KR20170090358A - Organic-inorganic hybrid micro particles and use therof - Google Patents

Abstract

The present invention discloses oil-inorganic hybrid microparticles and uses thereof. The oil-inorganic hybrid microparticle according to an embodiment of the present invention may include a surface-modified hydroxyapatite; And an organic polymer layer laminated on the surface of the surface modified hydroxyapatite. The oil-inorganic hybrid microparticles according to an embodiment of the present invention may be contained as an active ingredient of a regenerative medicine for periodontal tissue or surrounding tissue of the implant.

Description

ORGANIC-INORGANIC HYBRID MICRO PARTICLES AND USE THEROF <br> <br> <br> Patents - stay tuned to the technology ORGANIC-INORGANIC HYBRID MICRO PARTICLES AND USE THEROF

The present invention relates to oil-inorganic hybrid microparticles and uses thereof.

The loss of the teeth not only impairs the masticatory function, but also progressively absorbs the alveolar bone and gums, making it difficult to implant and reconstruct the prosthesis. When the alveolar bone is destroyed or absorbed by inflammation, trauma, neoplasm, etc., it is almost impossible to regenerate the original shape unlike the bone existing in other parts of the body.

In order to recover this, it is necessary to evaluate the absorbed ridge and the osteocyst. If it is difficult to regenerate bone, use bone graft material with excellent bone forming ability, or mix autogenous bone. If it is judged that bone regeneration is relatively easy Non-autogenous bone graft material with bone conduction capability may also be transplanted.

In addition to the evaluation of the graft site, patients have different bone healing ability. Therefore, if there are systemic conditions or diseases that interfere with the elderly or osseous healing, avoid bone grafting, and be careful in selecting bone graft materials and surgical methods.

In recent studies, it has been reported that when autogenous bone is mixed with heterogeneous bone, the rate of autogenous bone is higher, new bone formation is not induced. Therefore, autogenous bone is rapidly changing into substitute implant in clinical area.

The ideal bone graft material is easy to obtain, it shows bone conduction and bone-inducing ability without rejection in vivo, and after bone formation, bone graft material should be absorbed and replaced with original bone tissue which can respond to various physiological functions around bone. In fact, there is no such bone graft material.

Since bone tissue is hard tissue but it plays an important role in maintaining the homeostasis of the body in response to the surrounding environment through continuous modification, it is necessary to use bone graft materials to make the bone structure simple, Development is continuing.

To this end, there are various tissue engineering efforts to analyze bone and organic materials and minerals to devise a bone graft material or to apply a signal transducing material that directly induces bone formation.

At present, the most active mineral characterization is hydroxyapatite, which is an important mineral component of tooth and bone, and it is used as a main component of many bone graft materials.

 Although hydroxyapatite has the highest crystallinity among calcium phosphate compounds, it is degraded at a slow rate, but it is known to exhibit the most excellent bone regeneration effect among various bone graft materials because it is a substance existing in vivo and has high biocompatibility.

Bone graft materials are classified into synthetic bone, allogeneic bone, heterogeneous bone, and autogenous bone according to their origins. Since most of the synthetic bone and heterogeneous bone are composed of hydroxyapatite as a main component and the size and microstructure of the graft material are different, Several ingredients are used together.

Particularly, hydroxyapatite is not easily absorbed in vivo or may not exist as a filler in some graft materials. Therefore, hydroxyapatite may be used as a filler to change the structure, composition, crystal form and the like in order to control the absorption rate and induce new bone. Processing methods are being studied.

In the case of synthetic bone, calcium hydroxide is added to control the rate of absorption of hydroxyapatite, or a process for imparting bone structure and porous structure observed in bone structure is added. Even if bone graft materials are of the same origin, if the bone graft material is fired at a different temperature or an additional process is added, the bone grafting ability and response of the graft material are completely different, and the regeneration ability of the bone graft material may be changed.

