based on the weight of the composite. Also, the content of the chitosan, chitin, or a mixture thereof may be 30 to 70% by weight or 40 to 60% by weight based on the weight of the composite. Also, the ratio of the content of the at least one catechol or catechol derivative selected from the group consisting of catechol, dopamine, dopa and methylcatechol can be in the range of 5 to 15% by weight, based on the weight of the chitosan, chitin, have.

The complex provided by the present invention is a material to which catechol or catechol derivatives are added and is harmless to the human body and exhibits a strong mechanical strength and can be used as a variety of biomaterials such as artificial tendons, artificial ligaments, artificial dental materials, But the present invention is not limited thereto.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view of a method for producing a composite according to Example 1. Fig.
2A to 2C are photographs of a surface SEM measurement of the synthesized film according to Example 1, wherein FIG. 2A shows a synthesized # HA25 film surface, FIG. 2B shows a synthesized # HA50 film surface, Film surface.
3 is a cross-sectional SEM measurement photograph of the synthesized film according to Example 1. Fig.
4A is a cross-section of the synthesized # HA50 film according to Example 1, and FIG. 4B is a cross-sectional view of a synthesized 50% HA film according to Comparative Example 2. FIG. Lt; / RTI >
Shows the apaptide ¹ is phosphate mode ^- Figure 5 shows an FTIR analysis 3500cm according to Example ^5-1 shows an ^{OH peak, 1020 cm -1, 600} cm -1, 562 cm.
6 is a graph showing the tensile strength of the composite according to Example 6. Fig.
7 is a graph showing the hygroscopicity of the composite according to Example 7. Fig.
FIG. 8 is a graph showing the cell viability of the osteoblast according to Example 8. The white circle indicates the result of the complex # HA50 (50% HA + Dopamine) of Example 1, , And the black inverted triangle (▼) shows the result of the composite (50% HA) of Comparative Example 2.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

[ Example ]

Example  One. Hydroxyapatite / Chitosan / dopamine complex preparation

The complexes were prepared as shown in Fig. Specifically, an aqueous calcium hydroxide solution (96% pure and maximum 3 wt% CaCO ₂ ) was added to the reaction vessel and heated to 98 ° C constantly. While heating, an aqueous solution of orthophosphoric acid (85% orthophosphoric acid, H ₃ PO ₄ ) was added at 2 mL / min. When the pH of the solution in the reaction vessel became 8.01 (t1), a solution of chitosan dissolved in a 1% (v / v) acetic acid aqueous solution at a concentration of 10 g / L was added to the reaction vessel. When the pH in the reaction vessel reached 6, a solution of 1 g / L of dopamine dissolved in a 1% (v / v) acetic acid aqueous solution was added to the reaction vessel and stirred for 30 minutes with a stirrer.

 The amount of the compound to be added including the aqueous solution of calcium hydroxide and the aqueous solution of orthophosphoric acid is shown in Table 1 below, and dopamine was added in an amount of 10% (w / w) of chitosan added.

Sample name Mixing amount Hydroxyapatite
(wt%) Ca (OH) ₂
(mmol) H ₃ PO ₄
(mmol) Chitosan solution
(mL) Dopamine
Solution
(mL) # HA25 3 1.8 90 90 25 # HA50 10 6 90 90 50 # HA75 21 12.6 90 90 75

Thereafter, the temperature inside the reaction vessel was lowered to room temperature, and each of # HA25, # HA50, and # HA75 in the reaction vessel was transferred to a petri dish (using a separate Petri dish for each sample) And each sample was allowed to dry for one day while maintaining the temperature at 37 ° C. Each dried sample was treated with sodium hydroxide (NaOH) for 30 minutes to complete each film, and each of the films was immersed in water and ethanol to remove sodium hydroxide remaining on the film. Then, each film made in the Petri dish was taken out, and the shape of molecules constituting the film was observed through a scanning electron microscope (SEM) (JEOL electron microscope). The results are shown in FIGS. 2A, 2B and 2C.

2A is a SEM photograph of the synthesized # HA25 film surface, FIG. 2B is a SEM measurement photograph of the synthesized # HA50 film surface, and FIG. 2C is an SEM measurement photograph of the synthesized # HA75 film surface Lt; / RTI >

The cross section of the synthesized # HA50 film was observed through SEM (JEOL electron microscope), and the result is shown in FIG.

FIG. 3 shows SEM measurement photographs of the synthesized # HA50 film cross section, showing that the nanostructure is evenly distributed throughout the film.

The cross section of the synthesized # HA50 film was observed through TEM, and the result is shown in Figure 4a.

