JPH03128061A - Water-curable type 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 that can be used as a medical cement for filling bone defects and bone voids and a dental cement such as a tooth root canal filling material. Relating to cement compositions.

<Prior Art> Hydraulic calcium phosphate 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 by setting and hardening, and are also useful as materials for restoring teeth and bones. It is known to be useful as an adsorbent for harmful organic substances or inorganic ions in living organisms.

Conventionally, such hydraulic calcium phosphate cement compositions have been prepared by using a combination of salts and dilute acids as a curing liquid (for example, Japanese Patent Application Laid-Open No. 59-88351),
Further, an acidic solution containing an unsaturated carboxylic acid polymer has been used (for example, Japanese Patent Application Laid-Open No. 60-253454). However, in such conventional hydraulic calcium phosphate 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 hardened, the pH decreases due to the elution of unreacted acids, resulting in the problem of irritation to living organisms.

To solve this problem, hydraulic calcium phosphate 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 hydraulic calcium phosphate cement compositions that harden with water have been developed to date.1 For example, a hydraulic calcium phosphate 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 hydraulic calcium phosphate cement composition has an approximately neutral pH and is less irritating to living organisms, thus solving the problems of conventionally known hydraulic calcium phosphate cement compositions.

However, the above-mentioned hydraulic calcium phosphate cement composition has a disadvantage in that it takes on a so-called wet sand-like appearance when mixed with water, and has poor operability. That is, if there is too little water, the mud will become unkempt, and if there is too much water, it will be difficult to transport the mixed mud. Furthermore, since the fluidity of the mixed mud is poor, it is difficult to fill narrow spaces or places with complicated shapes.

In addition, in order to adjust the consistency and wettability of the mixed mud during mixing of hydraulic calcium phosphate cement, a water-soluble polymeric surfactant such as polyethylene glycol or polyvinyl alcohol is added to the hardening liquid of the cement. However, when the polymeric surfactants and the like are used in cement that is applied to living organisms, there is a problem with biocompatibility, and in the case of polyethylene glycol, although the consistency during kneading is good, A drawback arises in that the time required for curing is as long as 60 minutes or more. Furthermore, although polyvinyl alcohol can improve wettability and surface activity, it has the drawback of insufficient consistency during kneading.

<Problems to be Solved by the Invention> Accordingly, an object of the present invention is to provide a novel hydraulic calcium phosphate cement composition that can obtain an appropriate consistency and good operability during kneading.

Another object of the present invention is to provide a novel hydraulic calcium phosphate cement composition having sufficient fluidity and wettability so that even narrow spaces or places with complex shapes can be reliably and tightly filled. It is about providing gifts.

Still another object of the present invention is to provide a novel hydraulic calcium phosphate cement composition that can be cured in a relatively short time and that allows the curing time to be arbitrarily selected as required. be.

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 dihydrate is 1.
．． 200 to 1.498 as a main component, and the curing liquid of the composition contains at least a water-soluble polysaccharide. provided.

The present invention will be explained in more detail below.

The hydraulic calcium phosphate cement composition of the present invention is characterized by containing a specific cement composition and a hardening liquid containing at least a water-soluble polysaccharide.

The cement composition used in the present invention contains α-type tribasic calcium phosphate and dibasic calcium phosphate dihydrate in a Ca/
This is a composition obtained by mixing P in a molar ratio in the range of 1.200 to 1.498. If the Ca/P molar ratio is outside the above range, it will be in a neutral region and cannot be cured within a practical time, and the strength of the resulting cured product will not be practical. It needs to be within.

In the hydraulic calcium phosphate cement composition of the present invention,
In addition to the cement composition, a hardening solution containing at least a water-soluble polysaccharide is used. It is a main component of insects, crustaceans, etc., and is naturally also contained in the human body, so there is no problem with its affinity for living organisms. The water-soluble polysaccharide used in the present invention has excellent biocompatibility, provides sufficient consistency during kneading, improves wettability during kneading, and further improves the hardening time of the hydraulic calcium phosphate cement composition. Preferable examples include compounds selected from the group consisting of chitin, chitosan, soluble starch, glycogen, gum arabic, chondroitin sulfate, hyaluronic acid, and mixtures thereof. Can be done. When used, for example, chitin and chitosan can be dissolved in an aqueous solution containing an organic acid such as citric acid, malic acid, or lactic acid, and other polysaccharides can be used by simply dissolving them in water.

