JPS60142857A - Bone cement composition - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION TECHNICAL FIELD This invention relates to bone cement compositions. More specifically, the present invention relates to a cement composition for adhesion between bones and metal or ceramic materials for living bodies such as human bones and artificial joints.

Prior Art Calcium phosphate compounds, such as hydroxyagutite, and solid solutions thereof have good compatibility with living organisms and are useful as medical materials, such as alternative materials for bones or tooth roots, or prosthetic materials. be.

For example, Japanese Patent Application Laid-Open No. 56-54841 discloses a method for filling bone defects and voids using a powdered calcium phosphate compound having an apatite crystal structure.

JP-A-56-166843 discloses a filling material for bone defects and voids made of a porous body of a calcium phosphate compound. The pores contained in the porous body of this calcium phosphate compound have a maximum pore diameter of 3.0 O
m+n, the minimum pore diameter is 0.05 mm, the shape and dimensions are such that osteogenic components of the living body can easily enter, and a substantially continuous three-dimensional network structure is formed.

Conventional calcium phosphate compound ceramic materials, such as those described above, may undergo deformation over time after undergoing surgical procedures such as fillings or prostheses9, or may promote hardening of soft tissue near the filling or prosthesis. However, this poses problems such as having to remove the tissue in the area where the abnormality has occurred.

In addition, methyl methacrylate-based adhesive cement has conventionally been used as bone cement for fixing artificial bones or joints made of metal or ceramic materials in vivo, but none of these conventional Some cement! This method was not satisfactory because it contained unreacted monomers, which could be dissolved in the living body and harm the living tissue, causing fever, loosening of fixation at the surgical site, or complications from after-effects.

In general, in the treatment of defects in the hard tissues of living bodies, such as excision of bone fragments and lesions, or defects caused by external bone damage, it is most preferable to promote natural healing, and substitute artificial materials. Prosthetics are not always preferred. Even if an artificial bone cement is used to fill or prosthetize a living body, such bone cement will eventually be consumed within the living body.

The most desirable thing is for natural living tissue to regenerate in its place and complete the fixation. In this case, it is important that the rate at which the cement is replaced by living tissue (turnover rate e) is appropriate; if the turnover rate is too fast, it may cause local damage such as inflammation. This can lead to complications such as the development of cancer, etc. In addition, if the turnover rate is low and bone cement remains in the body for a long period of time, deformation of the local living tissue and hardening of nearby soft tissues may occur, requiring excision surgery. There are many things.

In order to address the above-mentioned problems, it is important that bone cement inserted into a living body can satisfy the requirements for inducing and replacing living tissue at the cellular level. In other words, it appropriately promotes the activation of anterior cells (osteoclasts) in living tissues, and promotes the invasion and development of bone-destructive cells (osteocrusts) and collagen fibers that promote the hardening of soft tissues and the hardening of bone tissues. It is important not to inhibit the infiltration of red blood cells, body fluids, etc., or the development of capillaries.

In order to meet the above requirements, the bone cement inserted into a living body must have good affinity for the living body, especially bioresponsibility, and be able to attract desired cells. It can provide a good habitat and growth space for activation, prevent the invasion of unwanted cells, and prevent the hardening of bone tissue due to abnormal development of collagen fibers.
) must be able to be prevented.

OBJECT OF THE INVENTION The object of the present invention is to provide a material that is effective for bonding biological metals or ceramic paulownia materials such as artificial bones or artificial joints, and that is effective for regenerating in-vivo bone tissue, that is, inducing new bone. It is an object of the present invention to provide an effective bone cement composition.

Structure of the Invention The bone ceramic composition of the present invention comprises (1) a sintered body of a calcium phosphate compound, and a bone ceramic composition formed in the sintered body.
A granule having one or more pores having a pore diameter of 1 to 600 microns, and a fine pore passage communicating the pores to an external space, and having a size of 0.05 to 5 microns. and,
(2) At least one selected from the group consisting of water, physiological saline, blood, and artificial plasma.

The bone cement composition of the present invention comprises sintered porous granules of a calcium phosphate compound, water, physiological saline, blood and/or artificial blood clot.

