JPH06245990A - Bioactive cement - Google Patents

Abstract

PURPOSE:To provide a bioactive cement which can adhesively bond and fix an artificial biomaterial by self-curing in an early period, is chemically bound to the viable bone, has stability over a long period of time within the living body and is not deteriorated in mechanical strength. CONSTITUTION:This bioactive cement consists of a filler composed of non- alkaline glass powder contg. Ca, a monomer contg. dimethacrylate having hydrophilicity, a polymn. initiator and a polymn. accelerator. The bioactive cement has a property to from a hydroxyl apatite layer on the surface when the cured body thereof comes into contact with the body fluid.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bioactive cement used for fixing implant materials used in the fields of orthopedics and dentistry.

[0002]

2. Description of the Related Art In the field of orthopedic surgery, a bone may be partially lost due to a fracture or a bone tumor, and a part of the bone may be removed by surgery. On the other hand, in the field of dentistry, a jaw bone may be damaged due to tooth extraction or alveolar pyorrhea. In these cases, an implant material made of metal, ceramics, crystallized glass or the like is used in order to repair the missing or excised part.

It is desirable that such an implant material be embedded and fixed in the repaired portion at an early stage and with good compatibility. For this purpose, it is necessary to grind or process the implant material according to the shape of the repaired portion. However, it is very difficult to perform such grinding and processing accurately.

Therefore, when such an implant material is used, a biomedical cement is generally used to bond and fix the implant material and the living bone. As such a biomedical cement, for example, polymethylmethacrylate (PMMA) cement is widely used in the field of orthopedics. In the dental field, zinc phosphate cement and carboxylate cement are used.

The above-mentioned various types of biomedical cement can be firmly bonded to the implant material. However, there is a risk that these biocement cements may be loosened between the biomedical cements and living bones, or may cause an inflammatory reaction in surrounding tissues.

Under these circumstances, various kinds of biocement have been proposed in which a bioactive material is added as a filler so as to be chemically bonded to a living bone. For example, Japanese Patent Publication Sho 5
4-42384 includes polymethylmethacrylate (P
_{K 2 O-Na 2 O-} CaO-MgO in MMA) Cement
Cement comprising adding -SiO ₂ -P ₂ O ₅ based crystallized glass powder is disclosed.

[0007] In addition, in Japanese Patent Publication No. 62-503148,
2,2-bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane (hereinafter Bis-
A cement comprising a monomer based on GMA) and an apatite powder, or optionally a bioglass powder, is disclosed.

[0008]

However, the conventional biomedical cement as described above has a degree of bonding with living bone, a bonding strength, a strength of the hardened cement itself after hardening and / or a chemical composition of the hardened body. In terms of stability, etc., it was not yet sufficiently satisfactory.

For example, the biomedical cement disclosed in Japanese Examined Patent Publication No. 54-42384 has a drawback in that the bond strength with living bone is not sufficient. The present inventors have investigated the cause, and when the cement hardens, cerebrospinal fluid inside the hardened body,
This was because the crystallized glass powder could not exhibit bioactivity because body fluids such as lymph and saliva did not enter. Further, it was also found that this is because the monomer (methyl methacrylate, hereinafter referred to as MMA) has almost no hydrophilicity.

In addition to the above, the MMA undergoes linear polymerization, so that the strength of the cured product itself becomes low.

Furthermore, the crystallized glass used as a filler in the cement for living body disclosed in Japanese Patent Publication No. 54-42384 has a chemical content because it contains an alkaline component such as Na ₂ O or K ₂ O. The durability was not good, and the bioactivity was insufficient.