The high temperature treatment of the heterogeneous bone was first designed to remove the protein component of the antigen. The heat treatment at 300 ° C removes the organic component of the heterogeneous bone and maintains the ratio and structure of the inorganic component originally possessed by the bone . However, treatment of graft material at higher temperature can easily remove organic matter, but calcination temperature and calcination time are key because changes in the ratio of calcium and phosphorus in the bone itself and changes in structure may occur.

Another effort is to modify the surface morphology of grafts to promote attachment of bone-related cells. Increasing surface roughness (roughness) with acids is commonly used in implants. Surface roughness is affected by acid type, concentration, temperature and time. In general, too strong an acid treatment weakens the strength of the bone, and acidic substances remain on the surface, which can have a negative impact on tissue regeneration.

On the other hand, Korean Patent No. 10-1472745, which is a prior patent of the present inventors, discloses a bioadhesive containing surface-modified hydroxyapatite and the above-mentioned surface-modified hydroxyapatite as an active ingredient. However, Korean Patent No. 10-1472745 only discloses a surface modified hydroxyapatite and a bioadhesive containing the hydroxyapatite as an active ingredient, and does not disclose the application materials of surface modified hydroxyapatite and uses thereof.

Accordingly, there is a need for research and development of a bioregistration therapeutic agent using a hydroxyapatite-based material having improved effects over conventional hydroxyapatite-based materials.

Korean Patent No. 10-1472745 (Apr. 201, 2019) "Bio-adhesive containing surface-modified hydroxyapatite and use thereof"

An embodiment of the present invention relates to a use of an oil-inorganic hybrid microparticle comprising a surface-modified hydroxyapatite and an organic polymer layer laminated on the surface of the surface-modified hydroxyapatite as a regenerative treatment agent for periodontal tissue or implant- .

The oil-inorganic hybrid microparticle according to an embodiment of the present invention may include a surface-modified hydroxyapatite; And an organic polymer layer laminated on the surface of the surface modified hydroxyapatite.

The surface-modified hydroxyapatite is modified through a linking compound covalently bonded to the surface of hydroxyapatite, the linking compound is a compound represented by BC, and the B is trimethoxy, triethoxy ( triethoxy or halogen, and C may be an aldehyde, an isocyanate, an epoxy or a glycidoxy.

The organic polymer layer may be selected from the group consisting of collagen, hyaluronic acid, chondroitin sulfate, alginate, chitosan, poly-L-lysine, RGD peptide (RGD peptide), a block copolymer micelle, and a graphene.

The organic polymer layer may further include an antibiotic or a growth factor.

The antibiotic may include any one selected from the group consisting of chlorohexidine, tetracycline, minocycline, doxycycline, and arrestin.

The growth factor may include any one selected from the group consisting of BMP2, FGF2, VEGF, TGF? And Substance P.

The organic polymer layer may be laminated in the order of a first organic polymer layer, a second organic polymer layer, and a third organic polymer layer, and the third organic polymer layer may be an antibiotic.

The regenerative medicine for periodontal tissue or tissue around the implant according to the embodiment of the present invention contains the oil-inorganic hybrid microparticles as an active ingredient.

The oil-inorganic hybrid microparticles according to an embodiment of the present invention include a compound represented by the following formula (1).

&Lt; Formula 1 >

A-X-YZ

(Wherein A is hydroxyapatite, X is a compound represented by BC, B is trimethoxy, triethoxy, or halogen, and C is an aldehyde aldehyde, isocyanate, epoxy or glycidoxy, Y is collagen, hyaluronic acid, chondroitin sulfate, alginate, chitosan, Chitosan, Poly-L-Lysine, RGD peptide, Block copolymer micelle or Graphene, Z is D or E, Chlorohexidine, tetracycline, minocycline, doxycycline or arrestin, and E is BMP2, FGF2, VEGF, TGF [beta] or Substance P.

The oil-inorganic hybrid microparticles may be in powder form.

The regenerative medicine for periodontal tissue or tissue around the implant according to the embodiment of the present invention contains the oil-inorganic hybrid microparticles as an active ingredient.

