JPH08280789A - Bioactive cement composition and two paste bioactive cement - Google Patents

Abstract

PURPOSE: To retain mechanical characteristics without deterioration in spite of implantation in the loving body over a long period of time and to improve shape maintaining property by composing the above compsn Ca-contg. non- alkaline glass powder, fused silica powder, dimethyl acrylate monomer, polymn. initiator and polymn. accelerator. CONSTITUTION: This two paste bioactive cement consists of the first paste prepd. by mixing the polymn. initiator with the Ca-contg. non-alkaline glass powder, the fused silica powder and the dimethyl acrylate monomer and the second paste mixed with the polymn. accelerator. The Ca-contg. non-alkaline glass powder elutes Ca ions in the living body and exhibits bioactivity. Glass or crystallized glass having a compsn. consisting, by weight per cent, of 30 to 70% CaO, 30 to 70% SiO2 , 0 to 40% P2 O5 , 0 to 20% MgO and 0 to 5% CaF2 and more particularly a compsn. consisting of 40 to 50% Cab, 30 to 40% SiO2 , 10 to 20% P2 O5 , 0 to 10% MgO and 0 to 2% CaF2 is preferably used for the glass powder described above.

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 artificial biomaterials and filling bone defects in the fields of orthopedics, neurosurgery and oral surgery.

[0002]

2. Description of the Related Art In the field of orthopedics, when bone is partially lost due to a fracture or bone tumor, or when part of the bone is excised by surgery, or in the field of oral surgery due to tooth extraction or alveolar pyorrhea. When a defect occurs in the jawbone, an artificial biomaterial made of metal, ceramics, crystallized glass or the like is used to repair such a part.

[0003] It is desirable that such an artificial biomaterial be embedded and fixed in the repaired portion at an early stage with good compatibility. For that purpose, it is necessary to process it according to the shape of the repaired portion. It is very difficult to perform the processing accurately.

Therefore, when an artificial biomaterial is used, a biomedical bone cement is generally used for the purpose of adhering and fixing the artificial biomaterial. For example, polymethylmethacrylate (PMMA) cement is widely used in the orthopedic field, and zinc phosphate cement and carboxylate cement are used in the oral surgery field.

However, the above-mentioned various types of biomedical bone cements firmly adhere to the artificial biomaterials but do not chemically bond to the biomedical bones. , May cause inflammatory reaction in surrounding tissues.

Under these circumstances, various bone cements for living body which are chemically bonded to living bone have been developed in recent years. For example, a bioactive cement composed of a glass powder containing Ca, a dimethacrylate monomer, a polymerization initiator and a polymerization accelerator has been proposed.

[0007]

The above-mentioned bioactive cement, which hardens in the living body and then elutes Ca ions, reacts with PO ^4- ions in the body fluid to precipitate hydroxyapatite. Therefore, it is easily combined with natural bone.

However, as a result of this cement releasing ions continuously in the living body over a long period of time, the mechanical properties of the hardened cement material deteriorate significantly. Further, it has a drawback that the shape retention property is poor, and when it is used for a curved surface portion such as a skull in neurosurgery, dripping is likely to occur.

An object of the present invention is to provide a bioactive cement which does not deteriorate in mechanical properties even when it is embedded in a living body for a long period of time and is excellent in shape retention.

[0010]

As a result of various experiments, the inventors of the present invention have found that the above object can be achieved by substituting a part of bioactive glass powder with a fused silica powder which is not harmful to human body. I found it.

That is, the bioactive cement composition of the present invention is characterized by comprising a Ca-containing alkali-free glass powder, a fused silica powder, a dimethacrylate monomer, a polymerization initiator, and a polymerization accelerator. .

The two-paste bioactive cement of the present invention comprises a Ca-containing alkali-free glass powder, a fused silica powder, a first paste prepared by mixing a dimethacrylate monomer and a polymerization initiator, and a Ca-containing alkali-free glass. It is characterized by comprising a second paste formed by mixing powder, fused silica powder, dimethacrylate monomer and polymerization accelerator.

Alkali-free glass powder containing Ca is one which elutes Ca ions in the living body and exhibits bioactivity. As such glass powder, CaO in weight percentage
_{30~70%, SiO 2 30~70%,} P 2 O 5 0~
40%, MgO 0-20%, CaF ₂ 0-5%, especially CaO 40-50%, SiO ₂ 30-40%, P ₂ O
₅ 10-20%, MgO 0-10%, CaF ₂ 0-2
It is desirable to use glass or crystallized glass with a% composition. In the crystallized glass powder having the above composition, apatite crystals and wollastonite crystals are deposited inside.

