JP2984112B2 - Bone filler - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an implant for a living body, and more particularly to a bone filling material used for hard tissues of bones and teeth such as periodontal bone defects.

[0002]

2. Description of the Related Art Bone defects and voids may occur due to surgery for fractures and bone tumors. In recent years, artificial bone filling materials have been developed to prosthesis for such bone defects and voids. Among them, calcium phosphate-based powders such as hydroxyapatite and tricalcium phosphate are currently widely used, and many animal experiments have been carried out and also used in general clinical practice.

Japanese Patent Application Laid-Open Nos. 62-221358 and 1-181871 disclose a bone filling material in which a polymer material such as chitin, collagen, polyvinyl alcohol and the like and a calcium phosphate compound are complexed. A non-toxic polymer material is used to improve the operability at the time of filling the material and to prevent swaying after the filling.

[0004]

2. Description of the Related Art The bone filler described in the above publication is very effective for preventing movement and swaying during filling of living tissue. However, when chitin and collagen are used, the growth and production of bone tissue are partially induced, but in other cases, the growth and production of bone tissue are not induced. Therefore, the development of a bone filler that induces the growth and production of new bone has been desired.

[0005]

In order to solve the above-mentioned problems, the present invention provides a bone filler comprising calcium phosphate-based powder particles and a complex containing carboxymethyl chitin and collagen and / or gelatin.

[0006]

EXAMPLES The present inventors have studied the growth and formation of new bone for various polymer materials. Among them, it was found that the growth and production of new bone on chitin and its derivative carboxymethyl chitin were good. In general, chitin has a problem that it is difficult to dissolve in water and is difficult to mold. However, carboxymethyl chitin can be easily dissolved in a solvent such as water or ethanol and formed into a film or sponge. Furthermore, it was found that the complexation with collagen or gelatin having better moldability and similar bioreactivity than collagen further promotes the growth and formation of new bone. Furthermore, similar results were obtained when collagen and gelatin were mixed and used.

At this time, collagen and / or gelatin
When the amount is less than 10 wt%, the growth of new bone is not significantly different from that of carboxymethyl chitin alone.
%, No remarkable difference from collagen or gelatin alone was observed.

[0008] As the calcium phosphate powder,
Hydroxyapatite, tricalcium phosphate and calcium phosphate glass have been clinically applied.
Elution experiments in simulated body fluids revealed that tricalcium phosphate, calcium phosphate glass, and hydroxyapatite were superior in eluting calcium and phosphorus. If the tricalcium phosphate is 70 wt% or more, the solution becomes acidic and the calcium phosphate glass becomes 20%.
If the content is more than wt%, the immersion liquid becomes alkaline. It is not preferable that the prosthesis to the living body elutes an acidic or alkaline substance in the living body because it has an adverse effect on the living body. Therefore, the calcium phosphate powder contains 0 to 70% by weight of tricalcium phosphate and 0 to 70% by weight of calcium phosphate glass.
Those containing 20 wt% are preferred.

[0009] On the other hand, tricalcium phosphate and hydroxyapatite are mixed with Ca (HO) in an aqueous phosphoric acid solution.
Can be obtained by heat-treating the resulting product at a temperature of 900 to 1300 ° C. Tricalcium phosphate reacts well with water and is pulverized dry, and hydroxyapatite is pulverized by a dry or wet method.

As the calcium phosphate glass, bioglass or crystallized glass containing apatite and wollastonite is used. Since these materials also have an affinity for water, they are dry-pulverized.

The calcium phosphate-based powder containing 0 to 70% by weight of tricalcium phosphate, 0 to 20% by weight of calcium phosphate-based glass and hydroxyapatite, and collagen and / or gelatin obtained by the above method are used.
It is immersed in an aqueous solution of carboxymethyl chitin containing 10 to 50% by weight, defoamed, air-dried, and then subjected to vacuum thermal crosslinking at 100 to 160 ° C to obtain a bone filler.

Example 1 4 g of carboxylmethyl chitin and gelatin in 100 ml of sterilized water
2 g was added to prepare a carboxymethyl chitin / gelatin solution. 60 g of wet-ground pulverized hydroxyapatite with an average particle size of 5 μm, baked at 1000 ° C, 35 g of dry-ground pulverized tricalcium phosphate with an average particle size of 55 μm, and 35 g of dry-ground pulverized apatite / water with an average particle size of 45 μm 5 g of a calcium phosphate crystallized glass prepared from the lastonite mixed powder was immersed in the carboxymethyl chitin / gelatin solution, defoamed, air-dried, and thermally crosslinked under vacuum at 140 ° C. for 24 hours. Thereafter, the mixture was classified into an average particle diameter of 350 μm to prepare a bone filler 1 composed of the carboxylmethyl chitin complex 3 and the calcium phosphate powder 2.