The calcium phosphate compound used in the present invention is aHPO
4 Ca5(PO4)2 Cas(POa)sOH Ca 40(PO4)2 Ca+o(PO+)6(OH)2 CaP4011 Ca(PO3)2 Ca2P207 Ca (H2PO4) 2 ・H2O etc. are the main components, and hydroxy Includes a group of compounds called apatites. Hydroxyapatite has the compositional formula Ca5(PO4)3OH or Ca+o(P
The basic component is a compound having O+)6(OH)2, and a portion of the Ca component is Sr and Ba.

Mg, Fe, At, Y, La, Na, may be substituted with one or more of H, etc., and a part of the (PO4) component is VO4, BO3, SO4, CO3.

It may be substituted with 1g1 or more such as Si04, and furthermore, a part of the (OH) component is F, C1, O, C
It may be substituted with one or more types such as O3. Hydroxyanotite may be a normal crystal, or may be any one of isomorphic solid solution, substitutional solid solution, and interstitial solid solution, and contains mild, non-stoichiometric lattice defects. Good too.

Generally, the calcium phosphate compound used in the present invention has an atomic ratio of calcium (C8) to phosphorus CP (Ca/P).
is preferably within the range of 1.30 to 1.80,
Those within the range of 1.60 to 1.67 are more preferable.

Calcium phosphate compounds used in the present invention include tricalcium phosphate (Ca3(PO4)2':l + hydroxyapatite CC[15(PO4)30H) and
Ca 1o (PO4) 6 (OH) 2 is preferred, and one synthesized by the Zorgul method and freeze-dried is particularly preferred.

Preferably, the calcium phosphate compound is preferably sintered at a temperature of 800 to 1450°C, and the sintering temperature is more preferably 850 to 1250°C.

In the granules of the present invention, the calcium phosphate compound is sintered in the form of powder, and therefore fine voids can be formed between the powder particles that are sintered in contact with each other.

The calcium phosphate porous granules of the present invention have a size of 0.05 to 5 mm, preferably 0.1 to 3 mm, and have at least one particle of 1 to 600 microns, preferably 10 microns inside. Voids with a pore diameter of ~300 microns are formed, and these pores communicate with the external space through microscopic passages. The diameter of this microgap 11j is preferably 1 to 30 microns, preferably 1 to 2 microns.
It is preferable that it be in the 0 micron range. When the granule has a plurality of pores, it is preferable that these pores communicate with each other through fine pore passages having the same diameter as above.

The sintered porous granules preferably have a porosity of 40 to 90, more preferably 60 to 70%.

It is preferable that the pores in the sintered porous granule have a shape of a straight sphere or a shape close to it, and when several pores are present, it is preferable that they are uniformly distributed within the granule.

When this pore (cjl) is implanted in a living body, it provides a living space for biologically activating canthal cells, protozoan cells, etc. 1
Li horny cells and the like prefer to stay in these pores, especially spherical pores. For this reason, the pore diameter is 1~
Must be in the range of 600 microns, 10~
Preferably it is 300 microns. Pore diameter is 1 to 6
Pores outside the 0.00 micron range cannot provide good living space for the cells.

When the shape of the hole is a true sphere or a sphere close to this,
The mechanical strength of the obtained porous material is high.

Therefore, when this porous granular paulownia material is implanted in a living body, it can maintain high mechanical strength and adhesive strength in the trench where it is returned over by new bone, and can be used as FIC.

The microporous passages in the sintered porous granules communicate at least the pores with the external space of the granules, and through these passages, the pre-mechanical cells, regenerating A+ cells, and red blood cell fluid etc. can freely enter the porous body, and the development of capillary Mn tubes is promoted. However, the diameter of the fine void passage is preferably in the range of 1 to 30 microns, more preferably in the range of 1 to 20 microns. Micro-void passages such as those shown above allow bone-destroying cells and collagen fibers to enter the capillary-like cavity passages within the porous body and prevent abnormal development of collagen fibers and hardening of bone tissue. That is, in the porous granule of the present invention, the fine void passages also function as a biofilter.

