JP2012157628A - Shell granule or aggregate thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bone regeneration material which is excellent in bondability with surrounding tissues because of its granular shape, and has good bone reproducing ability even if the granule is broken.SOLUTION: The shell granule or the aggregate thereof is formed of a hard body which contains a hydraulic powder composition in its inside and has a shell obtained by hydration reaction of the powdery composition.

Description

  The present invention relates to a shell-like granule or an aggregate thereof, and a filler having the same.

  In surgery involving bone resection or in root regeneration, a structure called a filling material or a filling material is required for the defect. As these fillers, bone tissue compatible fillers such as α-tricalcium diphosphate (α-TCP), β-tricalcium phosphate (β-TCP), and hydroxyapatite are used. Of these, hydroxyapatite is widely used because of its high strength and good biocompatibility (Non-Patent Documents 1 to 3).

  However, when a hydroxyapatite solid is used, it has insufficient connectivity with the surrounding tissue, so a hydroxyapatite powder is agglomerated to form a filler (Non-patent Document 2), concentric circles. The filling material (Patent Document 1) and the like formed in the above have been developed.

  The cement composition is widely used as a dental filler and a material for construction and civil engineering, and its curing means is to add water to the powder and then knead and fill the target site. .

JP 2008-307071 A

Fukase Yasuhiko (1990) Basic research on calcium phosphate cement-Hardening reaction, compressive strength of hardened material and sintering treatment- Nihon University Dentistry, 64, 190-203 Fukase Y, Eanes E D, Takagi S, Chow L C, Brown W E (1990) Setting reactions and compressive strengths of calcium phosphate cements. J Dent Res, 69, 1852-1856 Fukase Y, Wda S, Uehara H, Terraka M, Sato H, Nishiyama M. (1998) Basic studies on hydroxy apatite cement I. setting reaction. J Nihon Univ Sch Dent, 40, 71-76

However, the conventional material for bone regeneration is not sufficient in terms of connectivity with surrounding tissues. In the case of the granule, when the structure of the granule is destroyed at the transplantation site, it is the same as when the powder is transplanted. The significance of transplantation in the form of granules is lost.
Accordingly, an object of the present invention is to provide a bone regeneration material that has excellent connectivity with surrounding tissues due to the shape of granules and that retains good bone regeneration ability even when the granules are broken. .

  Therefore, the present inventor has developed a powdery composition containing two or more calcium phosphate compounds selected from α-tricalcium diphosphate, calcium monohydrogen phosphate and tetracalcium diphosphate and a water-soluble cellulose derivative having hydraulic properties. Paying attention and applying the means for producing a three-dimensional shaped article, shell-like granules or agglomerates thereof containing a hydraulic powder-like composition inside and whose outer shell is formed of a cured product of the composition inside are obtained. It was found that it can be obtained. When the granule structure is destroyed by external pressure, the resulting shell-like granules or aggregates flow out of the internal powder, but since the outflowed powder undergoes a curing reaction due to the moisture present around it, It is useful as a filling material in the medical field because of its ability to repair, and because it is a granule or agglomerate thereof and has a good bond with the surrounding tissue of the filling part, and as a curable material in the construction and civil engineering fields. I found out.

That is, the present invention provides a shell-like granule or an aggregate thereof comprising a hydraulic powder composition inside and an outer shell formed of a cured product obtained by hydrating the powder composition. Is to provide.
Moreover, this invention provides the filler which has the said shell-shaped granule or its aggregate.
Furthermore, the present invention forms a powder layer of a hydraulic powder composition on a stage, supplies water to the predetermined portion to form a hardened layer of a predetermined shape, and a new layer is formed on the hardened layer. Provided is a method for producing a shell-like granule or an aggregate thereof, wherein the powder layer is formed and water is supplied to the predetermined portion to repeat the predetermined hardened layer to laminate the hardened layer. is there.

  Since the shell-like granule or the aggregate of the present invention contains a hydraulic powder that is a raw material of a hardened body that constitutes the shell, if the bone defect portion or the like where moisture is present is filled, the surrounding moisture gradually Hardens to the inside. Further, when the shell-like granule is broken by the external pressure, the powder flowing out from the inside is hardened by the surrounding moisture, and thus has a self-repairing action. Furthermore, since it has the shape of a shell-like granule or an aggregate thereof, it has a good bondability with the transplanted surrounding tissue. Therefore, the shell-like granule or aggregate thereof of the present invention is useful as a filler for dental fillers, bone regeneration fillers, building fillers, etc., and as a cement composition.

