JPH0528629B2 - - Google Patents

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. Regarding cement.

<Prior art> Hydraulic calcium phosphate cement is useful as a tooth and bone repair material because it is converted into a compound that resembles the main components of teeth and bones in living organisms through setting and hardening, and is also useful as a material for restoring teeth and bones. It is known to be useful as an adsorbent for molecules and harmful organic substances or inorganic ions in living organisms.

Conventionally, such hydraulic calcium phosphate cements have been made by using a combination of salts and dilute acids as the curing liquid (for example, Japanese Patent Application Laid-Open No. 59-88351), or using acidic acids containing unsaturated carboxylic acid polymers. solutions were used (for example, Japanese Patent Application Laid-open No. 60-1999)
Publication No. 253454). However, in such conventional hydraulic calcium phosphate cement,
Until the cement hardens, the hardening liquid is highly acidic and causes considerable irritation to living organisms. 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.

<Problems to be Solved by the Invention> Therefore, an object of the present invention is to provide a novel hydraulic calcium phosphate cement that does not cause irritation to living organisms, can be hardened in a relatively short time, and has excellent biocompatibility. It's about doing.

<Means for Solving the Problems> According to the present invention, a hydraulic calcium phosphate cement containing a mixed powder of quaternary calcium phosphate and monobasic calcium phosphate as a main component is provided.

The present invention will be explained in more detail below.

The hydraulic calcium phosphate cement of the present invention is
It is characterized by containing quaternary calcium phosphate and monobasic calcium phosphate as essential components.

The monobasic calcium phosphate used in the present invention reacts with water in the presence of an alkaline substance to produce dibasic calcium phosphate as shown in the reaction formula below,
It is a component that hardens cement.

Ca (H ₂ PO ₄ ) ₂・H ₂ O＋H ₂ O→CaHPO ₄・2H ₂ O
+H ₃ PO ₄ The generated phosphoric acid reacts with quaternary calcium phosphate, which is an essential component of the present invention, as shown in the reaction formula below to produce dibasic calcium phosphate, which quickly hardens the hydraulic calcium phosphate cement. .

Ca ₄ (PO ₄ ) ₂ O＋2H ₃ PO ₄ ＋7H ₂ O→4CaHPO ₄・
2H ₂ O In the above reaction, monobasic calcium phosphate and quaternary calcium phosphate react in an ideal manner, and depending on the composition of the cement, unreacted quaternary calcium phosphate may remain; Quaternary calcium phosphate acts as an aggregate to increase the strength of the cement.

The quaternary calcium phosphate used in the hydraulic calcium phosphate cement of the present invention can be obtained by decomposing dicalcium hydrogen phosphate dihydrate at about 500°C, for example.
Produces γ-type calcium pyrophosphate. Next, it is preferable to use quaternary calcium phosphate obtained by mixing the γ-type calcium pyrophosphate and calcium carbonate at a molar ratio of 1:2, calcining at about 1000°C, and then firing at 1350°C or higher. can. When used, it is desirable to crush the quaternary calcium phosphate and use it as a powder with a particle size of 100 mesh or less, preferably 325 mesh or less. As the primary calcium phosphate used in the hydraulic calcium phosphate cement of the present invention, commercially available products can be preferably used. Generally, commercially available products are monohydrated, but anhydrous forms can also be used.

In the present invention, the content ratio of the quaternary calcium phosphate and the monobasic calcium phosphate is Ca/p
The molar ratio is preferably 1.00 to 1.95. On this occasion
If the Ca/p molar ratio is less than 1.00, it is not preferable because the curing time becomes longer and the strength of the resulting cured product decreases. Moreover, if it exceeds 1.95, it is not preferable because the curing time will be long.

The hydraulic calcium phosphate of the present invention comprises the fourth
It can be obtained by mixing components containing calcium phosphate and monobasic calcium phosphate, and can be cured in about 20 to 100 minutes by simply mixing with water. Furthermore, since the hydraulic calcium phosphate cement of the present invention has a pH near neutrality, it does not irritate living organisms.