On the other hand, the aqueous solutions of chondroitin sulfate and hyaluronic acid exhibit strong acidity, but by using them in the form of salts such as potassium salts, calcium salts, and sodium salts, they can be used in a neutral state, and moreover, they can be used in a neutral state. Chondroitin sulfate salt has very good operability during kneading, and cement mud exhibits good adhesion to hydroxyapatite, which is the main component of teeth and bones, and furthermore, it is effective in hardening hydraulic calcium phosphate cement compositions. This is particularly preferred since the time can be kept within 10 minutes. The concentration of the water-soluble polysaccharide in the hardening solution varies depending on the type of polysaccharide, but for example, 1 to 10% by weight for chitin and chitosan, soluble starch,
It is preferably 1 to 30% by weight in the case of glycogen, gum arabic, chondroitin sulfate and its salts, and 0.5 to 2% by weight in the case of hyaluronic acid and its salts. If the concentration of the polysaccharide is less than the above range, sufficient effects cannot be expected, and if it exceeds the above range, the viscosity will increase, causing problems in operability, which is not preferable.

In the present invention, as a compound that can be contained in the curing liquid in addition to the water-soluble polysaccharide, for example, a surfactant such as polyethylene glycol or polyvinyl alcohol can be used, and further improves the operability. A lubricant such as glycerin can also be added for this purpose.

The mixing ratio of the hardening liquid is preferably 0 to 30 parts by weight based on 100 parts by weight of the cement composition.

The hydraulic calcium phosphate cement composition of the present invention uses a calcium phosphate compound similar to hydroxyapatite, which is the main component of living bones and teeth, and a water-soluble polysaccharide as essential components, so it has an affinity for living organisms. is good. Therefore, in the present invention, in addition to the above-mentioned essential components, ceramic powder or the like may be added to improve mechanical strength and biocompatibility when the composition is cured, as long as it does not impair biocompatibility. etc. can also be improved. Examples of the ceramic powder include calcium phosphate compounds such as hydroxyapatite, fluoroapatite, β-type tertiary calcium phosphate, calcium pyrophosphate, and quaternary calcium phosphate, which can be used alone or as a mixture.

Furthermore, the hydraulic calcium phosphate cement composition of the present invention may optionally contain an X-ray contrast agent, an antibacterial agent, etc., if necessary. For example, preferred X-ray contrast agents may be selected from the group consisting of barium sulfate, bismuth basic carbonate, iodoform, and mixtures thereof. Preferred antibacterial agents include iodoform and chlorhexidine. The amount of the X-ray contrast agent or antibacterial agent used is not particularly limited, but is preferably 0 to 30 parts by weight per 100 parts by weight of the hydraulic calcium phosphate cement composition.

The hydraulic calcium phosphate cement composition of the present invention can be easily hardened by mixing and kneading the cement composition and the hardening liquid.

<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.

JLIL α-type tertiary calcium phosphate and dibasic calcium phosphate 2
hydrate and the Ca/P molar ratio is 1.200.1.3
30.1.470.1.498 by mixing in a ball mill to prepare a cement composition. Next, as a hardening liquid for the cement composition, sodium chondroitin sulfate (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in water to prepare a hardening liquid containing 1.10.30% by weight of sodium chondroitin sulfate. When 1.5 parts by weight of the obtained cement composition was mixed with 1 part by weight of each of the hardening liquids, a good consistency was obtained and the operation was much easier than when mixing with water alone. The bag has improved.

Loss of Mind Summer Solstice α Type Tertiary Calcium Phosphate and Dibasic Calcium Phosphate 2
Hydrate (manufactured by Wako Pure Chemical Industries, Ltd.) and Ca/P
They were mixed at a molar ratio of 1.450 to prepare a cement composition. Next, as a hardening liquid for the cement composition, sodium chondroitin sulfate (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in water to prepare hardening liquids containing 10% to 30% by weight of sodium chondroitin sulfate, respectively. When 1.5 parts by weight of the obtained cement composition was mixed with 1 part by weight of each of the above-mentioned hardening liquids, a good consistency was obtained, and when the curing time was measured, the curing time was 10 to 25 minutes. It hardened in such a short time.

Both 10L polyethylene glycol (manufactured by Wako Pure Chemical Industries, Ltd.,
The cement 1-composition and the curing liquid were mixed and kneaded in the same manner as in Example 2, except that a curing liquid in which 10.3° (molecular weight: 6,000) and 50% by weight of a compound (molecular weight: 6,000) was dissolved in water, respectively, was used. As a result, when a curing liquid containing 10% by weight of polyethylene glycol was used, good consistency and operability could not be obtained.

Furthermore, when a curing liquid containing 30.50% by weight of polyethylene glycol was used, the curing time was 70 minutes, respectively.
It took a long time, 100 minutes.

