JPH10234841A - Boiactive cement composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enable direct connection to a natural bone while preventing deterioration in mechanical characteristic during the prolonged burial by arranging alumina powder containing a δ-Al2 O3 crystal, a δ-Al2 O3 crystal or amorphous alumina, polymethyl methacrylate powder, a methacrylate based monomer, a polymerization initiator and a polymerization promotor. SOLUTION: Alumina powder with a crystal structure of α-Al2 O3 undergoes a melting treatment in a flame above 2,000 deg.C to obtain alumina powder containing δ-Al2 O3 crystal, γ-Al2 O3 crystal and amorphous alumina. This powder is blended with polymethyl methacrylate powder, glass powder containing Ca and benzoyl peroxide as polymerization initiator. Moreover, a dimethacrylate based monomer and demethyl-p-toluidine are added and kneaded to obtain a bioactive cement composition component. This composition component causes no drop in the bending strength in about six months after burying in vivo and operability is also better.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to bioactivity used for adhesive fixation of implant materials used in the fields of orthopedics and oral surgery, filling of bone defects, reconstruction of cranial defects in neurosurgery, and the like. The present invention relates to a cement composition.

[0002]

2. Description of the Related Art Conventionally, natural bone is used as a cement material for adhesive fixation of implant materials used in orthopedic surgery and oral surgery, filling of bone defects, reconstruction of cranial defects in neurosurgery, and the like. Bioactive cements have been proposed that combine directly with the cement. For example, a cement comprising a Ca-containing inorganic material powder (apatite, Ca-containing glass, etc.) and a dimethacrylate-based monomer (Bis-GMA, etc.) has been proposed. When this bioactive cement is cured in a living body, Ca ions are eluted from the Ca-containing inorganic material powder exposed on the surface of the cured body, and react with body fluid to form an apatite layer on the surface of the cured body. Can be combined.

[0003]

However, in the above cement, since the Ca-containing inorganic material powder continuously releases Ca ions for a long period of time, the powder itself deteriorates, and the mechanical properties of the hardened cement become poor. It decreases significantly. In addition, there is a disadvantage that molding is difficult due to rapid curing, and operability is not very good.

[0004] It is an object of the present invention to provide a bioactive cement which can be directly bonded to natural bone, has low mechanical properties even when implanted in a living body for a long time, and has good operability. It is to be.

[0005]

The bioactive cement composition of the present invention comprises an alumina powder, a polymethyl methacrylate powder, a methacrylate monomer, a polymerization initiator and a polymerization accelerator, and the alumina powder contains at least δ-Al ₂
It is characterized by containing O ₃ crystal, γ-Al ₂ O ₃ crystal or amorphous alumina.

In the present invention, alumina powder, which is one of the powder components, is different from alumina powder having no biological activity which has been widely used conventionally. That is, the conventional alumina powder has a stable α-Al ₂ O ₃ crystal structure, but the alumina powder used in the present invention has at least δ-Al ₂ O ₃ crystal and γ-Al ₂ O ₃ crystal. Or active alumina in which amorphous alumina exists. From the viewpoint of bioactivity, δ-Al ₂ O ₃ crystals in alumina powder, γ
It is desirable that the proportion of the Al ₂ O ₃ crystal and the non-crystalline alumina is 30% by weight or more. The smaller the alumina powder is, the higher the strength of the cement can be obtained. Specifically, the alumina powder is preferably 10 μm or less. Also, if the surface is subjected to silane coupling treatment, familiarity with the dimethacrylate monomer is improved, the strength of the cement hardened body is increased, and the powder surface has a hydrophobic group, so there is no blood inhibition, The cement hardens. The alumina powder is preferably spherical. The content of the alumina powder is 30 to
Preferably it is 90% by weight.