The oil-inorganic hybrid microparticles comprising the surface-modified hydroxyapatite according to the embodiment of the present invention and the organic polymer layer laminated on the surface of the surface-modified hydroxyapatite are effective for the regenerative treatment agent of the periodontal tissue or the tissue around the implant And can effectively prevent or treat periodontitis or peri-implantitis.

In addition, in the embodiment of the present invention, the oil-inorganic hybrid microparticles can completely fill the bone defect region even when the bone defect site is small, narrow, and irregular in shape.

FIGS. 1A and 1B illustrate a hybrid microparticle according to an embodiment of the present invention.
FIG. 2 is a view showing an oil-inorganic hybrid microparticle according to an embodiment of the present invention.
FIG. 3 shows the use of a regenerative therapeutic agent for surrounding tissues of an implant containing organic-inorganic hybrid microparticles as an active ingredient according to an embodiment of the present invention.
FIG. 4 shows the results of confirming the pellet-forming ability of the oil-inorganic hybrid microparticles according to an embodiment of the present invention.
FIG. 5 shows whether a hybrid material formed by mixing collagen and conventional hydroxyapatite in the same ratio as the oil-inorganic hybrid microparticles according to an embodiment of the present invention maintains the pellet shape.

In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may unnecessarily obscure the subject matter of the present invention. In addition, the terms described below are established in consideration of the functions of the present invention, and these may vary depending on the intention of the manufacturer or custom in the industry, and the definition should be based on the contents throughout the specification.

An embodiment of the present invention relates to an organic-inorganic hybrid microparticle and a use thereof, and more particularly, to an organic-inorganic hybrid microparticle and a use thereof, Inorganic hybrid microparticles and the oil-inorganic hybrid microparticles as an active ingredient.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to the accompanying drawings.

FIGS. 1A and 1B illustrate a hybrid microparticle according to an embodiment of the present invention.

1B is a cross-sectional view showing a state in which the organic-inorganic hybrid microparticles are cut in the X-X 'direction in FIG. 1A; FIG. 1A is a perspective view showing the organic-inorganic hybrid microparticles according to the embodiment of the present invention; to be.

Referring to FIGS. 1A and 1B, a U-inorganic hybrid microparticle 100 according to an embodiment of the present invention includes a surface-modified hydroxyapatite 110; And an organic polymer layer 120 laminated on the surface of the surface modified hydroxyapatite 110.

The surface-modified hydroxyapatite (110) may be formed by modifying a surface-modified hydroxyapatite with a linking compound covalently bonded to the surface of hydroxyapatite. Specifically, the surface-modified hydroxyapatite 110 can be formed by modifying the surface of the hydroxyapatite by connecting a linking compound to the surface of the hydroxyapatite through a covalent bond.

The linking compound may be, for example, a compound represented by BC. B is a moiety which binds to hydroxyapatite, for example, trimethoxy, triethoxy, or halogen. C is a moiety opposite to B, Refers to a portion separated from a portion bonding with hydroxy and may be composed of, for example, aldehyde, isocyanate, epoxy, or glycidoxy.

Here, since hydroxyapatite itself has a bone-forming ability, hydroxyapatite can be used for local regeneration of bone at the site where cartilage or tissue is adhered when hydroxyapatite is applied between bone and cartilage or bone and tissue Thereby achieving a better bone-cartilage or bone-tissue adhesion effect.

In addition, the surface modified hydroxyapatite (110) is modified by the surface of the hydroxyapatite through a linking compound, so that it is not interrupted between the structures bonded to pure hydroxyapatite, and can exhibit a connective adhesive effect.

The organic polymer layer 120 is formed on the surface of the surface modified hydroxyapatite 110. Specifically, the organic polymer layer 120 is formed on the surface of the surface-modified hydroxyapatite 110 to form the organic-inorganic hybrid microparticle 100.

Inorganic microparticles without the organic polymer layer 120 can stay on the surface of the tissue by electrostatic interaction only when the surface charge is complementary to the surrounding tissue. However, most inorganic microparticles do not have charge balance balance), the interaction with surrounding tissues is weakened.

