JPH0416539A - Hydraulic calcium phosphate 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 <Industrial Application Field> The present invention provides a hydraulic calcium phosphate cement that can be used as a medical cement capable of filling bone defects and bone voids, a tooth root canal filling material, etc. Regarding the composition.

<Prior Art> Calcium phosphate hydraulic cement compositions are useful as tooth and bone repair materials because they are converted into compounds similar to the main components of teeth and bones in living organisms through setting and hardening, and are also useful as biopolymer materials. It is known to be useful as an adsorbent for harmful organic substances or inorganic ions in living organisms.

Conventionally, such calcium phosphate hydraulic cement compositions have used a combination of salts and diluted salts as a hardening liquid (for example, Japanese Patent Application Laid-Open No. 59-88351) or contained unsaturated carboxylic polymers. An acidic solution was used (for example, JP-A No. 60-253454)
. However, in such conventional calcium phosphate hydraulic cement compositions, the hardening liquid is highly acidic and causes considerable irritation to living organisms until the hardening of the cement is completed. Furthermore, even after the cement has finished hardening, the pH decreases due to the elution of unreacted acids, resulting in the problem of irritation to living organisms.

To solve this problem, calcium phosphate hydraulic cement compositions that harden with water have been developed (for example, FCREPORT, vol.

6 (1988), P, 475-480 "Hydraulic apatite as bioceramics"). Several types of calcium phosphate hydraulic cement compositions that harden with water have been developed to date.1 For example, a calcium phosphate hydraulic cement composition that hardens in about 10 minutes at 37°C by simply kneading with water (Japanese Patent Application Laid-open No. Showa 64-374
No. 45) is known. This calcium phosphate hydraulic cement composition has an approximately neutral pH and is less irritating to living organisms, thus solving the problems of conventionally known calcium phosphate hydraulic cement compositions.

However, the calcium phosphate hydraulic cement composition contains α-type tertiary calcium phosphate.

It is characterized by being mixed with dibasic calcium phosphate dihydrate at a Ca/P molar ratio of 1.20 to 1.47, and has a problem of relatively low strength. Although the strength can be increased by bringing the Ca/P molar ratio closer to 1.50, it has the disadvantage that the curing time is significantly delayed. In addition, it is desirable for such a hydraulic calcium phosphate cement composition to gradually convert into an apatite structure in vivo after hardening, from the viewpoint of biocompatibility.
This occurs more easily as the P molar ratio approaches 1.50.

It is desired to develop a hydraulic calcium phosphate composition with a Ca/P molar ratio closer to 1.50.

<Problems to be Solved by the Invention> Therefore, an object of the present invention is to provide a hydraulic calcium phosphate composition that can be cured quickly at a pH around neutrality, and that can provide a cured product with high strength and excellent biocompatibility. It's about providing things.

<Means for Solving the Problems> According to the present invention, the Ca/P molar ratio of α-type tertiary calcium phosphate and dibasic calcium phosphate is as follows.

1.400 to 1.498, and a hardening liquid, and the mixed powder and/or the hardening liquid contain monocalcium phosphate. A hydraulic calcium phosphate cement composition is provided.

The present invention will be explained in more detail below.

The hydraulic calcium phosphate cement composition of the present invention has a cement composition containing a specific mixed powder material and a hardening liquid,
By simply mixing with the hardening liquid, the α contained in the cement composition can be
The type tertiary calcium phosphate and the second calcium phosphate react to produce octacalcium phosphate, and the crystals become entangled and harden. At this time, the monocalcium phosphate contained in the mixed powder material and/or the hardening liquid acts as a hardening accelerator.

In the present invention, the mixed powder material contained as an essential component in the cement composition includes α-type tertiary calcium phosphate and tertiary calcium phosphate.
As the calcium phosphate, a' secondary calcium phosphate may preferably include commercially available secondary calcium phosphate dihydrate. The mixing ratio of the α-type tertiary calcium phosphate and the dibasic calcium phosphate is Ca
/P molar ratio is in the range of 1.400-1.498.

When the Ca/2 molar ratio is less than 1.400, the strength of the cured product decreases, and furthermore, the acidity increases, making it difficult to convert into apatite, for example, in a living body.

Moreover, if it exceeds 1,498, the curing time will be delayed, so it is necessary to keep it within the above range.

Further, the hardening liquid used in the hydraulic calcium phosphate cement composition of the present invention is not particularly limited, but examples include water.

In the present invention, monobasic calcium phosphate is contained as an essential component in the mixed powder material and/or the curing liquid.