FIG. 4A is a TEM photograph of the synthesized # HA50 film, showing that needle-like nanostructure is formed on the film and the aspect ratio is increased

Example  2. Hydroxyapatite / Chitosan / Waveguide  Composite manufacturing

A film was prepared in the same manner as in Example 1 except that dopa (DOPA) was used in place of dopamine in the production method of # HA50.

The surface and cross section of the film were observed through SEM in the same manner as in Example 1, and the cross section of the film was observed through TEM. As a result, it was confirmed that the aspect ratio was increased.

Example  3. Hydroxyapatite / Chitosan / Methylcatechol  Composite manufacturing

A film was prepared in the same manner as in Example 1 except that methyl catechol was used in place of dopamine in the production method of # HA50.

The surface and cross section of the film were observed by SEM in the same manner as in Example 1, and the cross section of the film was also confirmed by TEM.

Example  4. Hydroxyapatite / Chitosan / catechol complex preparation

A film was prepared in the same manner as in Example 1 except that catechol was used in place of dopamine in the production method of # HA50.

The surface and cross section of the film were observed by SEM in the same manner as in Example 1, and the cross section of the film was also confirmed by TEM.

Comparative Example  1. Production of chitosan complex

(High molecular weight, Sigma-aldrich, Chitosan 419419- (Coarse ground flakes and powder) 800-2000 cP, 1% in 1% acetic acid, Brookfield ( lit.) and DDA (80% or more) were melted and dissolved under ultrasound at 40 ° C for 24 hours to prepare an aqueous acetic acid solution in which chitosan was dissolved. 30 ml of an aqueous acetic acid solution in which the chitosan was dissolved was placed in a Petri dish coated with a Teflon tape as a whole. The petri dish was dried in a convection oven at 40 캜 for 2 days to produce a freestanding 100% film of about 0.1 mm.

Comparative Example  2. Hydroxyapatite / Chitosan complex preparation

25 wt%, 50 wt%, 75 wt% hydroxyapatite / chitosan film was prepared in the same manner as in Example 1 except that dopamine was not added in the production process of # HA25, # HA50, and # HA75. Samples of the hydroxyapatite / chitosan film without dopamine thus prepared were designated as 25% HA, 50% HA, and 75% HA, respectively. The content of each component contained in the sample is shown in Table 2 Respectively.

Sample name Mixing amount Hydroxyapatite
(wt%) Ca (OH) ₂
(mmol) H ₃ PO ₄
(mmol) Chitosan solution
(mL) 25% HA 3 1.8 90 25 50% HA 10 6 90 50 75% HA 21 12.6 90 75

The cross-section of the prepared film was observed through TEM as in Example 1, and the result for 50% HA was shown in FIG. 4B.

4B is a TEM photograph of the cross section of the 50 wt% hydroxyapatite / chitosan film (50% HA).

In comparison between FIG. 4B and FIG. 4A, the photograph shown in FIG. 4A shows that a needle-shaped nanostructure is formed on the film and the aspect ratio is relatively increased.

Example  5. FTIR  analysis

Each of the films prepared in Example 1 was scanned at 4000-400 / cm 2 in an attenuated total reflection (ATR) mode using a BIORAD-excalibur series at a resolution of 2 / cm, and the FTIR analysis was performed. Respectively.

Figure 5 shows an FTIR analysis 3500cm ^{- 1} denotes the ^{OH peak, 1020 cm -1, 600} cm -1, 562 cm - would showing a apaptide the ^first mode is a phosphate, a black # HA25 of Figure 5, red Means # HA50, and blue means # HA75.

As shown in Fig. 5, it was confirmed that the film had distinct peaks of hydroxyapatite, which means that a complex containing hydroxyapatite was successfully prepared.

Example  6. The tensile strength  Test

The 100 wt% hydroxyapatite film was too brittle to fail the tensile strength test, and 75 wt% hydroxyapatite / chitosan / dopamine film samples also tended to be somewhat crumbly. The film of # HA25 and # HA50 prepared in Example 1, the 25% HA film and the 50% HA film prepared in Comparative Example 2 were cut into a rectangular shape of 1 cm x 3 cm and the thickness was cut to 0.001 mm by using a micrometer Respectively. In the case of dry, it refers to a film dried in a vacuum oven for 3 hours or more. In the case of wet, it means a sample saturated by immersing in 0.15M PBS for 5 hours.

 Using a tensile strength testing apparatus (Instron 3340 model), the strain rate was set at 0.5 mm / min in the young's constant extension rate mode, and the distance between the specimen clamp and the clamp was set at 1 cm. The obtained results are shown in Tables 2 and 6 Respectively.