On the other hand, Bis-GMA, which is used as a curing agent in the biomedical cement disclosed in Japanese Patent Publication No. 62-50314, has high hydrophilicity. Therefore, according to the above-mentioned knowledge of the present invention, this cement for living organisms is one in which body fluid easily penetrates into the hardened body and should be able to chemically bond to living bones. However, as a result of examination by the present inventors, sufficient bond strength was not obtained. This is because the bioactivity of the apatite used as a filler by this biocement is low,
This is because when the apatite powder is used alone, the bonding speed with the living bone is slow and the bonding strength is weak. In addition, when the bioglass powder is used in combination, the binding rate with the living bone is increased, but the Na content in the glass is increased.
_{Since 2} O easily elutes, a thick and fragile silica gel layer is formed on the surface of the bioglass powder, and as a result, it becomes difficult to firmly bond with the living bone. In addition, since bioglass has low chemical durability, the pH of the body fluid may increase due to the eluted Na ⁺ ions, which may adversely affect the surrounding tissues. Further, if it is embedded in a body fluid for a long period of time, the glass powder will collapse, resulting in a problem that the hardened cement itself deteriorates in strength.

The object of the present invention is that it can self-cure early to bond and fix artificial biomaterials, and that it can chemically bond to living bones and is stable in the living body for a long period of time. And to provide a bioactive cement that does not deteriorate in mechanical strength.

[0014]

Means for Solving the Problems As a result of various studies, the present inventors have combined an alkali-free glass powder and / or a crystallized glass powder containing Ca with a dimethacrylate having hydrophilicity. It was found that the above-mentioned object can be achieved.

That is, the bioactive cement of the present invention is Ca
A non-alkali glass powder and / or a filler consisting of crystallized glass powder, a monomer containing a hydrophilic dimethacrylate, a polymerization initiator, and a polymerization accelerator, when the cured product comes into contact with body fluid, It is characterized by having a property of forming a hydroxyapatite layer on the surface.

The alkali-free glass powder and the crystallized glass powder containing Ca need to be capable of eluting Ca ²⁺ ions in the living body. Therefore, a glass powder having a composition of CaO 20-60% by weight, SiO ₂ 20-50% by weight, P ₂ O ₅ 0-30% by weight, MgO 0-20% by weight, CaF ₂ 0-5% by weight, and Crystallized glass powder, especially CaO 40-5 by weight percentage
0% by weight, SiO ₂ 30-40% by weight, P ₂ O ₅ 10
-20% by weight, MgO 0-10% by weight, CaF ₂ 0
It is desirable to use glass powder or crystallized glass powder with -2%.

The reason why the glass composition is limited as described above is as follows. When CaO is less than 20%, Ca ²⁺ ions are difficult to elute and bioactivity is lowered, and when it is more than 60%, chemical durability is lowered. If the SiO ₂ content is less than 20%, the chemical durability will decrease, and if it exceeds 50%, it will be difficult to obtain a homogeneous glass. P ₂ O ₅ is 30% and MgO is 2
If it is more than 0%, the chemical durability decreases. Ca
When F ₂ is more than 5%, devitrification becomes remarkable and it becomes difficult to obtain a homogeneous glass.

Further, in order to obtain a high-strength cement hardened product and to obtain high bioactivity, it is preferable that the particle size of the glass powder or the crystallized glass powder is small, specifically, 6
It is preferably 5 μm or less.

The reason why the glass powder and the crystallized glass powder are limited to those containing no alkali component is as follows.
That is, if the glass powder or the crystallized glass powder contains an alkaline component, the chemical durability of the glass will be significantly reduced, and the glass will collapse during implantation in the living body for a long period of time.
As a result, the strength of the hardened cement itself is also deteriorated. In addition, the eluted alkaline component may raise the pH of the body fluid, which may adversely affect the surrounding tissues. In addition, as a result of containing an alkaline component, this elutes to form a thick and brittle silica gel layer on the surface of the glass powder,
The inconvenience of not being able to firmly bond with living bone occurs.

The surface of the glass powder or crystallized glass powder is preferably subjected to a silane coupling treatment because the bond with the polymer can be strengthened. Examples of silane coupling agents that can be used for this purpose include 3-methacryloxypropyltrimethoxysilane, 3-aminoethylaminopropyltrimethoxysilane, and 3-glycidoxypropyltrimethoxysilane.