Inorganic microparticles having no organic polymer layer 120 can not be bound to each other due to interaction between inorganic microparticles, and thus tend to disperse and disappear according to the flow of fluid rather than fill the volume while being stably present in the bone defect. .

On the other hand, in the case of the organic-inorganic hybrid microparticle (100) having the organic polymer layer (120) which is biocompatible on the inorganic microparticle surface, the particles stably exist on the biological tissue surface through the interaction between the organic polymer and the biomaterial Inorganic hybrid microparticle 100 can stably stay in a bone defect portion due to the interaction between particles and particles through the affinity between organic polymers.

The organic polymer layer 120 may be formed of, for example, collagen, hyaluronic acid, chondroitin sulfate, alginate, chitosan, poly-L-lysine -Lysine, an RGD peptide, a block copolymer micelle, and a Graphene.

In addition, the organic polymer layer 120 may include an antibiotic or a growth factor. In detail, the organic polymer layer 120 may be composed of an organic polymer and a compound containing an antibiotic or a growth factor.

For example, the organic polymer layer 120 may be composed of a compound containing an organic polymer and an antibiotic, or may be composed of a compound containing an organic polymer and a growth factor. 1A and 1B, the organic polymer layer 120 may be an organic polymer layer 120 containing an antibiotic or an organic polymer layer 120 including a growth factor.

When the organic polymer layer 120 contains an antibiotic in the interior of the organic polymer layer, the antibiotic may be selected from the group consisting of chlorohexidine, tetracycline, minocycline, doxycycline, and arrestin. &Lt; RTI ID = 0.0 &gt; and / or &lt; / RTI &gt;

Herein, antibiotics mean substances that kill or inhibit microorganisms (bacteria). For example, antibiotics may be used to remove germs present in tissues around the periodontal or implant.

When the organic polymer layer 120 includes a growth factor in the organic polymer layer, the growth factors include BMP2 (bone morphogenetic protein 2), FGF2 (fibroblast growth factor 2), VEGF (vascular endothelial growth factor) (Transforming Growth Factor Beta) and Substance P (P substance).

Herein, a growth factor means a polypeptide promoting various cell division or growth and differentiation. For example, the growth factor may be a substance promoting growth of bone, fibroblast, or endothelial cell of tissue around periodontal or implant have.

As shown in FIGS. 1A and 1B, the organic-inorganic hybrid microparticle 100 according to the embodiment of the present invention is a structure in which an organic polymer layer 120 is laminated on the surface of a hydroxyapatite 110 Lt; / RTI &gt;

Here, 'lamination' does not mean that the surface of the hydroxyapatite 110 is formed on one surface of the surface-modified hydroxyapatite 110 but it is formed over the entire surface of the surface-modified hydroxyapatite 110.

For example, the organic polymer layer 120 may be formed by coating over the entire surface of the surface modified hydroxyapatite 110. In other words, the organic polymer layer 120 may be formed to surround the entire surface of the surface modified hydroxyapatite 110.

In addition, the organic-inorganic hybrid microparticle 100 according to the embodiment of the present invention may be in the form of a plate, as shown in FIG. 1A and FIG. 1B, but is not limited thereto. In particular, the organic-inorganic hybrid microparticles 100 may be in various forms such as a plate type, a sphere type, and a rod type.

In addition, the organic-inorganic hybrid microparticle 100 according to the embodiment of the present invention is characterized by having a micro-level size. For example, the organic-inorganic hybrid microparticles 100 may be from 10 탆 to 500 탆, preferably from 20 탆 to 300 탆, and more preferably from 50 탆 to 150 탆.

FIG. 2 is a view showing an oil-inorganic hybrid microparticle according to an embodiment of the present invention.

According to an embodiment of the present invention, the organic polymer layer 120 of the organic-inorganic hybrid microparticle 100 may be formed in multiple layers. In detail, the organic polymer layer 120 may be formed of any one layer selected from a first layer to a third layer.