Furthermore, as a curing liquid for curing the hydraulic calcium phosphate of the present invention, water is sufficient as described above, but in order to improve the operability during kneading or filling into a living body, for example, polyethylene glycol, polyvinyl Examples include surfactants such as alcohol, lubricants such as glycerin, etc.
Particularly in view of affinity with living organisms, it is most preferable to contain polysaccharides. In general, polysaccharides are polymeric substances produced by living organisms, and are the main components of plants, seaweed, insects, crustaceans, etc., and are naturally found in the human body, so they have an affinity for living organisms. There is nothing wrong with gender. Specifically, preferred examples include compounds selected from the group consisting of chitin, chitosan, soluble starch, glycogen, gum arabic, alginic acid, chondroitin sulfate, hyaluronic acid, and mixtures thereof. When using, for example, chitin,
In the case of chitosan, it can be used by dissolving it 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 it in water. On the other hand, the aqueous solutions of alginic acid, chondroitin sulfate, and hyaluronic acid exhibit strong acidity, but by using them as salts, such as potassium salts, calcium salts, and sodium salts, they can be used in almost medieval conditions. Chondroitin sulfate salt has very good operability during kneading.
In addition, cement mud is particularly preferred because it exhibits good adhesion to hydroxyapatite, which is a major component of teeth and bones. 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, glycogen, gum arabic, alginic acid,
In the case of chondroitin sulfate and its salts, it is preferably 1 to 30% by weight, and in the case of hyaluronic acid and its salts, it is preferably 0.5 to 2% by weight. If the concentration of the polysaccharide is less than the above range, a sufficient effect cannot be expected, and if it exceeds the above range, the viscosity will increase, causing problems in operability, which is not preferable. The mixing ratio of the hardening liquid is hydraulic calcium phosphate cement.
The amount is preferably 0 to 60 parts by weight per 100 parts by weight.

The hydraulic calcium phosphate cement of the present invention is
It has good affinity for living organisms because its main component is a calcium phosphate compound that is similar to hydroxyapatite, which is the main component of living bones and teeth. Therefore, in the present invention, in addition to the above-mentioned essential components, ceramic powder or the like may be included 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 hydroxyapatite, fluoroapatite,
Examples include calcium phosphate compounds such as tertiary calcium phosphate and calcium pyrophosphate, which can be used alone or as a mixture.

Furthermore, the hydraulic calcium phosphate cement of the present invention can 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.

<Effects of the invention> The hydraulic calcium phosphate cement of the present invention has the following properties:
Since it contains quaternary calcium phosphate and monobasic calcium phosphate as essential components, it has excellent biocompatibility and can be cured in a practical amount of time. Further, when a polysaccharide is contained in the hardening liquid of the calcium phosphate cement of the present invention, appropriate consistency and good operability can be obtained during kneading. Moreover, even in narrow places and places with complicated shapes, it is possible to reliably and tightly fill the place, and to improve fluidity and leakage. Furthermore, if desired, a compound selected from the group consisting of barium sulfate, bismuth basic carbonate, iodoform, and mixtures thereof may be included in the cement of the present invention, thereby reducing X-ray radiation when the composition is cured. It can also improve contrast properties and impart antibacterial properties.

<Examples> The present invention will be explained in more detail by Examples below, but the present invention is not limited thereto.

Example 1 Quaternary calcium phosphate and monocalcium phosphate (manufactured by Wako Pure Chemical Industries, Ltd.) were mixed at a Ca/P molar ratio.
Hydraulic calcium phosphate cement was prepared by mixing at a ratio of 1.00, 1.33, 1.50, 1.67, and 1.95.