A mixture of sodium chondroitin sulfate and polyethylene glycol (manufactured by Wako Pure Chemical Industries, Ltd., molecular weight 6000) was used as the curing liquid at the blending ratio shown in Table 1, but in the same manner as in Example 2. When the cement composition and hardening liquid were mixed and kneaded, good consistency and operability were obtained. Table 1 also shows the results of measuring the curing time.

Table 1 α-type tertiary calcium phosphate and dibasic calcium phosphate 2
hydrate (manufactured by Wako Pure Chemical Industries, Ltd.).

Mix so that the Ca/P molar ratio is 1.450,
A cement composition was prepared. Next, the hardening liquid of the cement composition is a solution of soluble starch, glycogen, and gum arabic (manufactured by Wako Pure Chemical Industries, Ltd.) each dissolved in water to make a 200 weight aqueous solution, and 1% by weight of hyaluronic acid. Each solution dissolved in water was prepared as MM. When the obtained cement compositions and the respective hardening liquids were mixed and kneaded, all the hydraulic calcium phosphate cement compositions showed good consistency. Also, the curing time is 30
It was a short time, about a minute.

A cement composition and a hardening liquid were mixed in the same manner as in Example 4, except that 1% by weight of chitosan (Katakura Chikkarin Co., Ltd. 1) was dissolved in a 1% by weight aqueous solution of citric acid as a hardening liquid. When kneaded, a good consistency was obtained and the curing time was 1.
It was a short time, about 5 minutes.

In order to improve the XB contrast properties of each hydraulic calcium phosphate cement composition prepared in Example 1.

The cement composition further contained 30 parts by weight of each of barium sulfate, basic bismuth carbonate, and iodoform (Wako Pure Chemical Industries, Ltd.) based on 100 parts by weight of the composition. The resulting composition was then kneaded with a curing liquid to form a paste, and the paste was filled into the root canal of a human tooth that had undergone pulp removal treatment. After the paste had hardened, X-ray photography was performed, and the cement-filled areas were clearly seen.

When X-ray photography was similarly performed on the hydraulic calcium phosphate cement composition prepared in Example 1, it was not possible to identify the location where the cement was filled.

In order to impart antibacterial properties, each hydraulic calcium phosphate cement composition prepared in Example 1 contained 30 parts by weight of iodoform based on 100 parts by weight of the composition.

Next, the obtained composition was kneaded with a curing liquid, molded into a cylindrical shape with a diameter of 3 volumes and a height of 6 mm.
The following test was conducted on the cured product after 1 day and 30 days. As a result, the cured product containing iodoform exhibited clear antibacterial properties and significantly inhibited the growth of all bacteria. Furthermore, the antibacterial effect was strongest immediately after curing and decreased over time.

As the five-genus faecalis test bacteria, Str, faecalis, Str, 5
alivarius.

5taph, epidermidis, B, 5ubti
Five types of bacteria, Lis, E. and coli, and m1xed culture derived from infected root canals were used. The concentration of bacteria was 1.2 x 10”/m according to the McFarland method.
Q. prepared in culture medium. Next, remove 0.1 of the culture solution from each medium.
Tryptone 5 oya aga equally in mQ each
After drying at room temperature for 30 minutes, the mixture was cultured at 37° C. for 48 hours under aerobic conditions, and the bacterial growth inhibition zone from the hardened cement body to the nearest colony was measured.

<Effects of the Invention> The hydraulic calcium phosphate cement composition of the present invention comprises α-type tertiary calcium phosphate having self-hardening ability and secondary calcium phosphate.
Calcium phosphate dihydrate is mixed with a specific Ca/P molar ratio, and the curing liquid contains at least a water-soluble polysaccharide, so it has an appropriate consistency and good operation for M-harmony. You can get sex. Furthermore, even in narrow places and places with complicated shapes, it can be filled reliably and tightly, and has good fluidity and wettability. Further, the curing time is relatively short, and the curing time can be arbitrarily selected by adjusting the type and amount of polysaccharide. If desired, the composition of the present invention may further contain a compound selected from the group consisting of barium sulfate, basic bismuth carbonate, iodoform, and mixtures thereof. It can also improve X-ray contrast properties and impart antibacterial properties.

Claims (1)

[Scope of Claims] 1) A cement composition containing as a main component a mixed powder of α-type tribasic calcium phosphate and dibasic calcium phosphate dihydrate with a Ca/P molar ratio of 1.200 to 1.498. 1. A hydraulic calcium phosphate cement composition, wherein the hardening liquid of the composition contains at least a water-soluble polysaccharide. 2) The hydraulic calcium phosphate cement composition of claim 1, wherein the cement composition further contains a compound selected from the group consisting of barium sulfate, basic bismuth carbonate, iodoform, and mixtures thereof.