JPH05123390A - Bone filler - Google Patents

Abstract

(57) [Summary] [Constitution] A bone filler in which calcium phosphate-based powder particles are surrounded by a complex containing carboxylmethyl chitin and collagen and / or gelatin. [Effect] By using the bone filling material 1 of the present invention, an implant which is not toxic to the living body and which is free from shaking and outflow after filling and which shows growth and production of new bone is realized.

Description

Detailed Description of the Invention

[0001]

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

[0002]

2. Description of the Related Art Bone defects and voids may occur due to surgery of bone fractures and bone tumors. In recent years, artificial bone filling materials have been developed for prosthesis of 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 propose bone filling materials in which a polymeric material such as chitin, collagen, polyvinyl alcohol or the like and a calcium phosphate compound are combined. A non-toxic polymer material is used to improve the operability when filling the material and to prevent shaking after filling.

[0004]

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

[0005]

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

[0006]

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

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

As the calcium phosphate powder,
Hydroxyapatite, tricalcium phosphate, and calcium phosphate-based glass are clinically applied.
It was discovered that tricalcium phosphate, calcium phosphate-based glass, and hydroxyapatite were excellent in calcium and phosphorus elution by an elution experiment in a simulated body fluid. When the amount of tricalcium phosphate is 70 wt% or more, the solution becomes acidic and the calcium phosphate-based glass is 20%.
If it is more than wt%, the immersion liquid becomes alcalic. It is not preferable that a prosthesis for a living body elutes an acidic or alkaline substance in the living body, since it adversely affects the living body. Therefore, the above calcium phosphate-based powder contains tricalcium phosphate 0-70 wt% and calcium phosphate-based glass 0-70 wt%.
Those containing 20 wt% are preferable.

On the other hand, tricalcium phosphate and hydroxyapatite are mixed with Ca (HO) in phosphoric acid aqueous solution.
Although it can be obtained by heat-treating the obtained product at a temperature of 900-1300 ° C. Since tricalcium phosphate reacts well with water, it is pulverized by dry method, and hydroxyapatite is pulverized by a dry method or a 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-ground.

Calcium phosphate powder containing 0 to 70 wt% of tricalcium phosphate, 0 to 20 wt% of calcium phosphate glass and hydroxyapatite obtained by the above-mentioned method, collagen and / or gelatin.
The bone filler is obtained by immersing in an aqueous solution of carboxymethyl chitin containing 10 to 50 wt%, defoaming, air-drying, and then vacuum thermal crosslinking at 100 to 160 ° C.

Example 1 4 g of carboxymethyl chitin and gelatin in 100 ml of sterilized water
2 g was added to prepare a carboxymethyl chitin / gelatin solution. 60 g of wet-milled hydroxyapatite with an average particle size of 5 μm at 1000 ° C., 35 g of dry-pulverized average particle size of 55 μm of tricalcium phosphate at 1200 ° C., and dry-pulverized apatite / wow with an average particle size of 45 μm 5 g of a calcium phosphate-based crystallized glass prepared from a rustonite mixed powder was immersed in the carboxymethyl chitin / gelatin solution, defoamed, air-dried, and then thermally vacuum-crosslinked at 140 ° C. for 24 hours. Then, the bone filler 1 comprising the carboxylmethyl chitin complex 3 and the calcium phosphate-based powder particles 2 was prepared by classifying to an average particle size of 350 μm.

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

As a control, hydroxyapatite granules (hereinafter abbreviated as hydroxyapatite granules) surrounded by carboxylmethyl chitin in an aqueous solution were prepared, and the bone filling material 1 of the present invention was separately prepared from the femur of a rabbit. The cells were embedded in the cells and observed over time. 1 week after implantation, 4
After laps and 8 laps, the animals were sacrificed, the surrounding tissues were detected and fixed with formalin solution, and after decalcification, resin embedding and staining were performed to prepare pathological specimens.

[1 week after implantation] In the bone filling material 1 of the present invention, partial elution was observed, and formation of new bone and osteoblasts was observed in the periphery. On the other hand, some osteoblast formation was observed around the hydroxyapatite granules as a comparative example.

[4 weeks after implantation] In the bone filling material 1, further elution proceeded, and active growth of new bone was observed in the surrounding area. On the other hand, the hydroxyapatite granules of Comparative Example also showed some growth and formation of new bone around them.

[8 weeks after implantation] The bone filler 1 did not show elution, but was surrounded by new bone.

On the other hand, a part of fibrous tissue was observed around the hydroxyapatite granules of the comparative example, but the newly-generated new bones only partially surrounded them.

Example 2 To 100 ml of sterilized water, 2 g of carboxymethyl chitin and 2 g of collagen were added to prepare a carboxymethyl chitin / collagen solution. 20 g of dry crushed hydroxyapatite with an average particle size of 50 μm at 1000 ° C., 35 g of dry crushed average particle size of 40 μm of tricalcium phosphate at 1300 ° C., and dry crushed apatite / wollast with an average particle size of 45 μm 30 g of a calcium phosphate glass prepared from a night mixed powder was immersed in the above-mentioned carboxymethyl chitin / collagen solution, defoamed, air-dried, and then heat-crosslinked in vacuum at 100 ° C. for 12 hours. Then, the bone filler 1 comprising the carboxylmethyl chitin complex 3 and the calcium phosphate-based powder particles 2 was prepared by classifying to an average particle size of 500 μm.

