JP3465194B2 - Bone formation promoter, method for producing the same, and composition using the same - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an osteogenesis promoter, a method for producing the same, and a composition containing the osteogenesis promoter. More specifically, a new osteogenesis promoter used for dental treatment and a method for producing the same. And a composition using an osteogenesis promoter.

[0002]

2. Description of the Related Art Recently, attempts have been made to promote bone regeneration by artificially loading a resected tooth portion with an osteogenic agent.

Further, in the field of dentistry, dental cement is used for filling root canals and bonding restorations. As this kind of dental cement, zinc phosphate, zinc / cordinol, carboxylate and the like are known.
This dental cement is used by mixing powder and liquid at the time of use, and the curing time is 4 to 10 minutes.

[0004]

As the above-mentioned bone forming agent, one containing an artificially synthesized apatite is usually used. However, this bone forming agent is extremely slow in bone formation and cannot be put to practical use. Being questioned in terms. Also, when this bone forming agent is used as a dental bone filler, apatite moves from the initial filling position, for example, enters between the gingiva and the bone, and gingiva becomes inflamed due to occlusal pressure. There is a problem that it will occur.

On the other hand, the above-mentioned dental cement shows an acidity of pH 2 to 4 when it is prepared as a paste by mixing cement powder and liquid, and when applied in the living body, it causes pulp damage. It also has the drawback of causing inflammation and not working effectively for bone formation.

The present inventors have previously proposed an osteogenesis promoter in which animal bones such as cow bones are calcinated and ground, and chitosan and a Group II metal oxide are mixed with this animal powder (Japanese Patent Application No. Hei 10-135242). 4-2
4106). It was confirmed that this osteogenesis promoter has a curing time suitable for treatment and, after curing, becomes a neutral bone formation. It was also confirmed that, when this bone formation product was used, the bone formation was remarkable as compared with the conventional osteogenesis promoter containing only apatite.

However, the above-referenced application only considers its use as a hardenable bone formation,
There is a problem that the usage is limited.

[0008] Therefore, the technical problem of the present invention is to not only promote osteogenesis and be useful for osteogenesis, but also prevent dental pulp injury and inflammation, a method for producing the same, It is to provide a composition using the same.

Another technical problem of the present invention is that it can be used not only as a hardening type bone forming material but also in a sheet form or the like, whereby it can be used for a wide range of applications. To provide the agent.

[0010]

According to the present invention, acid-soaked animal bones are calcified, neutralized, heat-extracted, concentrated and dried, and the resulting gelatin is 600-1000 ° C.
The product extracted by heating within the temperature range of
CO ₃ , Ca ₂ SiO ₄ , CaO, and Ca (OH) ₂
An osteogenesis promoting agent characterized by comprising: Here, in the present invention, the heating time at the time of heating in the temperature range of 600 to 1000 ° C. varies depending on the bone.
Time is preferred.

The product thus obtained is MgC
It has been proved that O ₃ , Ca ₂ SiO ₄ , CaO, and Ca (OH) ₂ are contained as essential components . Also, M
It may also contain gO and NaO .

Further, according to the present invention, an osteogenesis promoting composition containing the above osteogenesis promoting agent and hydroxyapatite powder can be obtained, and a curable neutral osteogenic substance can be produced.

Here, in the present invention, it is preferable that the amount of the bone formation promoter mixed is such that the weight ratio thereof to the amount of the hydroxyapatite powder is 0.05 to 35 wt%.

Furthermore, according to the present invention, an osteogenesis promoting composition containing the osteogenesis promoting agent and chitosan is obtained, and the composition can be used in the form of a sheet.

[0015]

In the present invention, a small amount of an osteogenesis promoter, chitosan sol, and hydroxyapatite are mixed,
Not only can it be used as a curable bone formation product by forming a composition, but it can also be used as an osteogenic sheet.