The reason for limiting the glass composition in this way is as follows. When CaO is less than 30%, Ca ²⁺ ions are difficult to elute, bioactivity is reduced, and the binding force with bone is reduced. If it is more than 70%, the devitrification becomes too strong and it becomes difficult to vitrify. If the SiO ₂ content is less than 30% or more than 70%, the devitrification becomes too strong and vitrification becomes difficult. P ₂ O ₅ is a component that improves the meltability of the glass, but if it is more than 40%, the chemical durability becomes poor and it tends to be eroded in the living body. MgO is also a component that improves the meltability of glass, but if it exceeds 20%, the strength of the glass decreases and the chemical bond strength with bone also decreases. When CaF ₂ is more than 5%, devitrification becomes remarkable, and it becomes difficult to obtain a homogeneous glass. The reason for limiting the use to non-alkali glass is as follows. That is, when the glass powder or the crystallized glass powder contains an alkaline component, the chemical durability of the glass is significantly lowered, and the powder collapses during long-term implantation in the living body. 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, when an alkaline component is contained, this elutes to form a thick and brittle silica gel layer on the surface of the glass powder, resulting in the inconvenience that it cannot be firmly bonded to the living bone.

The Ca-containing alkali-free glass powder preferably has a smaller particle size because a higher strength cement can be obtained. Specifically, it is preferably 44 μm or less. In addition, if the surface is subjected to silane coupling treatment, the compatibility with the dimethacrylate-based monomer will be improved and the strength of the cement hardened product will be increased, and since the powder surface has a hydrophobic group, there will be no inhibitory effect on blood, The cement will harden easily.

The fused silica powder is not harmful to the living body and is excellent in mechanical strength and chemical durability. The fused silica powder can be used in any shape such as a crushed shape or a bead shape, but it is preferable to use a bead shape in order to increase the filling rate and improve the mechanical strength and shape retention. desirable. Moreover, the size is 1 to 10 μm in order to improve the mechanical strength and to obtain a good feeling during work.
It is preferably m.

In the present invention, the content ratio of Ca-containing alkali-free glass powder and fused silica powder is 25:
It is preferably from 75 to 95: 5. This is because if the proportion of fused silica powder exceeds this range, the ability to bind to bone in vivo will be extremely reduced. On the other hand, if the amount of the fused silica powder is too small, it becomes difficult to prevent the mechanical strength of the hardened cement product from being deteriorated, and the shape maintainability is deteriorated.

The dimethacrylate-based monomer used in the present invention is a polyfunctional monomer and, when polymerized, becomes a polymer having a very high mechanical strength. As a dimethacrylate-based monomer, 2,2 bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane (Bis- is easily available and is not harmful to the body.
GMA) is particularly preferable, but other than this, 2,2-bis (4-methacryloxyphenyl) propane (BPDM
A), 2,2-bis (4-methacryloxyethoxyphenyl) propane (Bis-MEPP), 2,2-bis (4-methacryloxypolyethoxyphenyl) propane (BiS-MPEPP) and the like can be used. . If the monomer has a too high viscosity and is difficult to handle, it may be used together with a monomer having a low viscosity. As such a monomer, triethylene glycol dimethacrylate (TEGDMA) is preferable, but it is also possible to use a polymerizable monomer such as diethylene glycol dimethacrylate or ethylene glycol dimethacrylate.

The powder-liquid ratio of the powder to the monomer is preferably 50:50 to 90:10 by weight: powder: monomer. This is because when the proportion of the monomer is higher than this range, the viscosity becomes too low, and the dispersion state of the powder in the monomer becomes non-uniform, or the powder tends to settle by the time the curing is completed. Become. On the other hand, when the proportion of the powder is too large, the monomer is insufficient and a matrix cannot be formed at the interface of the powder, so that the cured body tends to become brittle.

As the polymerization initiator, benzoyl peroxide is most preferable, but tri-n-butylborane and the like can be used in addition. It is also possible to use a photopolymerization type by using a sensitizer such as dl-camphorquinone. The addition amount of these polymerization initiators is preferably 0.1 to 5 parts by weight with respect to 100 parts by weight of the monomer. The reason for limiting the amount added in this way is that the polymerization initiator is 0.1
If the amount is less than 5 parts by weight, there is almost no effect, and if the amount is more than 5 parts by weight, the curing time becomes too fast and the workability deteriorates even if a large amount of the polymerization inhibitor is used.

As the polymerization accelerator, a tertiary amine such as dimethyl-p-toluidine can be used, and the addition amount thereof is preferably 0.1 to 5 parts by weight with respect to 100 parts by weight of the monomer. . The reason for limiting the amount added in this way is that if the polymerization accelerator is less than 0.1 parts by weight, it will not cure unless heated to 100 ° C. or higher when the monomer is polymerized, which makes it difficult to use in an actual operating room. On the other hand, if it is more than 5 parts by weight, the curing time will be too fast and the workability will be deteriorated even if a large amount of the polymerization inhibitor is used.

Further, in the present invention, various components can be added in addition to the above components.