If the diameter of the microporous passageway becomes smaller than 1 micron, it may be difficult for bone aI cysts, progenitor Ml+ cysts, and broad blood cells to enter into the porous chambers, and if the diameter of the microporous passage becomes larger than 30 microns, it may be destroyed. It inhibits the invasion and development of cells and collagen fibers, thereby inhibiting bone regeneration, and may also lead to hardening of the regenerated bone tissue and surrounding tissues.

In the porous granule of the present invention, when the granule includes several pores, these pores may be connected to each other by the above-mentioned fine pore passages, and thereby, Porous・'i! It can promote the exhaustion of one body and the growth (returnover) of living tissues.

It is preferable that the porous granules of the present invention have no acute angles.

An example of the porous granules used in the present invention is shown in FIG.

In the composition of the invention, water, saline, blood and/or artificial plasma, such as polyvinylpyrrolidone,
By using preferably an amount of 10 to 200 times the weight of the granules, it is possible to promote the development of living tissue on the surface and within the pores of the porous granules used as bone cement.

If the amount of the liquid component such as water, physiological saline, blood or artificial plasma is less than 10 parts, the granules tend to scatter when the composition is used, and therefore may spread to areas other than the affected area. However, if the number exceeds 200, the granules and the liquid component may become thick.
f:! v. It may become difficult to fill the affected area with the required amount of granules.

The calcium phosphate compound sintered porous granules used in the present invention can be produced by various methods.

For example, the granules of the present invention may be prepared by mixing 30-90% by volume, preferably 30-60%, of a sublimable solid material powder with a particle size of 1-600 microns with the remaining amount of calcium phosphate compound powder. Then, this mixture is heated and stirred repeatedly with a high-speed stirrer together with an alcohol medium to form granules of 0.05 to 5 mm size containing a sublimable solid substance, and then, depending on the case, a granulator or the like is used. Use 7'lT
It is granulated into granules of fixed size, dried, heated at 300 to 50°C to remove the sublimable solid substance, and then 800°C.
It is manufactured by heating and sintering at a temperature of 9 to 1450°C, preferably 850 to 1250°C.

The calcium phosphate compound powder used for producing the above granules preferably has a particle size of 0.05 to 10 microns. Particularly preferred calcium phosphate compound powders are:
It is preferable to include a plate-shaped crystal part, and SEM
According to observation results based on scanning electron microscopy (scanning electron microscope), powder particles below 30 have a particle size of 1μ or more, and those above 70 have a particle size of 1μ.
Those having a particle size distribution having the following particle sizes are preferred.

In addition, the sublimable solid material powder is used to form pores with a desired size of 1 to 600 microns in the granules, and is easily sublimed at a temperature of 200 to 800°C, resulting in substantially no residual liquid. As long as it does not leave any residue, there are no particular restrictions on its type. Generally, the sublimable substance is selected from camphor, camphor, naphthalene, and mixtures of two or more thereof.

When the granulated mixture granules are heated to a temperature of 200 to 800°C, preferably for 120 to 180 minutes, the sublimable substance sublimates and escapes, forming pores. At this time, fine particles of the sublimable substance are removed from the pores. Sublimation and escape of the powder forms microvoid passages communicating with the outside of the porous body. Further, microscopic void spaces are also formed that communicate between the holes.

Next, the molded product is heated again at 800 to 1450°C, preferably at 85°C.
The calcium phosphate compound powder is sintered by heating to 0 to 1200°C, preferably for 1 to 3 hours.

In the method using the above-mentioned sublimable substance powder, 1 to 5
Parts by weight of organic fibers having a length of 1 to 5 barrels and a diameter of 1 to 30 microns may be added. Such a mixture is heated to a temperature of 200-800°C, preferably 120-18°C.
When heated for 0 minutes, the sublimable substance sublimates and escapes, and the organic fibers are carbonized. Next, at a temperature of 800 to 1450 °C,
Preferably, by heating for 1 to 3 hours, the carbide is burned out and the calcium phosphate compound powder is sintered.

In this method, the incorporation of organic fibers is effective in ensuring the formation of capillary-like void passages having a diameter of 1 to 30 microns. This organic fiber is similar to that described above.