The above alumina powder can be produced as follows. First, a normal alumina powder having a crystal structure of α-Al ₂ O ₃ is prepared. The alumina powder has an average particle diameter D ₅₀ to use those of 10μm or less. Then
Alumina powder at 1500 ° C or higher, preferably 2000 ° C
After rapid heating, melting and vitrification, rapid cooling is performed. Thus, at least δ-Al ₂ O ₃ crystal, γ-Al
A chemically unstable, ie, bioactive, alumina powder containing ₂ O ₃ crystalline or amorphous alumina can be obtained. Note The particle size of the alumina powder was 10μm or less, tends to precipitate is rapidly heated quenching becomes difficult stable α-Al ₂ O ₃ When the particle size increases, more than 10μm when alpha-Al ₂ O ₃ The amount of crystal precipitation accounts for 30% by weight or more,
This is because the alumina powder is chemically stable, that is, has low bioactivity.

The polymethacrylate-based powder is a component necessary for the polymerization of the methacrylate-based monomer, and its content is preferably 10 to 70% by weight of the powder component. (Or, further, Ca-containing inorganic material powder) is reduced, so that the biological activity is reduced. Conversely, if the content is too small, the handleability is deteriorated and the methacrylate monomer is hardly polymerized. Note that polymethyl methacrylate (PMMA) powder can be used as the polymethacrylate-based powder.

In the present invention, for example, a Ca-containing inorganic material powder can be contained as a powder component in addition to the above. Ca-containing inorganic material powder is a component added to improve the adhesion to natural bone at the initial stage of implantation and to enable early bonding, such as Ca-containing glass, crystallized glass, and calcium phosphate compound. , Calcium carbonate and the like can be used. In particular, Ca-containing glass and crystallized glass elute Ca ions in vivo and exhibit high bioactivity. As such glass, in particular CaO 30 to 70% by weight percent, SiO ₂ 30 to 70
_{%, P 2 O 5 0~40%} , 0~20% MgO, Ca
F ₂ 0 to 5%, in particular CaO 40~50%, SiO _{2
30~40%, P 2 O 5 10~20} %, MgO 0
10%, the glass or crystallized glass having a composition of CaF ₂ 0 to 2% is preferred. The calcium phosphate compounds include CaHPO ₄ , Ca ₃ (PO ₄ ) ₂ , Ca ₅
(PO ₄ ) ₃ OH, CaP ₄ O ₁₁ , Ca (PO ₃ ) ₂ ,
Ca ₂ P ₂ O ₇ , Ca ₄ O (PO ₄ ) ₂ , Ca ₁₀ (PO
₄ ) ₆ (OH) ₂ , Ca (H ₂ PO ₄ ) ₂ .H ₂ O or the like as a main component. The Ca-containing inorganic material powder is preferably spherical. When the Ca-containing inorganic material powder is contained, the proportion of the powder component is 5 to 7%.
It is desirably in the range of 5% by weight.

In the present invention, the methacrylate monomer, which is a liquid component, is a monomer that undergoes two-dimensional polymerization. Although the initial strength is not as high as that of the dimethacrylate monomer, the viscosity gradually increases during curing, so that operability is increased. Excellent. After the curing, it is stable in the body for a long period of time, and the mechanical strength is not easily reduced. As the methacrylate-based monomer, methyl methacrylate (MMA), which is currently used in the field of orthopedic surgery, is most preferable, but ethyl methacrylate and the like can also be used.

In addition to methacrylate monomers, dimethacrylate monomers can be added. A dimethacrylate monomer is a monomer that is polymerized three-dimensionally to become a high-strength polymer, and after curing, is stable in the body for a long period of time, and is unlikely to have low mechanical strength.
In addition, there is an effect that an unpolymerized layer is formed on the surface of the cured product and the body fluid permeates into the interior of the cured product. As a result, not only the alumina powder (or further Ca-containing inorganic material powder) exposed on the surface of the cured body, but also the alumina powder (or further Ca-containing inorganic material powder) buried inside shows bioactivity. Becomes possible. As the dimethacrylate-based monomer, 2,2-bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane (Bis-GMA) is preferable.
-Bis (4-methacryloxyethoxyphenyl) propane (Bis-MEPP), triethylene glycol dimethacrylate (TEGDMA), diethylene glycol dimethacrylate (DEGDMA), ethylene glycol dimethacrylate (EGDMA), and the like can be used. Since monomers such as TEGDMA, DEGDMA, and EGDMA have low viscosity, they can be used as diluents when the viscosity is too high to handle easily.