FIG. 2 is a schematic view illustrating an organic polymer layer 120 formed of three layers of organic-inorganic hybrid microparticles 100 including an organic polymer layer 120 that can be formed in multiple layers according to an embodiment of the present invention. - inorganic hybrid microparticles (100).

2, the organic-inorganic hybrid microparticle 100 according to an embodiment of the present invention includes a surface modified hydroxyapatite 110 and an organic polymer layer 110 laminated on the surface of the surface modified hydroxyapatite 110, The organic polymer layer 120 is formed by stacking a first organic polymer layer 121, a second organic polymer layer 122 and a third organic polymer layer 123 in this order.

When the organic polymer layer 120 is formed in a multi-layered structure, the organic polymer layers may be formed of organic polymers having different functions so that different functions can be realized as one particle. Depending on the decomposition rate of the organic polymer, Each function can be implemented with a time difference.

For example, when the outer layer of the organic polymer layer 120 is formed of an organic polymer containing antibiotics and rapidly decomposed, and the inner layer is formed of an organic polymer containing a growth factor and slowly decomposing, And release the growth factor over time.

According to an embodiment of the present invention, the first organic polymer layer 121, the second organic polymer layer 122, and the third organic polymer layer 123 may include different antibiotics or growth factors, respectively.

For example, the first organic polymer layer 121 may have a structure regeneration such as BMP2 (Bone Morphogenetic Protein 2), FGF2 (Fibroblast Growth Factor 2), TGFβ (Transforming Growth Factor Beta) or Substance P And the second organic polymer layer 122 may be an organic polymer layer including an angiogenesis promoting factor such as VEGF (Vascular Endothelial Growth Factor), and the third organic polymer layer 122 may be an organic polymer layer including an angiogenesis promoting factor such as VEGF Layer 123 may be an organic polymer layer including, for example, antibiotics such as chlorohexidine, tetracycline, minocycline, doxycycline, and arrestin, But is not limited thereto.

In the organic-inorganic hybrid microparticle 100 according to one aspect of the present invention, the third organic polymer layer 123 of the organic polymer layer 120 may include an antibiotic.

If the organic polymer layer 123 containing antibiotics is present at the outermost periphery of the organic-inorganic hybrid microparticle 100, the killing effect of the bacteria due to the antibiotic can be obtained.

In addition, when an organic polymer layer 122 containing an angiogenesis promoting factor and / or an organic polymer layer 121 containing a tissue regeneration promoting factor are present inside the organic polymer layer 123 containing antibiotics, After bacterial killing, angiogenesis promoting factors and / or tissue regeneration promoting factors may facilitate the formation and / or regeneration of blood vessels and / or tissues.

On the other hand, when this is used as a regenerative treatment for periodontal tissue or surrounding tissues of the implant according to one aspect of the present invention, bacteria existing in periodontal tissues or tissues around the implant are killed through antibiotics, and then vascular growth promoting factors and / Regenerating or filling the periodontal tissue or surrounding tissue through growth factors such as promoters may effectively prevent or treat periodontitis or periplasmic periarthritis.

FIG. 3 shows the use of a regenerative therapeutic agent for surrounding tissues of an implant containing organic-inorganic hybrid microparticles as an active ingredient according to an embodiment of the present invention.

Referring to FIG. 3, it can be confirmed that the oil-inorganic hybrid microparticles 100 according to an embodiment of the present invention are filled between the implant and the surrounding tissue to regenerate the surrounding tissue of the implant.

The regenerative therapeutic agent for periodontal tissue or surrounding tissues according to an embodiment of the present invention contains oil-inorganic hybrid microparticles (100) as an active ingredient.

The organic-inorganic hybrid microparticle 100 includes a surface-modified hydroxyapatite 110 and an organic polymer layer 120 laminated on the surface of the surface-modified hydroxyapatite 110.

The hydroxyapatite constituting the surface-modified hydroxyapatite 110 is a substance mainly found in the teeth and bones of the body, and is a material for promoting the internal growth of the bone toward the filler or the implant in place of the cut bone. Is used.

