JP2001293080A - Bioactive cement composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bioactive cement composition which has high bioactivity and is excellent in long-term reliability. SOLUTION: This composition comprises a bioactive filler powder in which an average size of a particle is 3 μm or lower, a methacrylate-based polymer powder, methacrylate-based monomer, polymerization intiator, polymerization accelerator and a reinforcing material.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] 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 skull defects in the field of neurosurgery, and the like. The present invention relates to a cement composition.

[0002]

2. Description of the Related Art Conventionally, PMMA cement has been used as a cement material for adhesive fixation of implant materials and filling of bone defects and reconstruction of skull defects in the field of neurosurgery, which are used in the fields of orthopedics and oral surgery. Is widely known. However, since this cement has no biological activity, it cannot be chemically bonded directly to natural bone. Therefore, in recent years, a bioactive cement to which a bioactive filler such as Ca-containing glass is added has been proposed in order to impart bioactivity to the PMMA cement.

[0003]

When the above-mentioned bioactive cement is cured in a living body, Ca ions are eluted from the filler powder exposed on the surface of the cured product and react with body fluid to form an apatite layer on the surface of the cured product. As a result, it can be chemically bonded directly to natural bone. However, at present, a bioactive cement having sufficiently high bioactivity and good workability has not yet been obtained. In addition, the Ca-containing compound releases Ca ions for a long period of time, so that the compound itself deteriorates, and the mechanical strength of the hardened cement material deteriorates. For this reason, there has not been obtained any one that does not cause deterioration in strength even when implanted in the body for a long time and has excellent long-term reliability.

An object of the present invention is to provide a bioactive cement composition having high bioactivity and excellent long-term reliability.

[0005]

The bioactive cement composition of the present invention comprises a bioactive filler powder having an average particle size of 3 μm or less, a methacrylate polymer powder, a methacrylate monomer, a polymerization initiator, a polymerization accelerator, And a reinforcing material.

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the present invention, a bioactive filler powder having an average particle size of 3 μm or less is used. The bioactivity and workability of the bioactive cement vary greatly depending on the average particle size of the bioactive filler powder and its content. That is, the average particle diameter of the bioactive filler powder is 3 μm.
m or less, the density including the filling space such as powder, so-called bulk density is reduced and the specific surface area is increased,
The bioactive filler powder is easily exposed on the surface of the hardened cement, and sufficient bioactivity can be obtained with a small amount of addition. Therefore, the content of the bioactive filler powder can be reduced, and the strength deterioration due to the deterioration of the filler powder can be significantly reduced. Further, since the resin component can be relatively increased, the workability of the cement is improved.

[0007] In particular, it is preferable that the average particle size is 0.1 to 2.6 µm, because the biological activity is further increased. However, if the average particle size exceeds 3 μm, sufficient bioactivity cannot be obtained with a small amount of use, and if the content is increased to obtain sufficient bioactivity, a rough feeling is generated at the time of kneading cement, resulting in workability. Gets worse. As the bioactive filler powder, any secondary particles having an average particle size larger than 3 μm can be used as long as they can be easily crushed and become fine powder.

As the bioactive filler powder, the calcium phosphate compound is hydroxyapatite (HAp) or β-tricalcium phosphate (β-TCP) or a complex thereof, and hydroxyapatite is particularly preferred because of its excellent biocompatibility. . As the calcium phosphate compound, an unfired powder synthesized by a liquid phase method or a crushed product of the fired product can be used. On the other hand, a preferable composition range of the Ca-containing glass or the crystallized glass powder is CaO 3 in mass%.
_{0~70%, SiO 2 30~70%,} P 2 O 5 0~40
%, MgO 0-20%, CaF ₂ 0-5%, preferably CaO 40-50%, SiO ₂ 30-40%, P ₂
O ₅ 10-20%, MgO 0.5-10%, CaF ₂
0 to 2%.