A powder component comprising alumina powder, polymethacrylate powder, Ca-containing inorganic material powder and the like,
The powder-liquid ratio of the liquid component composed of a methacrylate-based monomer or a dimethacrylate-based monomer is desirably 50:50 to 90:10 in a weight ratio of powder: liquid.

Further, the bioactive cement composition of the present invention contains a polymerization initiator and a polymerization accelerator.

The polymerization initiator is used by adding to the powder component. The addition amount is 0.1 to 2 with respect to 100 parts by weight of the powder component.
If the amount is less than 0.1 part by weight, there is almost no effect. If the amount is more than 2 parts by weight, the curing time is too fast and the workability is deteriorated. In addition, as a polymerization initiator, benzoyl peroxide, tri-n-butylborane, or the like can be used.

The polymerization accelerator is used by adding it to the liquid component. The addition amount is 0.1 to 2 with respect to 100 parts by weight of the monomer.
Parts by weight. If the amount of the polymerization accelerator is less than 0.1 part by weight, the monomer will not be cured unless heated to 100 ° C. or more when polymerizing the monomer, so that it cannot be used in an actual operation site. On the other hand, if the amount is more than 2 parts by weight, the curing time becomes too fast and the workability deteriorates. In addition, dimethyl-P-
Tertiary amines such as toluidine can be used.

Further, the bioactive cement composition of the present invention comprises
In addition to the above components, various components such as a fused silica powder, colloidal silica, a drug, a bone forming factor, and a polymerization inhibitor can be added as necessary.

The form of providing the bioactive cement composition of the present invention is a powder-liquid system, and the user may use a mixture of powder and liquid.

[0018]

The bioactive cement composition of the present invention, which is provided in a powder-liquid system, undergoes a polymerization reaction when the powder and the liquid are mixed, and the curing is completed in about 3 to 15 minutes. Because of the inclusion, the change in viscosity during polymerization occurs more slowly than in the case of dimethacrylate monomer alone. Therefore, the operability is good, and a desired shape can be freely formed within the time until curing.

Also, since it contains a special alumina powder capable of inducing natural bone, it can be combined with natural bone. In addition, since this alumina powder does not release ions in a living body, the powder does not deteriorate and the strength is hardly reduced.

When a dimethacrylate-based monomer is further contained, an unpolymerized layer is formed on the surface of the cured product, and a body fluid penetrates into the cured product, so that alumina powder (or further Ca-containing inorganic material powder) buried therein is used. Can also come into contact with bodily fluids and can be connected to surrounding bone in a short time.

[0021]

The present invention will be described below in detail based on examples and comparative examples.

Tables 1 and 2 show examples of the present invention (sample N
o. 1 to 6) and Comparative Examples (Sample Nos. 7 and 8).

[0023]

[Table 1]

[0024]

[Table 2]

[Preparation of Sample] 1 to 6 were prepared as follows.

First, alumina powder, polymethacrylate powder and Ca-containing inorganic material powder were prepared.

The alumina powder was produced as follows.
First, a normal alumina powder (average particle size: 10 μm) having a crystal structure of α-Al ₂ O ₃ was prepared. Next, this powder is supplied into a flame of 2000 ° C. or more, blown away while melting, and then quenched in water to obtain δ-Al ₂ O.
_An alumina powder containing _three crystals, γ-Al ₂ O ₃ crystal and amorphous alumina was obtained. The alumina powder thus obtained was spherical due to surface tension. As a result of X-ray diffraction, α-Al ₂ O ₃ crystals were further contained in the powder, but the content was about 5 to 10% by weight. Further, the surface of the alumina powder was subjected to a coupling treatment.

Examples of the polymethacrylate powder include PM
MA powder (particle diameter 30 μm, average molecular weight 130,000) was prepared.

As the Ca-containing inorganic material powder, 46.7% by weight of CaO, 35.6% by weight of SiO ₂ , P ₂ O ₅
A spherical Ca-containing glass powder having a composition of 17.0% and CaF _{2 of} 0.7% and an average particle diameter of 4 μm was used.

Next, alumina powder, PMMA powder and Ca
The contained glass powder was weighed at the ratio shown in the table, and benzoyl peroxide was added as a polymerization initiator and mixed.