 Accordingly, if the hydroxyapatite 110 is applied to the periodontal tissue or the tissue surrounding the implant, the hydroxyapatite itself may have bone formation ability in the periodontal tissue or the surrounding tissue of the implant.

On the other hand, the organic polymer layer 120 may include an antibiotic or a growth factor. Accordingly, after the periodontal tissue or the bacteria existing in the surrounding tissues of the implant are killed by the antibiotic or growth factor contained in the organic polymer layer 120, the periodontal tissue or surrounding tissue of the implant may be regenerated or buried, Peritonitis may be effectively prevented or treated.

In detail, the oil-inorganic hybrid microparticle 100 according to an embodiment of the present invention is contained as an active ingredient of a regenerative treatment agent for periodontal tissues or tissues surrounding an implant to effectively prevent or treat periodontitis or periplasmic periplasm.

In addition, since the size of the organic-inorganic hybrid microparticles 100 is micro level in the embodiment of the present invention, the bone defect site can be completely filled even if the bone defect site is small, narrow, and irregular in shape.

In one embodiment of the present invention, the organic-inorganic hybrid microparticle 100 includes an organic polymer layer 120 including a bioactive agent such as an antibiotic or a growth factor on the surface of a micro-sized hydroxyapatite 110 It is possible to secure a large surface area at which the bioactive factor can act.

Hereinafter, the organic-inorganic hybrid microparticles according to the embodiment of the present invention will be described in more detail with reference to the following description of the organic-inorganic hybrid microparticles according to the embodiment of the present invention .

The oil-inorganic hybrid microparticles according to an embodiment of the present invention include a compound represented by the following formula (1).

&Lt; Formula 1 >

A-X-YZ

In the formula (1), AX represents surface-modified hydroxyapatite (110), YZ represents a surface-modified hydroxyapatite (110) surface-coated with antibiotics or growth factors Organic polymer layer 120 &quot; Hereinafter, the formula 1 will be described in more detail.

In Formula 1, A-X means a linking compound for hydroxyapatite-surface modification.

In Formula 1, A is hydroxyapatite.

In Formula 1, X is a coupling compound for surface modification of hydroxyapatite (A), and may be a compound represented by BC.

B is a moiety binding to hydroxyapatite (A), may be trimethoxy, triethoxy or halogen, and C is a moiety which binds to hydroxyapatite (A) An aldehyde, an isocyanate, an epoxy, or a glycidoxy.

In the general formula (1), YZ is a compound containing Y and Z, which means an organic polymer layer laminated on the surface of the hydroxyapatite surface-modified and containing an antibiotic or a growth factor.

In Formula 1, Y is an organic polymer layered on the surface of hydroxyapatite (A) in a layer-by-layer manner, and includes collagen, hyaluronic acid, chondroitin sulfate Chondroitin sulfate, Alginate, Chitosan, Poly-L-Lysine, RGD peptide, Block copolymer micelle or Graphene .

In the above formula (1), Z may be D or E.

D may be an antibiotic, such as chlorohexidine, tetracycline, minocycline, doxycycline, or arrestin.

(EGF), BGF (Transforming Growth Factor Beta) and Substance P (P substance) as bone morphogenesis or regeneration-related growth factors, BMP2 (bone morphogenetic protein 2), FGF2 (Fibroblast Growth Factor 2) Lt; / RTI &gt;

Meanwhile, the oil-inorganic hybrid microparticles comprising the compound represented by Formula 1 according to an embodiment of the present invention may be in the form of a powder. For example, the oil-inorganic hybrid microparticle according to an embodiment of the present invention may be, for example, a powder having a micro-level size ranging from 10 μm to 500 μm.

The regenerative medicine for periodontal tissue or surrounding tissues according to the embodiment of the present invention contains oil-inorganic hybrid microparticles containing the compound represented by the formula (1) as an active ingredient.

In detail, the oil-inorganic hybrid microparticle according to the embodiment of the present invention is contained as an active ingredient of a regenerative treatment agent for periodontal tissue or surrounding tissue to effectively prevent or treat periodontitis or periplasmic periplasm.