[0009] The content of the bioactive filler powder is preferably 20% by mass or less, particularly preferably 0.5 to 18% by mass. If the content of the bioactive filler powder is more than 20% by mass, the strength of the cement is likely to be deteriorated, and the workability is also deteriorated. In addition, if the bioactive filler powder is subjected to silane coupling treatment, the affinity with the methacrylate monomer is improved and the strength of the hardened cement is increased, and the powder surface has a hydrophobic group, so the blood has no inhibitory effect , The cement is easily hardened. When performing the silane coupling treatment, a weak acid to a neutral region (about pH 5 to 8)
It is preferable to carry out in. This is because if the pH is lower than 5, the glass surface is eroded to lower the biological activity, and if the pH is higher than 8, the silane coupling treatment becomes difficult.

[0010] By the way, the most important cement hardened body is
That is, it has excellent long-term reliability. Ie
Even if hardened cement is embedded in the body for a long time, strength
That is, no deterioration occurs. Therefore, in the present invention
Use reinforcement. The shape of the reinforcing material is spherical,
Although not particularly limited to scar-like, flake-like, etc.
With the use of reinforcements with morphology,
Stress concentration can be prevented.
The mechanical strength of the cured product can be improved. Also ball
Good flow with good compatibility with monomer
To obtain a cement material with good operability.
it can. The content of the reinforcing material is preferably 1 to 70% by weight, preferably
Is 10 to 60% by weight. Reinforcement content is 1 weight
%, It is difficult to obtain the effect as a reinforcing material, and
If it exceeds 70% by weight, a methacrylate-based polymer is relatively formed.
-Methacrylate monomers are not used due to less powder
It becomes difficult to polymerize and the mechanical strength decreases. Also strength deterioration
Also increases. High mechanical strength and chemical as reinforcement
Stable alumina (Al_TwoO_Three), Zirconia (Zr
O _Two), Titania (TiO_Two), Silica (SiO_Two)
use. Alumina is available in α, γ, δ, θ, and ε types.
However, any alumina can be used as reinforcement
You.

The methacrylate-based polymer powder used in the present invention is a component necessary for the polymerization of the methacrylate-based monomer, and is effectively dissolved in the monomer to form a cured product. As the polymer powder,
Polymethyl methacrylate (PMMA) is preferred,
Besides this, polyethyl methacrylate (PEMA),
A copolymer of methyl methacrylate and styrene or methacrylate or the like can be used alone or in combination of two or more.

By the way, as the polymer powder, a methacrylate polymer having a mass average molecular weight of 60,000 to 1,300,000, preferably 100,000 to 1,000,000 is used. As the mass average molecular weight of the polymer powder increases, the solubility of the polymer decreases with the monomer, and the bioactive filler is easily exposed on the cement surface, so that the bioactivity increases. The strength of the resin itself increases as the mass average molecular weight of the polymer increases. Moreover, it is considered that the dissolution in the monomer during the polymerization of the cement is stopped only on the surface, and most of the core remains in the cured product and acts as a filler, contributing to the improvement of mechanical strength. On the other hand, when a polymer having a mass average molecular weight of less than 60,000 is used, it is almost dissolved during polymerization, the bioactive filler is covered with the resin, the bioactivity is reduced, and the strength of the resin itself is low. Almost all of them are dissolved, and a sufficiently high mechanical strength cannot be obtained. The larger the weight average molecular weight of the polymer powder is, the more preferable it is. However, if the polymer exceeds 1.3 million, it is difficult to dissolve the polymer and the workability is deteriorated.

The content of the methacrylate-based polymer powder is preferably from 10 to 80% by mass. When the content is more than this, the bioactive filler powder becomes relatively small, so that the bioactivity decreases. The workability is deteriorated, and the methacrylate monomer is hardly polymerized and the mechanical strength is reduced.