[0016]

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 is a diagram showing a method for extracting an osteogenesis promoting agent according to an embodiment of the present invention. As shown in Fig. 1, the bones of animals are immersed in malic acid, malonic acid, etc., and washed with water.
Leave it for 3 months and make it lime. Next, it is washed with water to remove the water-soluble substance, keratin and fat to prepare a raw material. Furthermore, this raw material is neutralized with malic acid, malonic acid, dilute hydrochloric acid, etc., washed with water, and then heated at 40 to 90 ° C. for 8 hours. In this way, the extracted extract is filtered to collect the mother liquor. The mother liquor is concentrated under reduced pressure, cooled at 10 ° C. and solidified. Gelatin is obtained by cutting the solidified product and drying at 28 ° C. The yield of this gelatin is 10 to 12% in bovine bone. Next, add gelatin to 600-1
Heated at 000 ℃ for 1-2 hours, yield 5wt as residue
A product with a pH of 12.5 was obtained in%.

In order to investigate the composition of the product thus obtained, the qualitative and content were estimated by ICP optical spectroscopy. As a result, in the product, Mg, Si,
It was found to contain S, Ca and Na. Then, by ICP optical spectroscopy, Mg, Si, S, Ca and N
The content of a was estimated. An ICP spectroscopic device (Shimadzu ICPV-1000) was used for this measurement.

More specifically, sample 0.
After heat-decomposing 2 g of hydrochloric acid and filtering, the filtrate is diluted with pure water to 50 g.
Adjusted to milliliters. The filtration residue was ashed, melted with alkali, dissolved in hydrochloric acid, and the melt was made up to 50 ml with pure water. The melt thus obtained was introduced into an ICP apparatus. Measurement result, wavelength, 383.2
3 nm (Mg), 251.61 nm (Si), 180.
73 nm (S), 317.93 nm (Ca), 589.
A peak appears at 55 nm (Na), and the product has M
It was confirmed that g, Si, S, Ca, and Na were contained. For the qualitative and content estimation by ICP optical spectroscopy, the content of the qualitative element was estimated from the ratio of the peak intensity of ICP to the background intensity. The results are shown in Table 1.

[0020]

[Table 1]

The above-mentioned Mg, Si and Ca are MgC.
Exists in O ₃ , Ca ₂ SiO ₄ , CaO, Ca (OH) ₂ .
And the product consists essentially of minerals
Can understand .

Next, it was found that the above-mentioned use example of the product has an effect of gelling chitosan sol.
Therefore, this product can be used not only as a curable bone formation product, but also as a bone formation promoting sheet by adding it to a chitosan film. First, as an example of use of this product, a case will be described in which a sheet for promoting osteogenesis is prepared by mixing the product with a chitosan film.

Example 1 Chitosan sol (chitosan.
5 g, malonic acid 0.4 g, physiological saline 8 cc) were mixed with the product 0.05 g and hydroxyapatite 1.5 g to prepare a product-containing chitosan film, that is, a bone formation promoting sheet. The curing time of this chitosan film is 1 minute 2
0 seconds, pH of cured product is 7.3, Tensile strength is 1200
It was g / cm ² and the elongation was 40%.

(Example 2) As in Example 1, 0.03 g of the product and 1.5 g of hydroxyapatite were mixed with chitosan sol (chitosan 0.5 g, malonic acid 0.4 g, physiological saline 8 cc). , The product-containing chitosan film was made. The curing time of this chitosan film is 2 minutes 50 seconds,
The cured product has a pH of 7.1 and a tensile strength of 1030 g / cm.
² and the elongation was 38%.

Example 3 As in Examples 1 and 2, 0.02 g of the product and 1.5 g of hydroxyapatite were mixed with chitosan sol (0.5 g of chitosan, 0.4 g of malonic acid, 8 cc of physiological saline). Then, I made a chitosan film. The curing time is 3 minutes 10 seconds, the pH of the cured product is 6.8,
The tensile strength was 970 g / cm ² , and the elongation was 32%.

It was found that the bone growth was promoted by applying the chitosan film of Examples 1 to 3 to the perforated bone portion.

Next, as still another example of the use of the product, the case where the product is mixed with a hardening type neutral bone forming material will be described.