Hereinafter, examples and comparative examples of the present invention will be described. The following examples are only illustrative of the present invention and the present invention is not limited to the following examples.

Example: Preparation of oil-and-inorganic hybrid microparticles

Hydroxyapatite A collagen molecule capable of forming a gel through self-assembly on the crystal surface is attached through covalent bonds and self-assembles between the collagen molecules to form pellets inorganic hybrid particles capable of forming micro-scale pellets.

Inorganic hybrid microparticles were formed in the following manner in order to confirm whether or not these organic-inorganic hybrid microparticles can actually form a gel and maintain its shape through self-assembly.

The microcrystals of hydroxyapatite and the type I collagen (type I collagen) thus surface-modified are immersed in distilled water, saline solution or PBS (50: 1 or 100: 1) in an aqueous solution of phosphate buffered saline and then reacted at room temperature for 30 minutes to form hydroxyapatite microcrystals whose surface was modified with type I collagen molecules. Respectively.

The hydroxyapatite to which the collagen molecules were adhered was dispersed in distilled water, saline solution or PBS solution, allowed to sink in the solution, and then the supernatant was discarded repeatedly.

The hydroxyapatite microcrystals whose surfaces were coated with an organic polymer matrix through the reaction were called oil-inorganic hybrid microparticles, and the oil-inorganic hybrid microparticles were dispersed in an aqueous solution at a low concentration and refrigerated.

In order to confirm the self-assembling property of the organic-inorganic hybrid microparticles, the organic-inorganic hybrid microparticles were placed in a container of the type in which they were to be formed, centrifuged and kept at a temperature of from room temperature to 37 ° C for at least 10 hours The pellet was taken out with a spatula so as not to be scattered, and placed in a 35 mm-diameter plastic dish and filled with PBS.

In the process of manufacturing the organic-inorganic hybrid microparticles, the reaction ratio between the collagen (organic) and the surface-modified hydroxyapatite (inorganic) was 1:50 or 1: 100, To determine the extent of the pellet scatter, the plastic plates containing the two samples were shaked 10 times each to assess the degree of pellet scatter (see FIG. 4).

FIG. 4 shows the results of confirming the pellet-forming ability of the oil-inorganic hybrid microparticles according to an embodiment of the present invention.

Referring to FIG. 4, the oil-inorganic hybrid microparticles formed at a ratio of 1:50 exhibited stable self-assembly, whereas the oil-inorganic hybrid microparticles formed at a ratio of 1: 100 showed more scattering of the pellets, As a result, it was confirmed that, at a ratio of 1: 100, the collagen molecules acting on the self-assembly of the organic-inorganic hybrid microparticles were relatively insufficient to maintain the shape of the pellet.

The organic - inorganic hybrid microparticles were able to form pellets by causing self - assembly between the collagen molecules while attaching collagen molecules through covalent bonds to the surface of the hydroxyapatite crystals.

The formation of pellets of organic-inorganic hybrid microparticles by self-assembly can completely fill the shape of the defect without specific three-dimensional morphogenesis according to the shape of the defect after implantation, And can be stably present in the form of

These three-dimensional pellets do not inhibit cell migration and tissue remodeling during tissue remodeling due to the micro-scale size of the particles and the nature of the organic-inorganic hybrid material, .

On the other hand, in order to confirm whether or not the pellets can be formed when the collagen molecules and the hydroxyapatite are mixed in the unmodified form, the hydroxyapatite crystals which have not undergone surface modification are used in an embodiment of the present invention Inorganic hybrid microparticles according to one embodiment of the present invention in the same ratio (1:50, 1: 100) forming the organic-inorganic hybrid microparticles according to one embodiment of the present invention and inducing the formation of pellets in the same manner as the oil- (See FIG. 5).

FIG. 5 is a graph showing the results of comparison between the pellet of a hybrid material formed by mixing collagen with a common hydroxyapatite (hydroxyapatite not surface-modified) at the same ratio as that of the oil-inorganic hybrid microparticles according to an embodiment of the present invention It is confirmed whether it maintains form.