The monomer used in the present invention includes hydrophilic ditacrylate. Dimethacrylate is a polyfunctional monomer, and when it is polymerized, it undergoes cross-linking polymerization, resulting in a polymer having very high mechanical strength. In addition,
The hydrophilic monomer means, for example, a monomer having a hydrophilic group such as an OH group so that body fluid can easily enter the inside of the material. Bis-GMA is mentioned as a suitable example of the dimethacrylate which has such hydrophilicity. Bis-GMA is a preferable monomer as a biomaterial because it is easily available and is not harmful to living organisms. However, as described above, a monomer other than Bis-GMA may be used as long as it has a hydrophilic group such as an OH group and can allow a body fluid to easily enter the inside of the material.

In addition to the above-mentioned hydrophilic dimethacrylate, other monomers may be contained if necessary.
When the above Bis-GMA is used alone, it may be difficult to handle due to its high viscosity. Therefore, for example, triethylene glycol dimethacrylate (TEGDM
A), diethylene glycol dimethacrylate (DEG
DMA), ethylene glycol dimethacrylate (EG
It is preferable to use a monomer such as DMA) together. Further, if necessary, a monomer having almost no hydrophilicity may be contained. Using a monomer that has almost no hydrophilicity,
This is to control the hydrophilicity of the surface of the hardened cement. As such a control agent, specifically,
2,2-bis (4-methacryloxyphenyl) propane (BPDMA), 2,2-bis (4-methacryloxyethoxyphenyl) propane (Bis-MEPP), and 2,2-bis (4-methacryloxypolyethoxy) Phenyl) propane (Bis-MPEPP) and the like.

The glass powder and the crystallized glass powder may be mixed with the monomer at any ratio. However, in terms of workability such as cement kneading, the mixing ratio of the powder and the monomer is preferably in the range of 30:70 to 90:10 by weight.

As the polymerization initiator, benzoyl peroxide, tri-n-butylborane or the like can be used. It is also possible to cure by photopolymerization by using a sensitizer such as dl-camphorquinone.
Although various forms of including these polymerization initiators are possible, the addition amount thereof is appropriately 0.01 to 2% by weight based on 100% by weight of the entire cement. The amount added is 0.0
This is because if it is less than 1% by weight, the polymerization reaction does not proceed and the curing time becomes long and the workability of kneading the cement deteriorates. On the other hand, if it is more than 2% by weight, the polymerization reaction of the monomer will occur rapidly, so that the curing time will be too short and the workability of kneading the cement will also deteriorate.

As the polymerization accelerator, it is possible to use tertiary amines such as dimethyl-p-toluidine, diethyl-p-toluidine and dimethylaniline. There are various possible forms containing these polymerization accelerators, but the addition amount is 0.01-2 based on 100% by weight of the entire cement.
Weight percent is suitable. If the amount of the polymerization accelerator is less than 0.01% by weight, the polymerization reaction will not proceed and the curing time will increase.
This is because, as in the case of the above-mentioned polymerization initiator, the workability of kneading cement decreases. On the other hand, if it is more than 2% by weight, the polymerization reaction of the monomer will occur rapidly, and the curing time will be too short, and the workability of kneading the cement will also deteriorate.

In the form in which the bioactive cement of the present invention is provided to the user, powder-liquid system (powder system is glass powder or crystallized glass powder and polymerization initiator, liquid system is monomer and polymerization accelerator). Alternatively, there are two paste systems (one paste is glass powder or crystallized glass powder and monomer and polymerization initiator, and the other is glass powder or crystallized glass powder, monomer and polymerization accelerator). The user uses the powder and the liquid in each form or the two pastes mixed with one another. What kind of provision form should be decided in consideration of various conditions. Generally, when the amount of powder is large, the workability of kneading the powder and the curing liquid becomes poor. Therefore, it is preferable to provide two pastes in advance. In the case of the bioactive cement of the present invention, it has been proved that the two-paste system is desirable when the powder amount is 80% by weight or more.