Preferable examples of the monobasic calcium phosphate include monobasic calcium phosphate monohydrate. The amount of the monobasic calcium phosphate added is preferably 0.01 to 5.0% by weight, particularly preferably 0.2 to 1.0% by weight, based on the entire hydraulic calcium phosphate cement composition. If it is less than 0.01% by weight, no promoting effect will appear;
If it exceeds 5.0% by weight, it is not preferable because it causes irritation to living organisms due to a decrease in pH and deteriorates operability due to a shortening of curing time.

Furthermore, in the present invention, water-soluble sodium salts can be further included in the mixed powder material and/or the curing liquid in addition to the primary calcium phosphate. Examples of the water-soluble sodium salts include sodium succinate, sodium lactate, sodium acetate, and sodium chloride, which can be used alone or as a mixture. In this case, sodium succinate and sodium lactate are particularly preferred because they have a particularly remarkable effect of accelerating hardening and promote the reaction of converting the hardened product into apatite in the living body. Further, succinic sodium is most preferable because it can increase the strength of the resulting cured product compared to when it is not added or when other water-soluble sodium salts are added. The curing accelerating effect of the water-soluble sodium salts increases as the amount added increases, and reaches a saturation point at a certain amount. The amount of the water-soluble sodium salts added is not particularly limited, as it varies depending on the mixing ratio of α-type tertiary calcium phosphate, dibasic calcium phosphate, and monobasic calcium phosphate, and the type of salt. 20% by weight based on the mixed powder material
It is preferably at most 30% by weight or less, and when contained in the curing liquid, it is preferably at most 30% by weight based on the curing liquid. Specifically, for example, α-type tertiary calcium phosphate,
Ca/P molar ratio with dibasic calcium phosphate is 1.4
To the mixed powder material of No. 8, 0.5% by weight of monobasic calcium phosphate was added to the mixed powder material, and 25% by weight of the mixed powder material was added.
When adding a curing liquid containing sodium succinate, curing can be performed in about 6 minutes.

In the present invention, in order to further improve the operability during kneading and the wettability of cement mud as desired, the hardening liquid may be added to
Furthermore, a water-soluble polymer can be contained. Preferred examples of the water-soluble polymer include polysaccharides, which are biopolymers, and polymeric surfactants. Specifically, examples include chitin, chitosan, soluble starch, glycogen, gum arabic, alginic acid, hyaluronic acid, cosidoroitin sulfate and salts thereof, polypropylene glycol, polyethylene glycol, polyvinyl alcohol, methylcellulose, carboxymethylcellulose, hydroxypropylmethylcellulose, etc. They can be used alone or as a mixture. The content of the water-soluble polymer can be used within a range from the minimum amount necessary to achieve the above object to the maximum amount that does not impair operability due to an increase in viscosity.

Furthermore, the hydraulic calcium phosphate cement composition of the present invention may contain, for example, quaternary calcium phosphate, hydroxyapatite, β-type tricalcium phosphate, alumina, in order to further improve biocompatibility and improve hardening properties. It is also possible to contain other ceramic powders such as.

Hydraulic calcium phosphate cement composition of the present invention**
For example, α-type tertiary calcium phosphate and
Calcium phosphate with a Ca/P molar ratio of 1.400 to
1-498 to obtain a mixed powder material, which may contain other ceramic powders as desired. Next, it can be obtained by adding monobasic calcium phosphate, or monobasic calcium phosphate and water-soluble sodium salts to the mixed powder material and/or hardening liquid. In use, a desired hardened product can be produced by adding a hardening liquid to a cement composition containing the mixed powder and kneading the mixture. At this time, the blending ratio of the cement composition and hardening liquid is
The ratio is preferably 1.0 to 2.5:1.

<Effects of the Invention> Since the hydraulic calcium phosphate cement composition of the present invention contains monobasic calcium phosphate as an essential component,
The Ca/P molar ratio of the mixed powder material is 1°470 to 1.49
Even if it is in the range of 8, it can be cured in a short time of 15 minutes or less. Furthermore, the present invention includes a mixed powder material obtained by mixing α-type tertiary calcium phosphate and dibasic calcium phosphate having a specific Ca/P molar ratio, and also contains the aforementioned dibasic calcium phosphate or dibasic calcium phosphate and water-soluble sodium salts. Therefore, it is possible to obtain a cured product that cures quickly at a pH around neutrality, has high strength, and has excellent biocompatibility, and can therefore be used as a composition for filling bone defects and bone voids. I can do it.