The methacrylate monomer used in the present invention is a monomer which undergoes two-dimensional polymerization, and has excellent workability since the viscosity does not increase rapidly during curing. After curing, it is stable in the body for a long period of time, and the mechanical strength is not easily reduced. As methacrylate monomers, methyl methacrylate (MM
A) is most preferred, but other than this, ethyl methacrylate (EMA) or the like can be used. The content of the methacrylate monomer is preferably from 20 to 70% by mass.
When the amount of the methacrylate-based monomer is less than 20% by mass, the polymerization becomes difficult, and the mechanical strength is reduced. When the amount is more than 70% by mass, the biological activity is reduced.

In addition to methacrylate monomers, dimethacrylate monomers can be added. The dimethacrylate-based monomer is a monomer which is polymerized three-dimensionally to become a high-strength polymer, and is stable in the body for a long time after curing, and is unlikely to have low mechanical strength.
As dimethacrylate monomers, 2,2-bis [4
-(3-methacryloxy-2-hydroxypropoxy)
Phenyl] propane (Bis-GMA), 2,2-bis (4-methacryloxyethoxyphenyl) propane (B
is-MEPP), triethylene glycol dimethacrylate (TEGDMA), diethylene glycol dimethacrylate (DEGDMA), ethylene glycol dimethacrylate (EGDMA), and the like.

The powder-liquid ratio of the powder component composed of the bioactive filler powder, the methacrylate-based polymer powder, the reinforcing material, and the like to the liquid component composed of the methacrylate-based monomer or the dimethacrylate-based monomer is as follows:
It is desirable that the ratio be 0:70 to 90:10.

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 8 with respect to 100 parts by mass of the powder component.
If the amount is less than 0.1 part by mass, there is almost no effect. If the amount is more than 8 parts by mass, the curing time is too fast, and the workability tends to deteriorate. 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 8 with respect to 100 parts by mass of the liquid component.
Parts by weight are preferred. When the amount of the polymerization accelerator is less than 0.1 part by mass, the monomer is not cured unless heated to 100 ° C. or more when polymerizing the monomer, so that it cannot be used in actual surgery.
On the other hand, if the amount is more than 8 parts by mass, the curing time becomes too fast, and the workability is likely to deteriorate. In addition, N, N
Tertiary amines such as -dimethyl-P-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 drug, a bone formation factor, a polymerization inhibitor, a polymerization inhibitor, and an antioxidant 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.

In the bioactive cement composition of the present invention provided in a powder-liquid system, a polymerization reaction occurs when the powder and the liquid are mixed, and the curing is completed in about 3 to 15 minutes. The cement can be freely shaped into a desired shape within the time until hardening.

[0023]

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 8) and Table 3 show comparative examples (sample Nos. 9 to 12).

[0024]

[Table 1]

[0025]

[Table 2]

[0026]

[Table 3]

Each sample was prepared as follows.

First, hydroxyapatite powder, Ca-containing glass powder, Ca-containing crystallized glass powder, methacrylate-based polymer powder, and reinforcing material powder having the average particle sizes shown in the table were prepared.

As the hydroxyapatite powder, an unfired powder synthesized by a liquid phase method and this powder
What was baked at ℃ was used.

As a Ca-containing glass powder, C is expressed in terms of% by weight.
aO 45%, SiO ₂ 34%, P ₂ O ₅ 16%, M
A glass having a composition of 4.5% gO and 0.5% CaF ₂ is melted and then pulverized, and the pulverized glass powder is used as the Ca-containing crystallized glass powder.
A material that had been crystallized by heat treatment at 50 ° C. for 5 hours was used.

These powders were subjected to a surface treatment using a silane coupling agent adjusted to pH 6.

As the methacrylate polymer powder,
A PMMA powder having a mass average molecular weight of 300,000 was prepared.

As the reinforcing material, α-alumina, δ-alumina, zirconia, titania, and silica were prepared.

