Patent Application
20100222883
The present invention relates to an artificial bone used for bone transplantation and the like. More particularly, the present invention relates to an artificial bone having substantially unidirectionally-oriented pores for the improvement of osteoconductivity.
In general, an artificial bone having a pore structure is widely used to secure osteoconductivity in bone transplantation and the like. As such an artificial bone having a pore structure, for example, a calcium phosphate sintered body wherein many pores are densely distributed three-dimensionally, and a skeleton wall compartmentalizing adjacent pores has linked sphere-like opened pores communicating with them (see patent document 1) is conventionally known. However, the osteoconductivity thereof is not entirely satisfactory. Moreover, it is disclosed that a sintered body having unidirectionally-oriented pores with a diameter of 10-500 μm is a ceramic material suitable as an implant material (patent document 2).
Generally, when a material having substantially unidirectionally-oriented pores is used as an artificial bone, the maximum osteoconductivity can be exhibited by implanting the bone while setting the pore orientation in an appropriate direction. However, it is extremely difficult to visually recognize the direction of orientation of fine pores having a diameter of about 10-500 μm, and misidentification of the implantation direction of an artificial bone is feared to cause decreased treatment effects such as elongated time necessary for healing and the like. Moreover, since the initial strength of the artificial bone varies depending on the oriented direction of the pores, it is important to implant an artificial bone in an affected part by setting the oriented direction of the pores to a desired direction based on the understanding of the oriented direction of the pores in the artificial bone.
The present invention has been made in view of such situation, and aims to provide an artificial bone capable of easily and accurately confirming the direction of substantially unidirectionally-oriented pores to achieve good osteoconductivity.
The present inventors have conducted intensive studies in an attempt to solve the aforementioned problems and completed the present invention having the following characteristics.
Accordingly, the present invention relates to
Since the artificial bone of the present invention has a marker showing the direction of orientation of the substantially unidirectionally-oriented pores, for example, a physician can easily and accurately know the direction along which the artificial bone is to be implanted during bone transplantation.
a) and
a)-(c) are perspective views schematically showing a seventh embodiment (3 embodiments) of the artificial bone of the present invention.
a)-(c) are perspective views schematically showing an eighth embodiment (3 embodiments) of the artificial bone of the present invention.
The present invention is explained in detail in the following by referring to preferable embodiments thereof.
The artificial bone of the present invention has, as shown by artificial bone 10 of said embodiment, substantially unidirectionally-oriented pores 2 in the inside of the material (artificial bone main body) 1. The pores being “unidirectionally oriented” here mean that pores extending in the uniaxial direction are present and the long axis direction of such pores is arranged to be unidirectional. More specifically, for example, the long axis direction of not less than half, preferably not less than 80%, more preferably not less than 90%, of the pores extending in the uniaxial direction in the material (artificial bone) is aligned unidirectionally. In addition, “substantially unidirectional” means that the long axis of pores are aligned to fall within the crossing angle of 30°.
The material of the artificial bone of the present invention is not subject to any particular limitation. Examples thereof include calcium phosphate, silica, titania, zirconia and the like. Among these, calcium phosphate is preferable. Preferable examples of calcium phosphate include hydroxyapatite, fluorapatite, chlorapatite, tricalcium phosphate, calcium metaphosphate, tetracalcium phosphate, calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate and the like. In the material of the present invention, a part of Ca component of calcium phosphate may be substituted by one or more kinds selected from Sr, Ba, Mg, Fe, Al, Y, La, Na, K, Ag, Pd, Zn, Pb, Cd, H and other rare earths. In addition, a part of (PO4) component may be substituted by one or more kinds selected from VO4, BO3, SO4, CO3, SiO4 and the like. Furthermore, a part of (OH) component may be substituted by one or more kinds selected from F, Cl, O, CO3, I and Br.
For bone formation, calcium phosphate is more preferably hydroxyapatite, fluorapatite, chlorapatite or tricalcium phosphate, most preferably hydroxyapatite or tricalcium phosphate, and calcium phosphate may form a composite with collagen and the like. Calcium phosphate may be derived from natural mineral, or may be synthesized by various wet processes, dry processes and the like.
An artificial bone having substantially unidirectionally-oriented pores can be produced by a known method.