<Examples> The present invention will be described in more detail below with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

"1" L α-type tertiary calcium phosphate and dicalcium phosphate dihydrate (manufactured by Wako Pure Chemical Industries, Ltd.) at a Ca/P molar ratio of 1.
゜40.1.45.1.47, l, 48 or 1.498
Mixed so that

Then, 0.2% by weight for each day of the obtained mixed powder,
A cement composition was obtained by adding and mixing 0.5% by weight or 1.0% by weight of monobasic calcium phosphate, and 100 parts by weight of water was added to 200 parts by weight of the obtained cement composition and kneaded. At this time, the curing time was measured according to JIS R5201. Table 1 shows the measurement results of the curing time in relation to the Ca/P molar ratio and monobasic calcium phosphate content.The Ca/P molar ratio was the same as in Example 1 except that monobasic calcium phosphate was not added. A mixed powder material was prepared, a cured product was obtained, and a test was conducted. The results are shown in Table 1.

] 1 Town α-type tertiary calcium phosphate and tertiary phosphate calcium dihydrate (manufactured by Wako Pure Chemical Industries, Ltd.) were prepared at a Ca/P molar ratio of 1.
．． 48. Next, 0.5% by weight of monobasic calcium phosphate was added and mixed to the obtained mixed powder material to obtain a cement composition, and the obtained cement composition (
Hereinafter referred to as cement composition A)
2 each of water-soluble sodium salts such as sodium succinate, sodium milk, sodium acetate, or sodium chloride
It was cured using 100 parts by weight of a 5% by weight aqueous solution or water, and the curing time was measured according to JIS R5201. The results are shown in Table 2.

In addition, cement composition A was mixed with water, sodium succinate 25
It was cured using a wt % aqueous solution or a 25 wt % sodium lactate aqueous solution, and the obtained cured body was immersed in an artificial body fluid for 3 days and then taken out, and the compressive strength was measured in a wet state.

At this time, the cured body as a test piece was a cylinder with a diameter of 7 pus and a diameter of 14 pus, and a universal testing machine manufactured by Instron was used for the measurement.

The results are shown in Table 2.

(Blank below) 200 parts by weight of a mixed powder of μ'1 juice Uni 1 loss α type tertiary calcium phosphate and dibasic calcium phosphate dihydrate so that the Ca/P molar ratio was 1.45 was mixed with water. 100 parts by weight of a cured product (Test Example 1), a cured product obtained by curing 200 parts by weight of cement composition A produced in the same manner as Example 2 with 100 parts by weight of water (Test Example 2), Example A cured product obtained by curing 200 parts by weight of cement composition A produced in the same manner as in Example 2 using 100 parts by weight of a 25% by weight aqueous solution of sodium lactate (Test Example 3), 200 parts by weight of cement composition A produced in the same manner as in Example 2. The cured products (Test Example 4) obtained by curing 100 parts by weight of a 25% by weight aqueous solution of sodium succinate were each immersed in an artificial body fluid for 3 days, taken out, and dried. ” (manufactured by Rigaku Denki Co., Ltd.) to identify the reaction product. A chart showing the X-ray diffraction results of each cured product is shown in FIG.

As a result, it was found that the conversion to apatite progressed faster in (Test Example 2) than in (Test Example 1). By adding a small amount of monobasic calcium phosphate in this way, the C of tribasic calcium phosphate and dibasic calcium phosphate dihydrate is
If a mixed powder material with an a/P molar ratio of 1.48 can be cured in a practical curing time, a cement composition that is preferable from the viewpoint of biocompatibility can be obtained. Furthermore, it was also observed that when water-soluble sodium salts such as sodium lactate (Test Example 3) and sodium succinate (Test Example 4) were added, the conversion to apatite proceeded quickly.

[Brief explanation of the drawing]

FIG. 1 is a chart showing the X-ray diffraction of each cured product in test examples. 1. Cured body obtained in Test Example 1, 2. Cured body obtained in Test Example 2, 3. Cured body obtained in Test Example 3, 4.
- Hardened body obtained in Test Example 4, a... Maximum peak of α-type tertiary calcium phosphate, b... Maximum peak of apatite.

Claims (1)

[Scope of Claims] 1) A cement composition comprising a mixed powder material having a Ca/P molar ratio of α-type tertiary calcium phosphate and dibasic calcium phosphate of 1.400 to 1.498, and a hardening liquid, A hydraulic calcium phosphate cement composition characterized in that the mixed powder material and/or the hardening liquid contain monobasic calcium phosphate. 2) The hydraulic calcium phosphate cement composition according to claim 1, further comprising a water-soluble sodium salt in the mixed powder and/or hardening liquid.