When mixing organic fibers or sublimable material powder with phosphoric calcium compound powder, adding a volatile lower alcohol such as methanol or ethanol not only makes it easier to obtain a homogeneous mixture, but also reduces the particle size of the sublimable material particles. control,
In addition, it is possible to improve the adhesion between the sublimable material particles and the organic fibers, thereby promoting the formation of fine void passages communicating with the pores.

Another method for producing the porous granules of the present invention is as follows:
~90 volume units, preferably 30 to 60 volume units, 1 to 6
1 organic synthetic resin particle having a particle size of 0.00 microns.
00 parts by weight of calcium phosphate compound powder, this mixture is molded into a desired shape and size by a method similar to the method described above, and the obtained molded product is heated to a temperature of 200 to 800°C to perform the organic synthesis. The resin particles are removed by thermal decomposition, and then the calcium phosphate compound powder is sintered by heating to a temperature of 800 to 1450° C. in an oxygen-containing atmosphere.

The organic synthetic resin particles having a particle size of 1 to 600 microns used in the above method are effective for forming pores of 1 to 600 microns in a porous body. There are no particular limitations on the synthetic organic resin as long as it thermally decomposes at a temperature of 200 to 400°C and escapes from the porous body, but in general, methyl methacrylate, borine 00 pyrene, It is selected from highly desirable plastic synthetic resins such as polystyrene, and methyl methacrylate is particularly preferred. Since the organic synthetic resin described above has a certain hardness, the spherical particles will not be deformed or crushed when the particles are mixed with calcium phosphate compound powder or when this mixture is press-molded. It is possible to form pores with a size and shape that precisely correspond to the size and shape of the particles used.

A mixture of organic synthetic resin spherical particles and calcium phosphate compound powder is formed into granules having desired dimensions and shape. The obtained granules are first heated at a diopter of 200 to 500°C, preferably 300 to 350°C, for 120 to 180 minutes to remove the organic synthetic resin particles by thermal decomposition and form corresponding pores. At the same time, micro-void passages extending from the pores are formed.

Next, this molded product was heated to a temperature of 800 to 145% in an oxygen-containing atmosphere.
0°C, preferably 850-1250°C, preferably 1
Heat for ~3 hours to sinter the calcium phosphate compound powder. At this time, even if there is a thermal decomposition residue of the organic synthetic resin particles, this is burned off during sintering and heating.

In the method using the organic synthetic resin particles, 100
For every part by weight of calcium phosphate powder, 1 to 5 parts by weight of organic fibers having a length of 1 to 5 microns and a diameter of 1 to 30 microns can be added. The types and effects of this organic fiber are the same as described above.

Furthermore, in the method using the organic synthetic resin particles,
100'i [for i part of calcium phosphate compound powder,
2 to 5 weight stones: Sublimable solid material particles having a particle size of 1 to 600 microns can be additionally added. The dimensions of this sublimable material are the same as above. In this method The sublimable material particles have a particle size of 1 to 600 microns and are effective in forming capillary layer-like void passages.

Historically, in the method using the organic synthetic resin particles, 2 to 5 parts by weight of particles having a length of 1 to 5 ends and a diameter of 1 to 30 microns per 1 part of 100 parts by weight of calcium phosphate compound powder. Organic fibers and 2 to 5 parts, 1 to 6
Sublimable solid particles having a particle size of 0.00 microns may be additionally mixed. The types and effects of these organic fibers and sublimable solid particles are the same as described above.

The granules obtained by the above manufacturing method have pores of 1 to 600 μm that can be penetrated by bone cells, and are sharp.

It shows an external shape without corners, and the particle size of the granules is 0.05~
Can be adjusted to any size in 5 sizes, and the firing temperature can be adjusted from 800 to 1
Any temperature of 450℃? ! li! Since the degree can be selected, it is possible to adjust the turnover rate. When using the above granules as bone cement, water,
Chemical 111 saline, patient's blood and/or artificial blood samples, including vinylpyrrolidone, are used.

Bone cement composition Phantom 1 of the present invention can be used, for example, as follows.