Next, two types of hydroxyapatite powder, Ca-containing glass powder, Ca-containing crystallized glass powder,
The methacrylate polymer powder and the reinforcing material powder were weighed at the ratios shown in the table, and benzoyl peroxide was added as a polymerization initiator and mixed.

As the methacrylate monomer, M
MA was prepared, and N, N-dimethyl-p-toluidine was added as a polymerization accelerator, followed by stirring.

Thus, a powder-liquid sample was obtained.

The amounts of benzoyl peroxide and N, N-dimethyl-p-toluidine were set to 3 parts by mass and 1 part by mass, respectively, with respect to 100 parts by mass of the total amount of the monomers so as to cure in about 7 minutes. .

The samples prepared by the above procedure were evaluated for the average particle size of the bioactive filler powder, the presence or absence of bonding with the surrounding bone, workability, and bending strength. Tables 1 to 3 show these results.

The average particle diameter of the bioactive filler powder was measured by a laser diffraction type particle size distribution analyzer and expressed as a _D50 value. After the sample was implanted into the tibial cavity of the rat, the implanted site was taken out 8 weeks after the sample was implanted into the tibial cavity of the rat. The above evaluation was evaluated as "O", and the evaluation of less than 30% of the entire circumference of the sample was evaluated as "X". The workability evaluated the ease of work when kneading the cement by hand. The bending strength is
A sample of 3 × 4 × 20 mm in size was prepared from the hardened cement, the initial strength was measured by a three-point bending strength test, and the strength of the sample after immersion in physiological saline at 37 ° C. for 6 months was also measured. Was done.

As is clear from the table, the No. 1 embodiment according to the present invention is the same as the embodiment shown in FIG. Regarding the samples Nos. 1 to 8, the average particle diameter of the bioactive filler powder was 0.5 to 1.5 μm, the bond with the surrounding bone was recognized, and the workability was good. In addition, the initial strength was 125 MPa or more, and No. The strength was higher at about 30 to 40 MPa than that of No. 10, and there was almost no deterioration in strength with time.

On the other hand, the sample No. 9, although the content of the bioactive filler powder is the same as in the example,
Bonding to surrounding bone was insufficient due to the large average particle size. Sample No. Sample No. 10 did not contain a reinforcing material, and thus had a low initial strength and a large temporal change in strength.

[0042]

As described above, the bioactive cement composition of the present invention is directly bonded to natural bone and hardly deteriorates with time as compared with a conventional bioactive cement. Furthermore, even if the content of the bioactive filler is small, sufficient bioactivity is exhibited. For this reason, the amount of resin can be increased by reducing the amount of filler powder, and it is possible to obtain a cement with less strength deterioration and good workability. Therefore, the bioactive cement composition of the present invention is suitable for adhesive fixation of implant materials, filling of bone defects, reconstruction of skull defects, etc. in the fields of orthopedic surgery, neurosurgery, and oral surgery. It is.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Seiichi Morita 2-7-1 Hararashi, Otsu City, Shiga Prefecture Nippon Electric Glass Co., Ltd. F-term (reference) 4C081 AB04 AB06 AC04 CA081 CE11 CF012 CF122 CF132 CF142 CF152 DA11 DA15 4C089 AA10 BA04 BA05 BA06 BA12 BA13 BA16 BC06 BC08 BD01 BE03 CA02 CA03 CA06

Claims (4)

[Claims] 1. A bioactive filler powder having an average particle diameter of 3 μm or less, a methacrylate polymer powder, a methacrylate monomer, a polymerization initiator, a polymerization accelerator,
A bioactive cement composition comprising a reinforcing material. 2. The bioactive cement composition according to claim 1, wherein the bioactive filler powder is a glass or crystallized glass containing a calcium phosphate compound or Ca. 3. The content of the bioactive filler powder is 20
The bioactive cement composition according to claim 1, wherein the content is not more than mass%. 4. The bioactive cement composition according to claim 1, wherein the reinforcing material comprises one or more of alumina, zirconia, titania and silica.