When artificial bone 10 in the above-mentioned embodiment is to be produced, for example, a cylindrical container having a brass plate as a basal plate and a vinyl chloride resin as a side wall is prepared. On the other hand, a slurry obtained by dispersing or dissolving hydroxyapatite and, where necessary, an organic binder (e.g., one or more kinds selected from collagen, gelatin, polylactic acid, polyacrylic acid, polyethylene glycol, polyvinyl alcohol and the like) in water is prepared. The slurry is filled in the above-mentioned cylindrical container, and the basal plate is cooled with liquid nitrogen and the like to not higher than the coagulation point of the slurry to foam needle-like ice in the slurry from the base. As a different method, a cylindrical container containing a slurry is inserted (immersed) in a refrigerant cooled to not higher than the coagulation point of the slurry by, for example, a suitable power source such as constant-speed motor and the like to form needle-like ice in the slurry from the base of the cylindrical container. In addition, the ice is sublimated and removed under vacuum and, where necessary, the residue is sintered at 1000° C. or above to give an artificial bone (having a cylindrical external shape) 10 having substantially unidirectionally-oriented pores 2. When a prism-shaped container, cylindroid-shaped container and the like are used as the container to fill in the above-mentioned slurry, an artificial bone having a prism-like or cylindroid-like external shape and the like can be obtained.
The shape (external shape) of the artificial bone of the present invention is not particularly limited, and it may be a shape other than the above-mentioned cylindrical shape, prism-like shape and cylindroid-like shape. That is, the artificial bone of the present invention encompasses one obtained by processing (post-processing) an artificial bone having a column-like shape into a desired shape, one obtained by joining a plurality of column-like artificial bones and post-processed artificial bones by a suitable joining method and the like. That is, a plurality of bone parts having substantially unidirectionally-oriented pores may be combined.
While the size of the substantially unidirectionally-oriented pores is not particularly limited, the diameter (diameter of section vertical to the long axis of pores) is about 10-500 μm, the length (length of pores in the long axis direction) is preferably not less than 5 mm, more preferably not less than 7 mm, further preferably not less than 10 mm. The upper limit of the length is not particularly limited.
The porosity is generally 40-90%, and preferably not less than 50%, more preferably not less than 80%, of all pores are constituted with “substantially unidirectionally-oriented pores”.
The artificial bone of the present invention has substantially unidirectionally-oriented pores, and a marker showing the pore orientation direction. The marker may be any as long as it can be recognized at least visually or by a tactile sense and the form thereof is not particularly limited.
The artificial bone 10 in the above-mentioned embodiment (
In the present invention, line symbol 3a is not particularly limited as long as the orientation direction of pores 2 can be easily and accurately recognized. As shown in the example of the above-mentioned
The protrusion 3b and pit 3c as such markers preferably have a protrusion height or pit depth of about 0.1-2 mm so that they can be at least recognized visually or by tactile sense. With a height or depth in such range, the sense of concave convex can be obtained with human fingers and the like, and can also be visually recognized since the reflectance of the light at the marked portion on the surface of the artificial bone is different from that of the surrounding area.
In addition, the shape of protrusion 3b and pit 3c is not particularly limited as long as it enables easy and accurate recognition of the pore direction. In the embodiment of
In the artificial bone of the present invention, the marker showing the direction of orientation of substantially unidirectionally-oriented pores may be constituted with a composite of a line symbol and a protrusion, or a line symbol and a pit. That is, for example, it may be protrusion 3b and pit 3c shown in
Moreover, the artificial bone of the present invention also includes, as mentioned above, an artificial bone comprising a plural combinations of bone parts having substantially unidirectionally-oriented pores. In such artificial bone, a marker (line symbol, protrusion, pit etc.) is attached to each bone part having substantially unidirectionally-oriented pores, whereby the direction of orientation of unidirectionally-oriented pores in each bone part can be known easily.
In the present invention, the size of the marker comprising a line symbol, protrusion, pit etc. is not particularly limited. For easy recognition, however, a size containing a part with a length of one direction of about 3-50 mm is preferable. That is, when a marker is, for example, a linear line symbol shown in
A marker in the form of a line symbol or protrusion can be eliminated as necessary by a diamond bar or disk and the like when using the artificial bone (when artificial bone is actually implanted in the body).
In the present invention, examples of the marker showing the direction of orientation of unidirectionally-oriented pores (hereinafter sometimes to be simply referred to as “pore orientation direction”) besides the aforementioned embodiments include those shown in
a) and (b) show embodiments wherein the surface of an artificial bone is marked with dot symbols. In the artificial bone 40A shown in
In the embodiments of artificial bones 40C and 40D shown in
In addition, artificial bone 40E shown in
The artificial bones 50A-50C shown in
In the artificial bones shown in
While the size of the dot symbols 41a-41c, arrow symbol 43, triangle symbol 44 and the like is not particularly limited, a size easily recognized visually, which does not require attachment of an excess amount of dye, is preferable. For example, when the dot symbol has a circular shape, it generally has a diameter of about 0.5-3.0 mm, and when the dot symbol has a shape other than a circular shape, it appropriately has a size (area) corresponding to the area of a circle having a diameter of 0.5-3.0 mm. In addition, arrow symbol 43, triangle symbol 44 and the like also preferably have a size equivalent to or slightly larger than that of such circular dot symbol.