As shown in FIGS. 1 and 2, in the bone filling material 1, the above-mentioned carboxymethyl chitin complex 3 containing gelatin swells after filling, and the calcium phosphate glass 2a, the tricalcium phosphate 2b, and the hydroxyapatite 2c calcium phosphate powder particles 2
Surround and secure. In addition, hydroxyapatite 2c
When wet pulverized, they are almost uniformly dispersed as fine particles throughout the bone filler 1 as shown in FIG.

As a control, hydroxyapatite granules (hereinafter abbreviated as hydroxyapatite granules) surrounded by an aqueous solution of carboxymethyl chitin were prepared, and this and the bone filler 1 of the present invention were separately separated from the femur of a rabbit. And observed over time. 1 week after implantation, 4
After 8 weeks, the animals were sacrificed, and the surrounding tissues were detected and fixed with formalin solution. After decalcification, resin embedding and staining were performed to prepare pathological specimens.

[One week after implantation] In the bone filler 1 of the present invention, partial elution was observed, and formation of new bone and osteoblasts was observed around the bone filler. On the other hand, some osteoblasts were generated around the hydroxyapatite granules as a comparative example.

[Four Weeks after Implantation] In the bone filler 1, the elution further progressed, and active growth of new bone was found around the bone filler 1. On the other hand, the hydroxyapatite granules of the comparative example also showed a slight growth of new bone around.

[Eight weeks after implantation] In the bone filling material 1, no elution was observed, but the periphery was surrounded by new bone.

On the other hand, some fibrous tissues were found around the hydroxyapatite granules of the comparative example, but the newly formed new bone only partially surrounded it.

Example 2 Carboxymethyl chitin / collagen solution was prepared by adding 2 g of carboxymethyl chitin and 2 g of collagen to 100 ml of sterilized water. 20 g of dry-ground hydroxyapatite with an average particle size of 50 μm fired at 1000 ° C., 35 g of dry-ground pulverized tricalcium phosphate with an average particle size of 40 μm fired at 1300 ° C., and apatite / wollast with an average particle size of 45 μm dry-ground 30 g of a calcium phosphate glass prepared from the knight mixed powder was immersed in the carboxymethyl chitin / collagen solution, defoamed, air-dried, and thermally crosslinked under vacuum at 100 ° C. for 12 hours. Thereafter, the mixture was classified into an average particle diameter of 500 μm to prepare a bone filler 1 comprising the carboxylmethyl chitin complex 3 and the calcium phosphate powder 2.

The above-mentioned bone filler 1 was filled around the upper molar of the upper jaw of a beagle dog experimentally caused periodontal disease, and observed over time.

In the observation up to two months, no outflow of the bone filler 1 was observed, and no fluctuation was observed in the X-ray examination. Histological examination was performed after sacrifice of the Beagle dog. As a result, new bone growth was generated around the teeth, and it was confirmed that good periodontal support tissue had been regenerated.

As described above, the bone filler 1 of the present invention has better biocompatibility and bone forming ability than the conventional bone filler composed of calcium phosphate-based powder particles surrounded by carboxymethyl chitin. It was proved.

Example 3 2 g of carboxymethyl chitin and 2 g of collagen were added to 100 ml of sterilized water to prepare a carboxymethyl chitin / collagen solution. 35 g of dry-ground pulverized hydroxyapatite with an average particle size of 70 μm fired at 1000 ° C and 50 g of dry-ground pulverized tricalcium phosphate with an average particle size of 60 μm fired at 1300 ° C are immersed in the above carboxymethyl chitin / collagen solution and defoamed. After air-drying, at a temperature of 100 ℃ 14
Vacuum thermally crosslinked for hours. Thereafter, the mixture was classified into an average particle diameter of 450 μm to prepare a bone filler 1 comprising the carboxylmethyl chitin complex 3 and the calcium phosphate-based powder particles 2.

As shown in FIG. 3, in the bone filling material 1, the above-mentioned carboxymethyl chitin complex 3 containing collagen swells after filling, and the tricalcium phosphate 2
b, and the calcium phosphate-based powder particles 2 of hydroxyapatite 2c are surrounded and fixed.

The bone filler 1 was filled around the upper molars of the upper jaw of a beagle dog experimentally caused periodontal disease, and observed over time.

In the observation up to two months, no outflow of the bone filler 1 was observed, and no fluctuation was observed in the X-ray examination. Histological examination was performed after sacrifice of the Beagle dog. As a result, new bone growth was generated around the teeth, and it was confirmed that good periodontal support tissue had been regenerated.