[0027]

When a filler composed of non-alikari glass powder containing Ca and / or crystallized glass powder, a monomer containing hydrophilic dimethacrylate, a polymerization initiator and a polymerization accelerator are mixed in appropriate proportions, A polymerization reaction occurs and the resin is cured in a short time of about 3-15 minutes.

As a result, a hardened cement product having high mechanical strength can be obtained.

This cement-hardened product is a Ca powder from a glass powder or crystallized glass due to water entering from the surface of the hardened product.
^{Elute 2+} ions. The eluted Ca ²⁺ ions react with PO ^4- ions in the body fluid, and as a result, a hydroxyapatite layer similar to the components of living bone is formed on the surface of the hardened body. This allows
The hardened cement can be firmly and easily bonded to living bone. Further, since there is no elution of alkali ions such as Na ⁺ ions, a thick and brittle silica gel layer cannot be formed on the surface.
Therefore, the binding force with the living bone does not decrease.

[0030]

EXAMPLES The bioactive cement of the present invention will be described below based on examples.

Tables 1 and 2 show examples of the present invention (Sample N).
o. 1 to 16) and Table 3 shows a comparative example (Sample No. 17).
~ 24) respectively.

[0032]

[Table 1]

[0033]

[Table 2]

[0034]

[Table 3]

Each sample was prepared as follows.

First, CaO 44.7% by weight,
MgO 4.6%, SiO ₂ 34.0%, P ₂ O ₅
Raw materials prepared to have a composition of 16.2% and CaF ₂ 0.5% were melted and vitrified at 1500 ° C. for 2 hours, and then roll-formed. Next, this glass molded body was crushed by a ball mill and then classified to obtain glass powder having a maximum particle size of 65 μm or less. Further, the glass molded body produced in the same manner as above was crystallized by firing at 1050 ° C. for 4 hours, then crushed by a ball mill and classified to obtain a crystallized glass powder having a maximum particle size of 65 μm. Furthermore, these glass powders and crystallized glass powders were respectively put into an acetic acid aqueous solution containing 1% by weight of 3-methacryloxypropyltrimethoxysilane, heated and stirred, and then dried at 120 ° C. for 2 hours to perform a silane coupling treatment. The applied glass powder A and crystallized glass powder A were obtained.

Further, in the same manner as above, Ca by weight percentage is
O 46.5%, SiO ₂ 36.0%, P ₂ O ₅ 1
A glass powder B and a crystallized glass powder B having a composition of 7.0% and CaF ₂ 0.5% and subjected to a silane coupling treatment were obtained.

In addition, the weight percentage of Na ₂ O 25.0
%, CaO 25.0%, SiO ₂ 45.0%, P ₂ O
₅ Using raw materials prepared to have a composition of 5.0%,
A glass powder was prepared in the same manner as the glass powder A and subjected to a silane coupling treatment to obtain a glass powder C.

Furthermore, the weight percentage of Na ₂ O 5.0
%, K ₂ O 0.5%, MgO 3.0%, CaO 3
4.0%, SiO ₂ 46.0%, P ₂ O ₅ 11.5
Using the raw material prepared so as to have a composition of 10%, a crystallized glass powder was prepared in the same manner as the crystallized glass powder A, and a crystallized glass powder D subjected to a silane coupling treatment was obtained.

The maximum particle size of hydroxyapatite powder is 65 μm.
m or less was used.

Next, each sample was prepared using the glass powder or crystallized glass powder thus obtained. In addition, the provision form of the sample, the sample No. of the example. 2 to 10 and 13 and the sample No. which is a comparative example. Nos. 17 to 24 are powder-liquid systems, and the sample No. 1, 11-12 and 14
For ~ 16, the two-paste system was adopted.