For example, phenothiazine or its derivative can be added as a polymerization inhibitor. Phenothiazine and its derivatives have almost no toxicity to the living body and can be adjusted to a target curing time with a comparatively small amount. Moreover, even if the curing time is lengthened, the working time only increases, from the start of gelation to the end of curing. Since it hardly affects the time, it is preferred as a polymerization inhibitor. The amount of the polymerization inhibitor added is from 10 ppm to 0.
2 parts by weight is suitable.

In addition to the polymerization inhibitor, colloidal silica, resin powder, drug, bone formation promoting substance and the like can be added to the bioactive cement of the present invention.

The bioactive cement composition of the present invention is provided in a powder-liquid system (a powder system is a glass powder and a polymerization initiator, a liquid system is a monomer and a polymerization accelerator) or a two-paste system (one of The paste has glass powder, a monomer, and a polymerization initiator, and the other paste has a glass powder, a monomer, a polymerization accelerator, etc., and the user may use the powder and the liquid in each form, or mix the pastes with each other. . It should be noted that which form should be adopted may be determined in consideration of various conditions, but the two-paste system is preferable in consideration of the mixing property of the powder and the resin in the operating room.

[0026]

When the bioactive cement composition of the present invention is cured, Ca ²⁺ is produced from the glass powder exposed on the surface of the cured product.
Ions are eluted and react with PO ^4- ions in the body fluid to precipitate hydroxyapatite. Therefore, the hardened body and natural bone are easily bonded. On the other hand, the fused silica powder does not release ions in the living body, so that it does not deteriorate and remains as a skeleton of the cured product, which prevents the strength of the cured product from decreasing.

[0027]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail based on embodiments.

Table 1 shows examples of the present invention (Sample Nos. 1 to 1).
5) and Table 2 show comparative examples (Sample Nos. 6 and 7).

[0029]

[Table 1]

[0030]

[Table 2]

Each sample of the examples was prepared as follows.

First, in terms of weight percentage, CaO 44.7%,
SiO ₂ 34.0%, P ₂ O ₅ 16.2%, MgO
The raw material prepared so as to be a glass having a composition of 4.6% and CaF ₂ 0.5% was melted at 1500 ° C. for 2 hours, vitrified, and then roll-formed. Next, this glass molded body was crushed with a ball mill and then classified to obtain a maximum particle size of 44.
A glass powder having a size of μm or less was obtained. Further, the same glass molded body as above was fired at 1050 ° C. for 4 hours to be crystallized, then crushed using a ball mill and classified to obtain crystallized glass powder having a maximum particle size of 44 μm or less. Then, 1% by weight of γ-methacryloxypropyltrimethoxysilane was added to the glass powder or the crystallized glass powder, mixed in a ball mill, and dried at 120 ° C. for 2 hours to subject the powder surface to silane treatment.

Further, a bead-like fused silica powder having an average particle diameter of 3 μm was prepared. The surface of the fused silica powder was treated with silane in the same manner as the glass powder.

Next, Bis-GMA and TE are used as monomers.
G-DMA was mixed at a weight ratio of 1: 1 and mixed with 2: 1.
Divided into two equal parts. Similarly, each of the glass powder and the fused silica powder was equally divided into two.

Subsequently, one monomer, half of the glass powder, half of the molten glass powder and benzoyl peroxide were added and kneaded to obtain a first paste. Further, the other monomer, the remaining powder, dimethyl-p-toluidine and phenothiazine were added and kneaded to obtain a second paste, and a sample was obtained.

The composition ratios of the powders in the table are the composition ratios of the glass powder and the fused silica powder in% by weight.
Further, in order to cure in about 7 minutes, benzoyl peroxide, dimethyl-p-toluidine, and phenothiazine were added in an amount of 2 parts by weight per 100 parts by weight of the total amount of the monomers, respectively.
It was 1.4 parts by weight and 300 ppm.

Sample No. which is a comparative example. No. 6 uses only glass powder as a powder component, and the others use No. 6 of the example. It was prepared in the same manner as the sample of No. 5. In addition, sample No. No. 7 used commercially available PMMA cement.

For each of the samples thus produced,
The flexural strength, the presence or absence of an inflammatory reaction, and the bioactivity at 3 and 6 months after the in vivo implantation were evaluated.

The bending strength was evaluated by a three-point bending test, and each sample was kneaded and cured to obtain 3 × 4 × 20.
mm specimens were prepared to measure the initial strength, and after being implanted subcutaneously in the rat, the specimens were taken out after 3 months and 6 months, and then measured. The presence or absence of an inflammatory reaction was evaluated by observing a soft tissue around a sample piece implanted subcutaneously in a rat with a microscope and evaluating the appearance of tumor and the presence of necrosis. The bioactivity was judged by whether a Ca-P rich layer was formed. The Ca-P rich layer was confirmed by observing the surface of the embedded sample piece with an electron microscope and performing an EPMA line analysis.