It is a figure which shows the example of the aggregation state of a shell-shaped granule. It is a figure which shows the self-restoration state when a shell-like granule is damaged. It is a photograph which shows the state of the shell-like granule obtained in the Example. It is a photograph which shows the state of the shell-like granule obtained in the Example.

  The shell-like granule or the aggregate of the shell of the present invention contains a hydraulic powder composition, and the outer shell is a cured product obtained by hydrating the hydraulic powder composition. It is formed with. Thus, since the internal powder and the raw material of the hardened body of the outer shell are the same, after the whole is hardened, it becomes a uniform granule or its aggregate to the inside.

  The hydraulic powder composition includes (1) a cement composition; (2) two or more calcium phosphate compounds selected from α-tricalcium diphosphate, calcium monohydrogen phosphate, and tetracalcium diphosphate, and a water-soluble cellulose derivative. The powdery composition containing this is mentioned. Here, the cement composition includes a cement composition used for normal construction, as well as a dental cement composition.

  In the powdery composition of (2), two or more calcium phosphate compounds selected from α-tricalcium diphosphate (α-TDP), calcium monohydrogen phosphate (DCPA), and tetracalcium diphosphate (TTCP) are used. Need to use. Even if only one of these is used, it cannot be easily cured by a hydration reaction. More preferable combinations are α-TCP and DCPA, α-TCP and TTCP, or α-TCP and DCPA and TTCP, and three types of combinations (α-DTC) of α-TCP, DCPA, and TTCP are most preferable. The molar ratio of these two or three calcium phosphate compounds used is preferably such that DCPA is 0.5 to 2 mol and TTCP is 0.5 to 2 mol with respect to 1 mol of α-TCP.

  The water-soluble cellulose derivative used in the powdery composition of (2) is important for imparting an appropriate viscosity to the mixture of calcium phosphate compound and water, preventing the calcium phosphate compound from flowing out, and obtaining a desired shape. It is. As a water-soluble cellulose derivative, what is necessary is just a cellulose derivative which is water-soluble and has viscosity, for example, a cellulose ether is mentioned. Examples of the cellulose ether include hydroxyalkyl celluloses such as hydroxyethyl cellulose and hydroxypropyl cellulose; hydroxyalkylalkyl celluloses such as hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, and ethyl hydroxyethyl cellulose. Of these, hydroxyalkyl cellulose is preferable, and hydroxypropyl cellulose is particularly preferable. The amount of the water-soluble cellulose derivative used is preferably 0.001 to 0.50 parts by mass and more preferably 0.005 to 0.50 parts by mass with respect to 1 part by mass of the calcium phosphate compound.

  The hydration reaction of the hydraulic powdery composition is 0.001-0 with respect to 1 part by mass of a hydraulic material (cement in the case of a cement composition, calcium phosphate compound in the case of the composition (2)). Add 1 part by mass of water and cure. Here, the curing conditions differ depending on the desired curing time, and may be performed at 30 to 40 ° C. for about 24 hours, for example.

  The shape of the shell-like granule of the present invention is not limited as long as it contains a hydraulic powder composition inside and the outer shell is formed of a cured product of the composition. The shape may be any of a ball shape, a cube shape, a rectangular parallelepiped shape, a polyhedron shape, and the like. In the case of a biomaterial such as a bone regeneration material, a particle size of 50 μm to 1 cm is preferable. The mass ratio of the outer shell to the inner powder in the granule is not particularly limited, but outer shell: inner powder = 1: 0.2 to 0.2: 1 is preferable from the viewpoint of strength. In addition, the shell-like granule aggregate of the present invention may have any form in which the shell-like granules are aggregated, but the shell-like granules are preferably aggregated while maintaining the form. For example, a regular tetrahedral structure in which four spherical shell-shaped granules are aggregated is particularly preferable because the tetrahedrons aggregate to form a mechanically fitted state and become strong (FIG. 1).