5, when a general hydroxyapatite without surface modification is used, a mixture of collagen and hydroxyapatite is formed through simple mixing without forming organic-inorganic hybrid microparticles, whereby the ratio of collagen is relatively high Pellets were dispersed even when mixed at a high ratio of 1:50, and the shape of the pellet was maintained after shaking 10 times in contrast to the oil-inorganic hybrid microparticles according to an embodiment of the present invention I did.

In addition, the mixture mixed at a ratio of 1: 100 did not form the pellet shape, but the particles were dispersed. After 10 shaking, the particles were completely separated and dispersed evenly in the aqueous solution .

While the invention has been shown and described with reference to certain preferred embodiments thereof, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. This is possible. Therefore, the scope of the present invention should not be limited to the described embodiments, but should be determined by the equivalents of the claims, as well as the claims.

100: oil-inorganic hybrid microparticle
110: Surface modified hydroxy apatite
120: organic polymer layer
121: First organic polymer layer
122: second organic polymer layer
123: Third organic polymer layer

Claims (11)

Surface modified hydroxyapatite; And
The organic polymer layer laminated on the surface of the hydroxyapatite
Organic hybrid microparticles.
The method according to claim 1,
The surface-modified hydroxyapatite can be obtained by,
Modified via a linking compound covalently bonded to the surface of the hydroxyapatite,
The linking compound is a compound represented by BC,
Wherein B is trimethoxy, triethoxy or halogen,
Wherein said C is aldehyde, isocyanate, epoxy, or glycidoxy. 10. The oil-in-water hybrid microparticle of claim 1, wherein said C is aldehyde, isocyanate, epoxy or glycidoxy.
The method according to claim 1,
Wherein the organic polymer layer comprises:
A collagen, a hyaluronic acid, a chondroitin sulfate, an alginate, a chitosan, a poly-L-lysine, an RGD peptide, At least one selected from the group consisting of a block copolymer micelle and a graphene.
The method of claim 3,
Wherein the organic polymer layer comprises:
Inorganic hybrid microparticles characterized by further comprising an antibiotic or growth factor.
5. The method of claim 4,
The antibiotic,
Inorganic hybrid microparticles characterized by comprising any one selected from the group consisting of chlorohexidine, tetracycline, minocycline, doxycycline and arrestin. .
5. The method of claim 4,
The growth factor may be,
BMP2, FGF2, VEGF, TGF [beta] and Substance P, wherein the organic microparticle is selected from the group consisting of BMP2, FGF2, VEGF,
5. The method of claim 4,
Wherein the organic polymer layer comprises:
The first organic polymer layer, the second organic polymer layer, and the third organic polymer layer,
Inorganic hybrid microparticles, wherein the third organic polymer layer is an antibiotic.
An agent for regenerating periodontal tissue or surrounding tissue of an implant comprising the oil-inorganic hybrid microparticles according to any one of claims 1 to 7 as an active ingredient.
An organic-inorganic hybrid microparticle comprising a compound represented by the following formula (1).
&Lt; Formula 1 >
AX-YZ
(In the formula 1,
A is hydroxy apatite,
X is a compound represented by BC and B is trimethoxy, triethoxy or halogen, and C is an aldehyde, an isocyanate, an epoxy, Glycidoxy,
Y may be selected from the group consisting of collagen, hyaluronic acid, chondroitin sulfate, alginate, chitosan, poly-L-lysine, RGD peptide, Block copolymer micelle, or graphene,
Z is D or E and D is chlorohexidine, tetracycline, minocycline, doxycycline or arrestin, E is BMP2, FGF2, VEGF, TGFβ or Substance P).
10. The method of claim 9,
Inorganic hybrid microparticles,
Inorganic hybrid microparticles characterized by being in the form of a powder.
An agent for regenerating periodontal tissue or surrounding tissue of an implant comprising the oil-inorganic hybrid microparticles according to claim 9 or 10 as an active ingredient.

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