In the case of the powder-liquid system, 0.4% by weight of benzoyl peroxide is added to 100% by weight of glass powder and crystallized glass powder, and 0% of dimethyl-p-toluidine is added to 100% by weight of monomer. .2 wt% was added.
The powder and liquid thus obtained were kneaded at the ratios shown in the table to obtain a sample.

In the case of the two-paste system, glass powder or crystallized glass powder and the monomer were kneaded at the ratio shown in the table to prepare a paste, which was then divided into two pastes in equal amounts. Next, 0.6% by weight of benzoyl peroxide was added to one paste based on 100% by weight of the paste, and the other paste was added with dimethyl-based on 100% by weight of the paste.
0.2% by weight of p-toluidine was added. Further, the obtained two pastes were kneaded to obtain a sample.

For each sample thus obtained,
The relationship between the compressive strength to obtain the fixation and the living bone was examined. The results are shown in the table.

The compressive strength is measured according to JIS-T6602 (dental zinc phosphate cement),
After thoroughly kneading each sample, the kneaded product was poured into a predetermined mold and left for 1 hour to cure, and then taken out from the mold. Further, after the cured body was immersed in the simulated body fluid for 24 hours, the wet compressive strength was measured.

The relationship with the living bone is 5 at the tibial condyle of the rabbit.
Drilled holes of × 12mm, kneaded and cured 10 × 15 × 2m
m samples were embedded. After 10 weeks, the rabbit was slaughtered, the hardened cement body and its surrounding tissue were excised, and an attempt was made to peel them off. As a result, those that cannot be peeled by hand are indicated as having a high bond strength, those that are joined but that can be peeled by hand are marked as "low", and those that were not peeled are marked as "none". Was expressed.

The curing time is measured according to JIS-T6602, and the kneaded product has a weight of 300 g and a cross-sectional area of 1
It was determined by the time when the needle of mm ² was dropped and the needle mark disappeared.

As a result, sample N which is an example of the present invention
o. Nos. 1 to 16 had high compressive strengths of 160 to 190 MPa. Moreover, it was firmly bonded to the surrounding bone so that it could not be easily peeled off by hand without causing inflammation to surrounding living tissues. In addition, self-coagulation and hardening occurred in a short time of 4 to 10 minutes.

On the other hand, sample Nos.
Although No. 24 was hardened in a short time of 6 to 10 minutes, it had a compressive strength of 115 MPa or less, and no bond was found in the bond strength with living bone, or even if the bond was found, All of them could be easily peeled off. These results will be described in further detail. Sample N using a monomer and methyl methacrylate (MMA) was used.
o. 17, 19, 22, and 24 have compressive strengths of 40 to 6
Sample N using glass powder A, which has a very low 0 MPa and has no alkaline component for binding to surrounding bone.
o. In 17 as well, it was not observed at all. On the other hand, Sample No. using Bis-GMA as the monomer. 18, 2
Regarding 0, 21 and 23, preferable results were obtained as compared with the sample using MMA, but as compared with each sample of the example using glass powder or crystallized glass powder containing no alkali component, compressive strength and It was found that the bond strength with living bone was clearly inferior.

These facts show that high strength can be obtained only by combining both alkali-free glass powder or crystallized glass powder and dimethacrylate having hydrophilicity.
In addition, it shows that a cement having high bioactivity can be obtained.

[0051]

Industrial Applicability As described above, the bioactive cement of the present invention can self-harden early and fix an implant material without inducing an inflammatory reaction to a living tissue. Moreover, since it is chemically bonded to living bone and has high mechanical strength, it is stable even when used for a long period of time.

In addition to the adhesive fixing of the implant material,
It can also be used for filling bone defects.

Further, the bioactive cement of the present invention can be used as an implant material which can be polished or cut by hardening it in advance.