In Fig. 2, the artificial bone cement plug 5 is inserted into the bottom of the femoral hip joint head which has been cut to form the medullary cavity, and then the stem of the alumina artificial hip joint 1 is inserted. Bone cement composition 4 between the stem and the bone marrow
,3. and fill 2. At this time, bone cement compositions 4, 3. The sizes of the granules and 2 may be made smaller sequentially. The plug 5 has a diameter of 1 to 600 microns, preferably 300 to 60 microns, similar to the granules of the present invention.
A sintered porous body of a phosphorus dicalcium compound having a large number of pores having a pore diameter of 0.0 microns and a microscopic pore passage communicating the pores with the outside space is used.

The size and shape of the stopper may be of any size and shape as desired.

Further, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to the examples.

Example: By a known wet method, calcium phosphate with Ca/p = 1.65 was synthesized by dropping a phosphoric acid solution into calcium hydroxide slurry, and after drying, a To 100 g of this calcium phosphate, 37 g of polymethyl ivy acrylate resin with a slip diameter of 5 to 300 μm was mixed, and this mixture was heated at high speed 1.
'I. Using a beating machine, heat and stir repeatedly using methanol as a medium, and then use a transfer granulator to form unfired granules with no sharp edges of 0.1 to 3. Granulated. The granules were heated at 300°C for 24 hours to remove heat from the organic synthetic resin particles to obtain a porous body with pores of 5 to 300μ, and then sintered at 1000°C for 1 hour to remove heat from the organic synthetic resin particles. 300
Porous granules of 01 to 3++Im having pores of μ were obtained.

This is divided into grain sizes of 0.1 to 0.15 mm and 0.3 to 0.
．． 5 mm.

It was divided into 31 pieces of 0.8 to 1.2 mm. A microscopic photograph of the crushed granules is shown in FIG.

Separately, add 100g of calcium phosphate powder to 300~6
Polymethyl methacrylate-1-resin 40& having a particle size of 00 μm was added, mixed and dried using methanol as a medium, and the mixture was packed in a rubber balloon and subjected to hydrostatic pressure pressing at 300 kV/crn2 to give a molded product a dark blue color. This molded body was gradually heated to 300°C from room temperature to remove the organic synthetic resin particles by thermal decomposition to obtain a porous body having pores of 300 to 600 μm in continuous A/ζ. Sinter for 1 hour at ℃, then cool down to a diameter of 5 mm.

A cylindrical bone cement plug with five continuous holes in length was obtained. The plug thus obtained had a porosity of 55 cm.

Figure 2 shows an example in which these granules and plugs were actually removed from a dog's hip joint, the femoral head was cut off, an alumina artificial hip joint was used in its place, and the bone cement of the present invention was used at the same time. Shown below.

In FIG. 2, the alumina artificial hip joint 1 is placed over the cut bone head, the bone head is inserted into the bone marrow cavity, and the stem is inserted into the medullary cavity.
The bone cement of the present invention was used between bones and the induction of new bone and fixation of the artificial hip joint were observed. A plug 5 of the bone cement of the present invention is fixed under the stem, and the granules 058 of the present invention are fixed.
~1.2 mm, 4, then 0.3~05 mm of granule 3, and finally 01~0.15 mm of granule 2 are injected together with physiological saline, and immediately insert the artificial femoral head stem. was pushed into the diaphysis, the stem was fixed, and the stem was reduced. In addition, 6 is the dog's thigh 11. Two weeks later, the dog's large 11i1 bone was removed and its progress was observed after surgery.
As a result, a large amount of new bone formation was observed in areas 7 and 8 where loads were particularly applied, and a slight induction of new bone 11 was observed in other areas as well. From the guanku after 13 weeks, there is no human.
The hip joint is fixed to the dog's femur without evacuation, and after the surgery, in areas 7 and 8 where the load is applied, the granules are mostly replaced with fresh bone Ii, and other The granules at the site were also covered with IA neophyte, but there was also some neoplasia of the medullary cavity. The granules used are water,
Physiological saline, patient's blood, or artificial plasma (1)
Since seeds are added and used, the granule surface and pores are covered with living tissue in vivo.

Furthermore, the granules of the present invention have pores and therefore have a large surface area. Therefore, in a short period of time, young granulation tissue covers the surface and the formation of larval eyes begins rapidly, and then new bone is formed between the granules and begins to bridge, and as the granulation tissue develops, new bone including cancellous bone begins to form. It is formed. In particular, in the case of artificial hip joints, this phenomenon appears prominently in the areas where the load is applied.