The above bone filling material 1 was filled around the fourth molar of the upper jaw of a beagle dog experimentally causing periodontal disease and observed over time.

The bone filler 1 did not flow out in the observation up to 2 months, and no shaking was observed in the X-ray examination. After slaughtering the beagle dogs, a histological examination showed that new bone growth and formation were found around the teeth, indicating that good periodontal support tissue was regenerated.

As described above, the bone filling material 1 of the present invention has biocompatibility and bone forming ability superior to those of the bone filling material of calcium phosphate type powder particles surrounded by carboxymethyl chitin of the prior art. It was proved.

Example 3 To 100 ml of sterilized water, 2 g of carboxymethyl chitin and 2 g of collagen were added to prepare a carboxymethyl chitin / collagen solution. 35 g of dry-ground crushed hydroxyapatite with an average particle size of 70 μm at 1000 ° C. and 50 g of dry-crushed tricalcium phosphate with an average particle size of 60 μm baked at 1300 ° C. were immersed in the above carboxymethyl chitin / collagen solution to defoam. After air-drying, at a temperature of 100 ° C 14
It was vacuum heat cross-linked for a time. After that, the bone filler 1 composed of the carboxylmethyl chitin complex 3 and the calcium phosphate-based powder particles 2 was prepared by classifying to an average particle size of 450 μm.

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

The bone filling material 1 was filled around the fourth molar of the upper jaw of a beagle dog experimentally causing periodontal disease, and observed over time.

The bone filler 1 did not flow out in the observation up to 2 months, and no shaking was observed in the X-ray examination. After slaughtering the beagle dogs, a histological examination showed that new bone growth and formation were found around the teeth, indicating that good periodontal support tissue was regenerated.

Further, calcium phosphate glass produced from dry-ground apatite / wollastonite mixed powder having an average particle size of 45 μm and wet-ground 10 having an average particle size of 50 μm.
Bone filler 1 prepared by the above method by immersing hydroxyapatite calcined at 00 ° C in the above carboxymethyl chitin / collagen solution, and dry-ground average particle size 45μ
30 g of calcium phosphate-based glass made from m apatite / wollastonite mixed powder and 50 g of dry-ground tricalcium phosphate with an average particle size of 60 μm and calcined at 1300 ° C. were immersed in the carboxymethyl chitin / collagen solution described above Similar results were obtained in the animal experiment by the above-mentioned method for the bone filling material 1 prepared in 1.

Example 4 To 100 ml of sterilized water, 2 g of carboxymethyl chitin, 1 g of collagen and 1 g of gelatin were added, and carboxymethyl chitin /
A collagen / gelatin solution was prepared. 90 g of dry-crushed hydroxyapatite having an average particle size of 80 μm and calcined at 1000 ° C. was immersed in the above-mentioned carboxymethyl chitin / collagen solution, defoamed and air-dried, and then vacuum heat-crosslinked for 13 hours at a temperature of 100 ° C. Then, the bone filler 1 was prepared by classifying to an average particle size of 700 μm and comprising a carboxymethyl chitin complex 3 and calcium phosphate powder 2 of hydroxyapatite 2c.

As shown in FIG. 4, in the bone filling material 1, the above-mentioned carboxymethyl chitin complex 3 containing collagen is swelled after filling, and the calcium phosphate powder particles 2 of the hydroxyapatite 2c are surrounded and fixed.

The bone filling material 1 was filled around the fourth molar of the upper jaw of a beagle dog experimentally causing periodontal disease, and observed over time.

Bone filler 1 did not flow out in the observation up to 2 months, and no shaking was observed in the X-ray examination. After slaughtering the beagle dogs, a histological examination showed that new bone growth and formation were found around the teeth, indicating that good periodontal support tissue was regenerated.

Calcium phosphate-based glass prepared from dry-ground apatite / wollastonite mixed powder having an average particle size of 45 μm is used as the above-mentioned carboxymethyl chitin /
Bone filler 1 produced by the above method by immersing it in a collagen / gelatin solution, and 1300 ° C with an average particle size of 60 μm after dry pulverization
Similar results were obtained in the animal experiment by the above-mentioned method with respect to the bone filler 1 produced by the above-mentioned method by immersing the tricalcium phosphate calcined in 1. in the above-mentioned carboxymethyl chitin / collagen solution.

The bone filling material 1 of the present invention is used as a product.
As shown in FIG. 5, the calcium phosphate-based powder particles 2 and the carboxylmethyl chitin complex 3 particles are mixed together, or as shown in FIG. Body 3
The coated product is put in a container Y such as a bottle for sale or storage.

As described above, the bone filling material 1 of the present invention has biocompatibility and bone forming ability superior to those of the bone filling material made of calcium phosphate-based powder particles surrounded by carboxymethyl chitin, which is a conventional technique. It was proved.

[0035]

EFFECT OF THE INVENTION By using the bone filling material 1 of the present invention, it is possible to realize an implant which is free from toxicity to the living body and causes no growth or growth of new bone without any shaking or outflow after filling.

[Brief description of drawings]

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

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

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

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

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

FIG. 6 is a partially enlarged cross-sectional view showing another embodiment of the bone filling material of the present invention at the 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)

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