Table 3 shows the elastic modulus (E), the ultimate tensile strength (UTS) and the elongation (ETS) of the films, and FIG. 6 shows the results of the tensile strength test .

6, stress is a value obtained by dividing the pulling force by F (force) / A (area) by the cross-sectional area, and the unit is N / m ² . elongation means the increased ratio [(final length - initial length) / initial length] x100 . Thus, the initial length and area are substituted into the maximum tensile strength testing instrument and actuated to obtain a value. The graph shows that the X-axis is the elongation and the Y-axis is the stress. The value obtained by multiplying the initial slope before the inflection point by 100 is called young's modulus. The point at which the inflection point occurs is called the yield point. The stress at this time is called yield stress. The breaking point is called the breaking point, and the strain at this time is the breaking strain, and the stress at this time is called the breaking stress. The maximum strain at break is called the maximum tensile strength.

Sample name Elastic modulus (Mpa) Maximum Tensile Strength (Mpa) extension(%) 25% HA (dry) 1744.00437.96 34.00 3 25% HA (wet) 30.03 5.81 21 # HA25 (25% Ha + Dopamine (dry)) 1469.03 24.72 4 # HA25 (25% Ha + Dopamine (wet)) 39.23 3.22 12 50% HA (dry) 2259.00 39.58 11 50% HA (wet) 28.88 4.81 9 # HA50 (50% Ha + Dopamine (dry)) 2613.80 30.02 4 # HA50 (50% Ha + Dopamine (wet)) 47.70 4.55 11

As shown in Table 3 and FIG. 6, the film of # HA50 prepared in Example 1 exhibited a relatively high modulus of elasticity and a maximum tensile strength, as well as a low elongation, as compared with the 50% HA film of Comparative Example 2.

The elastic modulus of the film of # HA50 prepared in Example 1 showed about 2 Gpa, which is weaker than that of human bone (12-18 Gpa), but it is affected by periodontal, ligament-like bones And interstitial tissue between the tough tissue (1.2-1.8 Gpa).

Example  7. Hydroxyapatite / Chitosan / catechol complex Moisture absorption rate  Test

The equilibrium water content (EWC) of the hydroxyapatite / chitosan / catechol complex prepared in Example 4 was measured. The moisture absorption rate of the sample was measured as follows.

The weight (W ₀ ) of the completely dried sample was measured and then immersed in 0.15 M phosphate buffered saline (pH 7.4) for 5 hours, and the weight (Wt) was measured. The weight was measured with a precision balance having a minimum unit of 0.0001. The moisture absorption rate (%) was defined as 100 X (W _t -W ₀ ) / W _t .

As a result of previous studies, the hygroscopic rate of pure chitosan was about 66% (Biotechnology Progress, 2013, 29, 505-512) and about 160-180% for hydroxyapatite / chitosan complex, / Chitosan / catechol complex was about 50%. This indicates that the water resistance of the hydroxyapatite / chitosan / catechol complex is significantly improved compared to the chitosan and hydroxyapatite / chitosan complexes.

Example  8. Hydroxyapatite / Chitosan / catechol complex Osteoblast  Experiment

The cell activity of the hydroxyapatite / chitosan / catechol complex prepared in Example 4 was measured as follows.

Specifically, rat osteoblast (MC3T3-E1; Riken cell bank) was used with an animal cell culture medium (alpha-MEM; Hyclone) containing 10% FBS (bovine serum) and 1% antibiotic-antimycotic And cultured in a 37 ° C incubator.

The cells were detached from the cell culture dish and diluted to 2x10 ⁵ cells / ml in an alpha-MEM (Hyclone; FBS-free) containing 1% antibiotic-antimycotic (Hyclone) The complex film of Example 4 (hydroxyapatite / chitosan / catechol complex) was cut into a dish (Falcon, USA) to fit the size of the culture dish. The cells were then injected in an amount of 1 × 10 ⁵ / Incubated in an incubator and quantified live cells every 24 hours. To quantify living cells, 50 μl of a cell counting kit-8 (Dojindo, Japan) solution was injected into the wells and further cultured for 3 hours. The following assay was performed.

Living cells are found in the mitochondria in which the water-soluble form of 2- (2-methoxy-4-nitrophenyl) -3- (4-nitrophenyl) -5- (2,4- disulfophenyl) -2H-tetrazolium (WST- formazan), so the absorbance at 450 nm was measured through a spectrophotometer to measure the amount of formazan dissolved in the medium.

In order to continue culturing, the cells were washed with PBS, and 1 ml of alpha-MEM (Hyclone) containing 10% fetal bovine serum (HClone) and 1% antibiotic-antimycotic (Hyclone) Lt; / RTI > The relative extinction coefficient at 450 nm of CCK medium means the relative viable cell number on a specific surface. The relative extinction coefficient according to the incubation time was measured while culturing for 3 days, and the number of viable cells relative to that at the time of adhesion was shown in Fig.