A calcium phosphate glass prepared from a dry-ground apatite / wollastonite mixed powder having an average particle diameter of 45 μm and a wet-ground calcium phosphate glass having an average particle diameter of 50 μm are used.
Hydroxyapatite calcined at 00 ° C. is immersed in the above-mentioned carboxymethyl chitin / collagen solution, and the bone filler 1 prepared by the above-mentioned method is dried and pulverized to an average particle size of 45 μm.
30 g of calcium phosphate glass prepared from apatite / wollastonite mixed powder of 50 m and 50 g of dry-ground pulverized tricalcium phosphate having an average particle diameter of 60 μm and fired at 1300 ° C. are immersed in the above-mentioned carboxymethyl chitin / collagen solution and Similar results were obtained in the animal experiment using the bone filler 1 prepared in the above-mentioned method.

Example 4 To 100 ml of sterile water, 2 g of carboxymethyl chitin, 1 g of collagen and 1 g of gelatin were added.
A collagen / gelatin solution was prepared. 90 g of dry-ground hydroxyapatite having an average particle size of 80 μm and calcined at 1000 ° C. was immersed in the carboxymethyl chitin / collagen solution, defoamed and air-dried, followed by vacuum thermal crosslinking at 100 ° C. for 13 hours. Thereafter, the mixture was classified to an average particle diameter of 700 μm to prepare a bone filler 1 comprising a carboxylmethyl chitin complex 3 and calcium phosphate-based powder particles 2 of hydroxyapatite 2c.

As shown in FIG. 4, in the bone filler 1, the above-mentioned carboxymethyl chitin complex 3 containing collagen swells after filling, and surrounds and fixes the calcium phosphate-based powder particles 2 of hydroxyapatite 2c.

The bone filler 1 was filled around the upper molar of the upper jaw of a beagle dog experimentally caused periodontal disease, and observed over time.

In the observation up to two months, no outflow of the bone filler 1 was observed, and no fluctuation was observed in the X-ray examination. Histological examination was performed after sacrifice of the Beagle dog. As a result, new bone growth was generated around the teeth, and it was confirmed that good periodontal support tissue had been regenerated.

Further, the calcium phosphate glass prepared from the dry-ground pulverized apatite / wollastonite mixed powder having an average particle size of 45 μm was mixed with the above carboxymethyl chitin /
Bone filler 1 immersed in a collagen / gelatin solution and prepared as described above, and dry-ground at 1300 ° C. with an average particle size of 60 μm
The same result was obtained in the animal experiment by the above-mentioned method for the bone filler 1 prepared by the above-mentioned method by immersing the tricalcium phosphate calcined in the above-mentioned method in the above-mentioned carboxymethyl chitin / collagen solution.

The bone filler 1 of the present invention is commercially available.
In a state where the calcium phosphate-based powder particles 2 and the particles of the carboxymethyl chitin complex 3 are mixed as shown in FIG. 5, or as shown in FIG. Body 3
Is coated in a container Y such as a bottle and sold or stored.

As described above, the bone filler 1 of the present invention has better biocompatibility and bone forming ability than the conventional bone filler composed of calcium phosphate-based powder particles surrounded by carboxymethyl chitin. It was proved.

[0035]

The use of the bone filling material 1 of the present invention realizes an implant which is not toxic to living organisms, does not shake after filling, and shows growth and production of new bone without outflow.

[Brief description of the drawings]

FIG. 1 is a partially enlarged cross-sectional view showing a state after filling of a bone filler of the present invention using wet-ground hydroxyapatite.

FIG. 2 is a partially enlarged cross-sectional view showing a state after filling of the bone filler of the present invention using dry-ground hydroxyapatite.

FIG. 3 is a partially enlarged sectional view showing a state after filling with the bone filler of the present invention.

FIG. 4 is a partially enlarged sectional view showing a state after filling with the bone filler of the present invention.

FIG. 5 is a partially enlarged cross-sectional view showing one embodiment of a bone filler of the present invention at a commercial stage.

FIG. 6 is a partially enlarged cross-sectional view showing another embodiment of the bone filler of the present invention at a commercial stage.

[Explanation of symbols]

 1: Bone filler 2a: Calcium phosphate glass 2b: Tricalcium phosphate 2c: Hydroxyapatite 3: Carboxymethyl chitin complex Y: Container

Claims (1)

(57) [Claims] 1. A bone filler comprising calcium phosphate powder particles and a complex containing carboxymethyl chitin and collagen and / or gelatin.