Such dot symbols 41a-41c, line symbol 42, arrow symbol 43, triangle symbol 44 and the like may be formed not only by coloring but also by complexing with a pit or protrusion, like the line symbol 3a of artificial bone 10 in the aforementioned
The specific examples of the artificial bone of the present invention as mentioned above are embodiments wherein the marker showing the pore orientation direction is constituted with a symbol marked on the surface of the artificial bone. In the artificial bone of the present invention, the marker showing the pore orientation direction may be constituted with a part or the whole of the steric shape of the artificial bone.
a)-(c) are embodiments wherein the markers showing the pore orientation direction are constituted with the steric shapes of the whole artificial bones. The artificial bone 60A shown in
As in the artificial bones 60A-60C and 70 shown in these
As long as an embodiment wherein the steric shape of a part or the whole of an artificial bone constitutes a marker showing the pore orientation direction does not require marking of a symbol on the surface of the artificial bone with dye and the like, which eliminates the need to consider safety and the like of dye and the like to the body. In addition, even when an artificial bone actually used (when artificial bone is implanted in the body) is colored by contact with blood and the like, and a symbol marked with a dye and the like cannot be identified, it provides an advantage that the pore orientation direction can be recognized by vision or tactile sense.
The present invention is explained more specifically in the following by referring to Examples.
Ten cylindrical containers (inner diameter 16 mm, height 20 mm without basal plane) made of vinyl chloride resin were directly placed on a discal cooling plate (diameter 120 mm), and a slurry obtained by dispersing or dissolving hydroxyapatite (17 wt %) and gelatin (4 wt %) as an additive in distilled water was filled in the containers by 1 g for each container. By cooling the cooling plate with a freezing apparatus, slurry was cooled at a freezing rate of 0.015 ml/min to allow formation of needle-like ice in the slurry. The thus-obtained frozen body was sublimated and dried under vacuum, and the green body was sintered at 1200° C. to give an artificial bone having unidirectionally oriented pores.
A slurry (10 g) obtained by dispersing or dissolving hydroxyapatite (21.8 wt %) and gelatin (4.8 wt %) as an additive in distilled water was filled in a 15 ml centrifugation tube with an inner diameter of about 16 mm (made of polypropylene resin, manufactured by Greiner, Germany) as a container. The container was immersed in an ethyl alcohol bath cooled to −20° C. at a rate of 20 mm/h to allow formation of needle-like ice in the slurry. The thus-obtained frozen body was sublimated and dried under vacuum, and the green body was sintered at 1200° C. to give an artificial bone having unidirectionally-oriented pores.
The artificial bones obtained in Production Examples A and B were cut in a cylindrical shape (φ6 mm, height 8 mm) by a cutting machine, MODELA Pro MDX-650, manufactured by Roland. Thereafter, β-carotene (0.1%) dissolved in ethyl alcohol was used as a dye and a line symbol (line width 0.3 mm, length 8 mm) as shown in
The above-mentioned artificial bones obtained in Production Examples A and B were cut in a cylindrical shape (φ6 mm, height 8 mm) by a cutting machine, MODELA Pro MDX-650, manufactured by Roland, and a protrusion (substantially cuboid, length 1 mm×width 1 mm, height 8 mm) was simultaneously formed on the cylindrical side face from the basal plane to the top face as shown in
The above-mentioned artificial bones obtained in Production Examples A and B were cut in a cylindrical shape (φ6 mm, height 8 mm) by a cutting machine, MODELA Pro MDX-650, manufactured by Roland. Furthermore, a pit (V-shaped groove of cross section, opening width 1 mm, depth 1 mm, height 8 mm) was formed on the cylindrical side surface from the basal plane to the top face as shown in
The above-mentioned artificial bones obtained in Production Examples A and B were cut in a cylindrical shape (φ6 mm, height 8 mm) by a cutting machine, MODELA Pro MDX-650, manufactured by Roland, and a protrusion (substantially cuboid, length 1 mm×width 1 mm, height 8 mm) was simultaneously formed on the cylindrical side surface from the basal plane to the top face as shown in
The above-mentioned artificial bones obtained in Production Examples A and B were cut into a right circular cone shape (diameter of basal plane 6 mm, height 8 mm) wherein the axis center thereof is substantially in parallel with the pore orientation direction (long axis of pores) by a cutting machine, MODELA Pro MDX-650, manufactured by Roland, whereby artificial bones were obtained.
Since the artificial bone of the present invention contains substantially unidirectionally-oriented pores as well as a marker showing the pore orientation direction, the direction along which the artificial bone is to be implanted can be easily and accurately known during bone transplantation. Hence, physicians can certainly implant an artificial bone having substantially unidirectionally-oriented pores in an appropriate direction during bone transplantation, and therefore, treatment effects are expected to be improved.
This application is based on a patent application No. 2007-237051 filed in Japan, the contents of which are incorporated in full herein.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2007-237051 | Sep 2007 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP2008/065727 | 9/2/2008 | WO | 00 | 3/12/2010 |