(Example 4) 0.125 g of malic acid, 0.125 g of chitosan, 2 cc of physiological saline was used as chitosazol, 0.02 g of CaO, 0.02 g of ZnO, 0.4 g of hydroapatite and 0. 02 g was added to obtain a composition. The curing time of this composition is 25 seconds 29
Seconds, and the PH of this cured product was 7.7. The compressive strength of the cured composition was 14 kg / cm ² .

(Example 5) 0.125 g of malic acid, 0.125 g of chitosan, 2 cc of physiological saline was used as chitosazol, 0.02 g of CaO, 0.03 g of ZnO, 0.4 g of hydroapatite, and 0 parts of the product. 0.02 g was added to obtain a composition. The curing time of this composition was 7 minutes, and the PH of this cured product was 7.9. The compressive strength of the cured composition was 22 kg / cm ² .

(Example 6) Malonic acid 0.1 g, chitosan 0.125 g, physiological saline 2 cc to make chitosazol, CaO 0.01 g, ZnO 0.01 g, hydroapatite 0.4 g, and the product 0. 0.03 g was added to obtain a composition. The curing time of this composition was 5 minutes, and the PH of the cured product was 7.2. The compressive strength of the cured composition was 15 kg / cm ² .

Next, it was found that the above-mentioned product is effective as an osteogenesis promoter alone or by mixing with various apatites. Example 7 below describes the case where the above product was mixed with hydroxyapatite powder.

Example 7 The experimental animal weighs about 110 g.
4 weeks old SD female rat with a diameter of 2 m on the skull
It was perforated with a bone bar under water injection to a depth of 0.3 mm and a depth of 0.3 mm.
Hydroperyapatite powder alone, 0.5 g of the extract extracted according to FIG. 1, and 5 g of hydroxyapatite powder were mixed and embedded in the perforated portion. They were sacrificed 2 and 4 weeks after the operation, decalcified, and stained with Hematoxyline-eosin. As a result of observation, in the case of hydroxyapatite powder alone, no bone formation was observed in both rats for 2 weeks and 4 weeks, but in the experimental group when the product was mixed, it was young. New bone and partly mature bone,
It was confirmed that Hematoxyline-eosin was stained red.
In addition, in the 4th week rat, a considerably mature bone tissue could be confirmed.

[0033]

As is clear from the above experimental results, the product obtained by the manufacturing method of FIG. 1 is effective for the formation of new bone even if a small amount is added to apatite. This indicates that a root canal filler can be obtained by using the product alone or mixing the product with various apatites and chitosan. In addition, in the product of the present invention, high temperature heating
The product is only inorganic, not organic,
Problems such as antigen-antibody reaction and allergic reaction from an immunological point of view
Can be avoided.

Further, since the product has a property of gelling chitosan sol, a sheet for promoting bone formation can be produced, and by mixing with chitosan or the like, it can be compared with a curable neutral bone molding. It was also confirmed that the addition amounts of CaO and ZnO can be reduced. Although the case where cow bones are used has been described, the bones of animals may be bones of other animals, for example, fish bones.

[Brief description of drawings]

FIG. 1 is a diagram showing a method for extracting an osteogenesis promoting agent according to an example of the present invention.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI A61K 33/10 A61K 33/10 A61L 27/00 A61L 27/00 G A61P 19/00 A61P 19/00 (58) Fields investigated (58) Int.Cl. ⁷ , DB name) A61K 35/32 A61K 6/033 A61K 6/08 A61K 33/06-33/10 A61P 19/00 A61L 27/00

Claims (4)

(57) [Claims] 1. Bone of an acid-soaked animal is calcified,
Gelatin obtained by soaking, heat extraction, concentration and drying
Was heated and extracted within a temperature range of 600 to 1000 ° C.
A product of MgCO ₃ , Ca ₂ SiO ₄ , Ca
An osteogenesis promoter containing O and Ca (OH) ₂ . 2. The osteogenesis promoter according to claim 1,
Furthermore, an osteogenesis promoter containing at least one of MgO and NaO. 3. An osteogenesis promoting composition comprising the osteogenesis promoting agent according to claim 1 or 2 and hydroxyapatite powder. 4. A film formation promoting composition comprising the bone formation promoting agent according to claim 1 and chitosan.