As a result, as is apparent from Table 2, Sample No. containing no fused silica powder. It was found that Comparative Example 6 did not cause an inflammatory reaction in the surrounding tissues and exhibited bioactivity. However, the initial strength is 107 MPa,
85 MPa 3 months after implantation in the body, 3 after 6 months
The strength was remarkably deteriorated to 6 MPa. Sample No. made of PMMA cement. No. 7 did not cause an inflammatory reaction of surrounding tissues, and had an initial bending strength of 92 MPa,
88 MPa 3 months after implantation in the living body, 87 MPa 6 months after implantation
And there was almost no deterioration in strength. However, this cement does not show any formation of a Ca-P rich layer on the surface of the hardened body, and it is clear that it has no bioactivity.

On the other hand, sample No. which is an example of the present invention. 1
It was found that -5 showed bioactivity without causing an inflammatory reaction of surrounding tissues. Regarding bending strength, the initial strength is 12
0 to 142 MPa, 110 to 13 within 3 months after implantation in vivo
1 MPa, 104 to 120 MPa after 6 months, and sample No. It can be seen that the strength deterioration is considerably less than that of No. 6. In addition, the sample No. that had the lowest strength after 6 months had elapsed. Sample 2 made of PMMA cement
o. The value was higher than 7.

[0042]

Industrial Applicability As described above, the bioactive cement composition of the present invention does not induce an inflammatory reaction to living tissues because it has no biotoxicity, and exhibits high bioactivity. Can chemically bond with bone. Further, it has high mechanical strength, and its mechanical characteristics are hardly deteriorated even when it is implanted in a living body for a long period of time. Furthermore, the shape retention property is excellent, and even if the affected area is filled, dripping is unlikely to occur.

Therefore, the fields of orthopedics, neurosurgery,
It is suitable as an adhesive when applying artificial bones, artificial joints, artificial tooth roots, etc. in the field of the field of oral surgery, etc., or as a filler for filling defect parts of bones and teeth.

By providing in the form of 2 pastes, the mixing work is easy and the work can be performed efficiently in the operating room.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location C08F 4/34 C08F 4/34 20/26 MMV 20/26 MMV (72) Inventor Takehiro Shibuya Shiga Prefecture 2-7-1, Harashira, Otsu-shi NIPPON Glass Glass Co., Ltd.

Claims (14)

[Claims] 1. A bioactive cement composition comprising a Ca-free alkali-free glass powder, a fused silica powder, a dimethacrylate monomer, a polymerization initiator, and a polymerization accelerator. 2. A Ca-containing alkali-free glass powder comprising CaO 30 to 70% and SiO ₂ 30 to 70% by weight.
_{%, P 2 O 5 0~40%} , 0~20% MgO, CaF
_The bioactive cement composition according to claim 1, having a composition of _{20 to} 5%. 3. The fused silica powder has an average particle size of 1 to 10 μm.
2. The bioactive cement composition according to claim 1, which is in the form of beads of m. 4. The bioactive cement composition according to claim 1, wherein the weight ratio of the Ca-containing alkali-free glass powder to the fused silica powder is 25:75 to 95: 5. 5. The dimethacrylate-based monomer is 2,2
The bioactive cement composition according to claim 1, comprising bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane and triethylene glycol dimethacrylate. 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. A first paste obtained by mixing Ca-containing alkali-free glass powder, fused silica powder, dimethacrylate-based monomer and a polymerization initiator, Ca-containing alkali-free glass powder, fused silica powder and dimethacrylate-based monomer. A two-paste bioactive cement, characterized in that it comprises a second paste obtained by mixing the above with a polymerization accelerator. 9. A Ca-containing alkali-free glass powder comprising CaO 30-70% and SiO ₂ 30-70 in weight percentage.
_{%, P 2 O 5 0~40%} , 0~20% MgO, CaF
The two-paste bioactive cement according to claim 8, which has a composition of _{20 to} 5%. 10. The fused silica powder has an average particle size of 1-10.
9. The two-paste bioactive cement according to claim 8, which is in the form of beads having a diameter of μm. 11. The two-paste bioactive cement according to claim 8, wherein the weight ratio of the Ca-containing alkali-free glass powder and the fused silica powder is 25:75 to 95: 5. 12. The dimethacrylate-based monomer is 2,
9. Bis [4- (3methacryloxy-2-hydroxypropoxy) phenyl] propane and triethylene glycol dimethacrylate.
No. 2 paste bioactive cement. 13. The two-paste bioactive cement according to claim 8, wherein the polymerization initiator is benzoyl peroxide. 14. The two-paste bioactive cement according to claim 8, wherein the polymerization accelerator is dimethyl-p-toluidine.