As the methacrylate monomer, M
MA is used as a dimethacrylate monomer as Bis-G
MA and TEGDMA were prepared.

Next, MMA, Bis-GMA and TEG
DMA was weighed at the ratio shown in the table, and dimethyl-p-toluidine was added as a polymerization accelerator and kneaded.

Thus, a powder-liquid type sample was obtained.

Sample No. 7 was prepared as follows.

First, a Ca-containing glass powder, Bis-GMA, TEGDMA, benzoyl peroxide and dimethyl-p-toluidine were prepared in the same manner as described above. Then Ca
Mixed glass containing benzoyl peroxide and Bis-
GMA, TEGDMA and dimethyl-p-toluidine were kneaded to obtain a powder-liquid sample.

Sample No. 8 used a commercially available PMMA cement.

The composition ratio of the powder and the monomer, and the powder-liquid ratio were each represented by weight ratio. The amounts of benzoyl peroxide and dimethyl-p-toluidine were set to 2 parts by weight and 1.4 parts by weight, respectively, based on 100 parts by weight of the total amount of the monomers so as to cure in about 7 minutes.

[Evaluation] Subsequently, the bending strength of each sample at the initial stage and at six months after implantation in a living body, the bonding time with surrounding bone, and operability were evaluated.

As is clear from Table 2, the sample No. In No. 7, bonding to the surrounding bone was observed after 2 weeks, but the initial strength was 110 MPa, and 6 months after implantation in the living body, the bending strength was significantly reduced, and was 35 MPa. The operability was not so good either. Sample No. In No. 8, the operability was good, the initial strength was 95 MPa, and after 6 months, the bending strength was small at 80 MPa, but the initial strength was insufficient. Moreover, no connection with the surrounding bone was observed.

On the other hand, in the embodiment of the present invention, No. 1-6
It was found that the sample had an initial strength of 110 MPa or more, and 85 MPa or more at 6 months after implantation in a living body, had sufficient bending strength, and was hardly deteriorated in strength. In addition, the connection with the surrounding bone was recognized, and the operability was good.

The bending strength was evaluated by a three-point bending test. Each sample was kneaded and hardened, and 3 × 4 × 20
A sample of mm was prepared and its initial strength was measured. After the specimen was implanted subcutaneously in a rat, it was taken out and measured after 6 months. Regarding the timing of connection with the surrounding bone, after implanting the sample into the tibial cavity of the rat, the implantation site is periodically removed to evaluate whether there is a part where the sample and the natural bone are directly connected. did. This was confirmed by observing the surface of the embedded specimen with an electron microscope and conducting EPMA line analysis.

[0042]

As described above, the bioactive cement composition of the present invention can directly bond to natural bone and can maintain practically sufficient mechanical strength for a long period of time.
Moreover, the operability is good. Therefore, it is suitable for bonding and fixing an implant material, filling a bone defect, reconstructing a cranial defect, and the like in the fields of the orthopedic field, the neurosurgery field, the oral surgery field, and the like.

Claims (9)

[Claims] An alumina powder, a polymethacrylate-based powder, a methacrylate-based monomer, a polymerization initiator and a polymerization accelerator, wherein the alumina powder has at least δ-Al ₂ O
_A bioactive cement composition comprising _three crystals, γ-Al ₂ O ₃ crystal or amorphous alumina. 2. The method according to claim 1, wherein the polymethacrylate-based powder is a polymethyl methacrylate powder.
Bioactive cement composition. 3. The bioactive cement composition according to claim 1, wherein the methacrylate monomer is methyl methacrylate. 4. The bioactive cement composition according to claim 1, wherein a dimethacrylate monomer is added. 5. The method according to claim 1, wherein the dimethacrylate monomer is 2,2.
The bioactive cement composition according to claim 4, wherein the composition is bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane. 6. The bioactive cement composition according to claim 1, wherein the polymerization initiator is benzoyl peroxide. 7. The bioactive cement composition according to claim 1, wherein the polymerization accelerator is dimethyl-p-toluidine. 8. The bioactive cement composition according to claim 1, wherein a Ca-containing inorganic material powder is added. 9. The bioactive cement composition according to claim 1, wherein the composition is provided in a powder-liquid system.