Fc) New bone formation occurs even in areas that are not affected. Furthermore, in the area where the load is applied, all of the granules are connected to new bone and dense cancellous bone is formed in a short period of time, and the new bone continues to become denser, causing the artificial joint and surrounding The artificial joint can be completely fixed by transitioning to compact bone with the same tissue.

Thereafter, new bone is gradually formed even in areas where no load is applied, and eventually all of the granules are replaced by new bone. Furthermore, in order to increase the bone formation rate, it is preferable to increase the specific surface area of the granules and increase the number of granules, but for new bone formation, it is necessary to supply osteogenic substances from within the body. Since it is essential, it naturally has its limits. Therefore, in the bone cement composition of the present invention, the bone formation rate can be adjusted by selecting the sintering temperature, pore size, and granule diameter during granule production. That is, the sintering temperature of the granules used in the bone cement composition of the present invention is 800-1350.
℃, preferably 850 to 1250℃, the pore size is 1
-600μ, preferably 5-300μ, and the size of the granules is 0.05-5, preferably 0.1-3.

More preferably, by using a cement plug, the length of the granules can be adjusted to 01~015, 0, β~
By using three types of granules, 0.5 (transfer) and 0.8 to 1.2, and using the largest granule from the bottom, it is possible to adjust the bone formation rate. In addition, since the bone cement plug has a continuous winter hole, bone marrow flows through the bone cement plug filled in the bone marrow cavity, and the bone cement of the present invention comes into contact with the bone jν1 and further stimulates new growth. Can promote bone formation. In the bone cement composition of the present invention, new bone is formed within the marrow cavity, but unnecessary new bone within the marrow cavity is formed by osteoclasts. It is absorbed by the body, leaving new bone only in the necessary areas. For the reasons mentioned above, the bone cement composition of the present invention replaces conventional bone cements and makes it possible to strengthen the surrounding tissue and completely fix the artificial joint.

[Brief explanation of drawings]

Fig. 1 is a microscopic photograph (500x magnification) of granule particles used in the bone cement composition of the present invention, and Fig. 2 shows an example of the usage situation of the bone cement composition of the present invention. It is an explanatory diagram. 1... Artificial hip joint, 2... Granule layer with particle size of 0.1-015mm, 3... Granule layer with particle size of 0.3-0.5++on, 4... Particle size of 08-08mm 12 granular body layer, 5...
Bone cement plug, 6...femur, 7.8...load concentration area. Patent Applicant Sumitomo Cement Co., Ltd. Patent Application Agent Patent Attorney '11 Hon Ro Patent Attorney Kazuyuki Nishidate Patent Attorney Akira Yamaguchi Patent Attorney Masaya Nishiyama

Claims (1)

[Scope of Claims] 1. A sintered body of a calcium phosphate compound; one or more pores having a pore diameter of 1 to 600 microns formed in the sintered body; A granule having a microvoid passage communicating the pores with the external space and having a size of 0.05 to 5 mm, and selected from the group consisting of water, physiological saline, blood, and artificial plasma. A bone cement composition comprising at least one. 2. A bond in which the atomic ratio of calcium to phosphorus in the calcium phosphate compound is within the range of 1.30 to 1.80.
IU composition according to claim 1. 3. The composition of claim 1, wherein the calcium phosphate compound is hydroxyapatite. 4. The composition according to claim 1, wherein the pore diameter is within the range of 3 to 3 oo microns. 5. The composition according to claim 1, wherein the diameter of the microvoid passage is within the range of 1-ao micron. 6. The composition according to claim 1, wherein the granules have a porosity of 40 to 90. 7. The composition according to claim 1, wherein the granules have a plurality of pores, and these pores communicate with each other through fine pore passages. 8. The calcium phosphate compound sintered body is 800 to 145
A composition according to claim 1, which is sintered at a temperature of 0°C. 9. The composition according to claim 1, wherein the addition tt of at least one of water, physiological saline, blood, and artificial plasma is 10 to 200φ with respect to the granule weight penalty.