Claims (14)

[Claims] 1. A surface comprising a filler composed of a non-alkali glass powder containing Ca, a monomer containing hydrophilic dimethacrylate, a polymerization initiator and a polymerization accelerator. A bioactive cement characterized in that it has a property of forming a hydroxyapatite layer in the. 2. The bioactive cement according to claim 1, wherein the alkali-free glass powder containing Ca is 20-60% by weight of CaO, 20-50% by weight of SiO ₂ , and P ₂ O ₅ 0-30 by weight percentage. A bioactive cement having a composition of wt%, MgO 0-20 wt% and CaF ₂ 0-5%. 3. The bioactive cement according to claim 1, wherein the Ca-free alkali-free glass powder is CaO 40-50% by weight, SiO ₂ 30-40% by weight, and P ₂ O ₅ 10-20 by weight percentage. Wt%, MgO 0-10
A bioactive cement having a composition of wt% and CaF ₂ 0-2%. 4. The bioactive cement according to claim 1, wherein the alkali-free glass powder containing Ca is subjected to a silane coupling treatment. 5. The bioactive cement according to claim 1, wherein the hydrophilic dimethacrylate is 2,2bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane. Bioactive cement. 6. The bioactive cement according to claim 5, wherein the monomer is triethylene glycol dimethacrylate (TEGDMA), diethylene glycol dimethacrylate (DEGDMA), or ethylene glycol diethylene in addition to the hydrophilic dimethacrylate. A bioactive cement containing at least one of methacrylate (EGDMA). 7. The bioactive cement according to claim 5, wherein the monomer is 2,2-bis (4-methacryloxyphenyl) propane (BPDMA), 2,2 in addition to the hydrophilic dimethacrylate. -Bis (4-methacryloxyethoxyphenyl) propane (Bis-ME
PP) or 2,2-bis (4-methacryloxypolyethoxyphenyl) propane (Bis-MPEPP), at least one kind of bioactive cement characterized by the above-mentioned. 8. A filler composed of alkali-free crystallized glass powder containing Ca, a monomer containing hydrophilic dimethacrylate, a polymerization initiator, and a polymerization accelerator, and when the cured product thereof contacts body fluid. , A bioactive cement having the property of forming a hydroxyapatite layer on the surface. 9. The bioactive cement according to claim 8, wherein the Ca-free alkali-crystallized glass powder is CaO 20-60 wt% and SiO ₂ 20 in weight percentage.
-50 wt%, P ₂ O ₅ 0-30 wt%, MgO 0
A bioactive cement having a composition of -20 wt% and CaF ₂ 0-5%. 10. The bioactive cement according to claim 8, wherein the alkali-free crystallized glass powder containing Ca is
Weight percentage CaO 40-50% by weight, SiO ₂ 30
-40 wt%, P ₂ O ₅ 10-20 wt%, MgO
Bioactive cement having a composition of 0-10% by weight and CaF ₂ 0-2%. 11. The bioactive cement according to claim 8, wherein the alkali-free crystallized glass powder containing Ca is
A bioactive cement characterized by being subjected to a silane coupling treatment. 12. The bioactive cement according to claim 8, wherein the hydrophilic dimethacrylate is 2,2.
A bioactive cement characterized by being bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane. 13. The bioactive cement according to claim 12, wherein the monomer is triethylene glycol dimethacrylate (TEGDMA), diethylene glycol dimethacrylate (DEGDMA), or ethylene glycol diethylene in addition to the hydrophilic dimethacrylate. A bioactive cement containing at least one of methacrylate (EGDMA). 14. The bioactive cement according to claim 12, wherein the monomer is 2,2-bis (4-methacryloxyphenyl) propane (BPDMA), 2,2 in addition to the hydrophilic dimethacrylate. -Bis (4-
Methacryloxyethoxyphenyl) propane (Bis-
MEPP) or 2,2-bis (4-methacryloxypolyethoxyphenyl) propane (Bis-MPEPP)
A bioactive cement characterized by containing at least one of the above.