The tetracalcium phosphate used was first decomposed into γ-Ca ₂ P ₂ O ₇ by decomposing calcium hydrogen phosphate dihydrate (CaHPO ₄ 2H ₂ O (manufactured by Junsei Kagaku Co., Ltd.)) at 500°C. Calcium carbonate (CaCO ₃ (manufactured by Kanto Kagaku)) was mixed at a molar ratio of 1:2, calcined at 1000°C for 5 hours, and then fired at 1350°C for 6 hours. 6
Firing was carried out in two parts. That is,
First baked for 3 hours, then taken out and crushed.
Calcination was performed again for 3 hours to obtain a product consisting only of tetracalcium phosphate. Before use, it was ground until it passed through a 325 mesh sieve. Next, 60 parts by weight of water was added to 100 parts by weight of the obtained cement powder, and when the mixture was kneaded and hardened, the result was 20 parts by weight.
A cured product was obtained in ~100 minutes.

Example 2 Quaternary calcium phosphate and monocalcium phosphate (manufactured by Wako Pure Chemical Industries, Ltd.) prepared in the same manner as in Example 1 were mixed at a Ca/p molar ratio of 1.67,
A hydraulic calcium phosphate cement powder was prepared.

On the other hand, as a curing liquid, a solution of soluble starch, glycogen, and gum arabic (manufactured by Wako Pure Chemical Industries, Ltd.) each dissolved in water to make a 20% aqueous solution, and sodium alginate (manufactured by Wako Pure Chemical Industries, Ltd.)
Sodium hyaluronate (manufactured by Chitsuso) was dissolved in water to make a 5% by weight aqueous solution.
Sodium chondroitin sulfate (manufactured by Wako Pure Chemical Industries, Ltd.) dissolved in water to give a wt% solution
A 10% by weight aqueous solution was prepared by dissolving each in water. When the obtained cement powder and hardening liquid were kneaded at a weight ratio of 100:60, good consistency and operability were obtained in all combinations, and the hardening time was short at 20 to 100 minutes. .

Example 3 Cement powder and hardening liquid were mixed and kneaded in the same manner as in Example 2, except that a hardening liquid in which 0.5% by weight of chitosan (manufactured by Katakura Chitsukarin Co., Ltd.) was dissolved in a 1% by weight aqueous solution of citric acid was used. As a result, a good consistency was obtained and the curing time was short, about 20 minutes.

Example 4 In order to improve the X-ray contrast properties of each hydraulic calcium phosphate cement powder prepared in Example 1,
The cement powder 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 hardening solution 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 the hydraulic calcium phosphate cement prepared in Example 1 was similarly radiographed, it was not possible to identify the location where the cement was filled.

Example 5 In order to impart antibacterial properties, each of the hydraulic calcium phosphate cements 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 and formed into a cylindrical shape with a diameter of 3 mm and a height of 6 mm, and the cured product was tested immediately after curing, and after 1 day, 3 days, 7 days, and 30 days, as shown below. As a result, the cured product containing iodoform showed clear antibacterial properties and significantly inhibited the growth of all bacteria. Furthermore, the antibacterial effect was strongest immediately after curing and decreased over time.

Antibacterial test As test bacteria, Str.faecalis, Str.salivarius,
Five types of bacteria, Staph.epidermidis, B.subtilis, and E.coli, and a mixed culture derived from infected root canals were used. The concentration of bacteria was 1.2× according to the McFarland method.
The concentration was adjusted to 10 ¹² /ml in culture medium. Next, 0.1ml of the culture solution from each medium was evenly distributed into tryptone soya agar Petri dishes, dried at room temperature for 30 minutes, and then cultured under aerobic conditions at 37℃ for 48 hours to remove the cement. The bacterial growth inhibition zone to the nearest colony was measured.

Claims (1)

[Scope of Claims] 1. A hydraulic calcium phosphate cement containing as a main component a mixed powder of quaternary calcium phosphate and monobasic calcium phosphate. 2. The hydraulic calcium phosphate cement of claim 1, further comprising a compound selected from the group consisting of barium sulfate, basic bismuth carbonate, iodoform and mixtures thereof.