Cell activity was measured by the same method except that the complex of Comparative Example 2 was used in place of the complex of Example 4 in the measurement method, and is shown in Fig. The white circle is the result of the complex # HA50 (50% HA + Dopamine) of Example 1, and the black inverted triangle is the result of the composite 50% HA of Comparative Example 2. [ As shown in Fig. 8, the number of surviving osteoblasts on the complex of Example 4 was about 20% smaller than the number of osteoblasts on the complex of Comparative Example 2. [ However, the addition of dopamine or catechol compounds does not increase cytotoxicity, since the difference is not large and is slow but draws the growth curve.

Example  9. Hydroxyapatite / Chitosan / catechol complex aspect ratio  Measure

The aspect ratios of the hydroxyapatite / chitosan complex of Comparative Example 2 and the hydroxyapatite / chitosan / catechol complex of Example 4 were analyzed by ImageJ program (US NIH National Institutes of Health) Respectively.

The addition of Dopamine resulted in an increase in aspect ratios, and at 25% there was little increase in aspect ratio.

Sample name Aspect ratio 50% HA 2.48 # HA50 4.44 75% HA 2.50 # HA75 5.71

Table 4 shows the Aspect Ratio. As shown in Table 4, HA in the body has a high aspect ratio and can be considered to have an aspect ratio of about 3 to 6. The aspect ratios of the 50% HA and 75% HA prepared in Comparative Example 2 were less than 3, but the # HA50 and # HA75 films prepared in Example 1 showed an aspect ratio of 4.44 and 5.71, respectively.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.

Claims (14)

Hydroxyapatite;
Chitosan, chitin, or a mixture thereof; And
At least one catechol derivative selected from the group consisting of catechol, dopamine, dopa (DOPA) and methyl catechol,
Wherein the amine group of the chitosan, chitin, or mixture thereof is bound to the para position of the catechol derivative,
The diol of the catechol derivative is crosslinked to the hydroxyapatite,
The content of hydroxyapatite is 25 to 75 wt% based on the weight of the composite,
The dry state modulus of the composite is 0.5 to 3.5 Gpa,
Complex. delete The method according to claim 1,
Wherein the content of the chitosan, chitin, or mixture thereof is 30 to 70 wt%, based on the weight of the composite. The method according to claim 1,
Wherein the catechol derivative is dopamine, dopa, or a mixture thereof. The method according to claim 1,
Wherein the content ratio of the catechol derivative is 5 to 15% by weight, based on the weight of the chitosan, chitin, or mixture thereof. 6. An organic reinforcing material composition comprising the composite of any one of claims 1 and 5. The organic reinforcing material composition of claim 6, wherein the composition is in the form of a film, a filament, or a nonwoven. A product made from an organic reinforcing material composition comprising the composite of any one of claims 1 and 5 to 5. 9. The method of claim 8, wherein the article is at least one selected from the group consisting of artificial ligament, artificial tendon, artificial dental material, artificial skin, surgical suture, artificial dialysis membrane, Products. (a) adding and mixing chitosan, chitin, or a mixture thereof dissolved in water, an ionic solvent or a mixture thereof to a mixture of an aqueous solution of calcium hydroxide and an aqueous solution of phosphoric acid;
(b) adding at least one catechol derivative selected from the group consisting of catechol, dopamine, dopa (DOPA), and methyl catechol dissolved in water, an ionic solvent or a mixture thereof to the resultant product after the mixing step ; And
(c) adding hydroxyapatite,
Wherein the amine group of the chitosan, chitin, or mixture thereof is bound to the para position of the catechol derivative,
The diol of the catechol derivative is crosslinked to the hydroxyapatite,
Wherein the hydroxyapatite content is 25 to 75 wt% based on the weight of the composite,
The dry state modulus of the composite is 0.5 to 3.5 Gpa,
≪ / RTI > The method for producing a composite according to claim 10, wherein the steps (a) and (b) are performed under heating conditions, and the step (c) is performed at room temperature. 11. The method of claim 10, wherein the content of the chitosan, chitin, or a mixture thereof is 30-70 wt% based on the weight of the composite. 11. The method of claim 10, wherein the catechol derivative is dopamine, dopa, or a mixture thereof. 11. The composition of claim 10, wherein the ratio of at least one selected from the group consisting of catechol, dopamine, dopa (DOPA) and methylcatechol is from 5 to 15% by weight, based on the weight of the chitosan, chitin, Gt;

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