  The shell-like granule or the aggregate thereof of the present invention is preferably produced by a method for producing a three-dimensional shaped article using a hydration reaction. More specifically, a hydraulic powder is formed by forming a powder layer of a hydraulic powder-like composition on a stage of a three-dimensional printer, and spraying and supplying water as if printing from a three-dimensional printer head to a predetermined portion. A hardened layer of a predetermined shape is formed on the body composition, a layer of a new hydraulic powdery composition is formed on the hardened layer, and a hardened layer is formed by spraying water again on the predetermined portion. It is preferable to manufacture by the method of forming a three-dimensional shape by repeating the operation to perform by computer control and laminating a hardened layer. In this three-dimensional shaped article manufacturing method, a predetermined portion for supplying water to each powder layer and a hardened layer having a predetermined shape are, for example, three-dimensional CAD as described in Japanese Patent No. 2620353 and Japanese Patent Application Laid-Open No. 2002-115004. It is performed by computer control using model data.

  The shell-like granule or the aggregate thereof of the present invention has an appropriate strength, and when the granule is broken by external pressure, the spilled hydraulic powdery composition is hardened by the water present at the spill site. Therefore, it has self-healing ability (FIG. 2). Moreover, when water is gradually supplied to the powder inside, the whole is cured. Therefore, it is useful as a material for architectural and civil engineering, a dental filler, a regenerative medicine filler, particularly a bone regeneration filler.

  When the shell-like granule or the aggregate thereof according to the present invention is filled in a bone defect part, a tooth root part, etc., it is a granule or an aggregate thereof, and thus has high connectivity with surrounding tissues and good bone regeneration efficiency. . Further, as a result of gradually supplying water into the shell-like granules at the filling site, the whole is cured. Further, when the granule is broken at the time of filling or the like, the outflowed powdery composition is cured in situ.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited to this at all.

Example 1
(Manufacture of granules)
By the computer control using the three-dimensional CAD model data, regular tetrahedral aggregates in which four spherical shell-like granules were bound were produced.
That is, the α-DTC is placed on the stage of the three-dimensional printer, and a hardened layer having a predetermined shape is formed on the α-DTC by spraying and supplying water to the predetermined portion as if printing from the three-dimensional printer head. A new α-DTC layer was formed thereon, and the operation of spraying water again on the predetermined portion to form a cured layer was repeatedly performed by computer control to form a three-dimensional shape. As a result, a shell-like granule aggregate having a regular tetrahedral structure shown in FIGS. 3 and 4 was produced. 3 and 4, a part of the granule is cut so that the inside can be seen.

Example 2
When external pressure was applied to the granule, as shown in FIG. 2, the outer shell was broken and the α-DTC inside flowed out. If water was present there, the outflowing α-DTC was cured.

  The shell-like granule or the aggregate thereof of the present invention is useful as a filler for bone regeneration when hydroxyapatite is used as a material for construction, civil engineering, dental filler, regenerative medicine, especially as a material. .

Claims (6)

  A shell-like granule or an aggregate thereof comprising a hydraulic powder composition inside and an outer shell formed of a cured product obtained by hydration reaction of the powder composition.   The hydraulic powder composition contains a cement-containing powder composition, or two or more calcium phosphate compounds selected from α-tricalcium diphosphate, calcium monohydrogen phosphate and tetracalcium diphosphate and a water-soluble cellulose derivative. The shell-like granule or aggregate thereof according to claim 1, wherein the shell is a cement hardened body or a hydroxyapatite obtained by hydrating the powder-like composition.   The filler which has the shell-shaped granule of Claim 1 or 2, or its aggregate.   The filler according to claim 3, which is a bone regeneration filler.   Form a powder layer with a hydraulic powder composition on the stage of a three-dimensional printer, and spray and supply water as if printing from a three-dimensional printer head to a predetermined portion to give a predetermined shape to the hydraulic powder composition The operation of forming a hardened layer, forming a new hydraulic powder-like composition layer on the hardened layer, and spraying water on the predetermined portion again to form the hardened layer is repeated by computer control. A method for producing a shell-like granule or an aggregate thereof, wherein a three-dimensional shape is formed by laminating a hardened layer.   The hydraulic powder composition contains a cement-containing powder composition, or two or more calcium phosphate compounds selected from α-tricalcium diphosphate, calcium monohydrogen phosphate and tetracalcium diphosphate and a water-soluble cellulose derivative. 6. The method for producing a shell-like granule or an aggregate thereof according to claim 5, wherein the shell is a cement hardened body or a hydroxyapatite obtained by hydrating the composition.