JP2847847B2 - Method for forming calcium phosphate-chitin composite film - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for forming a calcium phosphate-chitin composite film on the surface of a substrate, and is used particularly in the field of implant materials due to its excellent biocompatibility. Is what is done.

[Conventional technology]

Calcium phosphates, and among them, hydroxyapatite, are excellent in biocompatibility and have a large adsorptivity, and therefore various applications have been studied. In particular, research is actively being conducted on the replacement of living hard tissue or its use as an implant material for repair.

An implant material is required to have biomechanical strength in addition to biocompatibility. However, calcium phosphate itself is insufficient in strength with a sintered body. Therefore, forming a calcium phosphate film on the surface of a metal or ceramics or glass as a substrate or core material is considered most practically most promising.

Various methods have heretofore been proposed for forming a calcium phosphate film.

For example, JP-A-52-82893 discloses a plasma spraying method, JP-A-58-109049 discloses a sputtering method, and JP-A-51-111753 discloses a PVD method and a CVD method.
JP-A-128190 discloses an electrophoresis method, and JP-A-53-118411 discloses a coating method.

[Problems to be solved by the invention]

However, plasma spraying, sputtering, PVD
It is difficult to form a film on the surface of a substrate having a complicated shape such as the inside of a porous body in the CVD method and the CVD method, and a film is not formed on a non-conductive substrate in the electrophoresis method. There is a problem that.

The coating method is simple in operation, and JP-A-53-118411 discloses a method in which a fine powder of apatite is suspended in water, and this suspension is applied to the surface of a substrate, followed by baking. However, it is generally difficult to make fine powder into finer particles, and the adhesion strength of apatite to the substrate surface is difficult because of the presence of aggregated particles and the fact that dispersed particles are generally larger than 0.5 μm. However, it has a problem that it is weak and easily peels.

In the application method, there is a method in which a water-soluble polymer is made to coexist in a suspension of apatite fine powder, applied to the surface of a substrate, and fired to burn off the water-soluble polymer. This improves adhesion, but cannot be applied to materials that change at the firing temperature, such as titanium.

[Means for solving the problem]

In view of such circumstances, the present inventors have conducted intensive studies on a method of forming a film having high adhesion strength on a substrate without going through a firing step, and as a result, have found that a carboxymethylated chitin-allyl derivative (hereinafter referred to as A- Abbreviated as CM-chitin)
It was found that a film containing calcium phosphate was formed by forming a film in the coexistence of the compound and then insolubilizing the film, thereby completing the present invention.

That is, the present invention relates to calcium phosphate powder and A-CM-
An object of the present invention is to provide a method for forming a calcium phosphate-chitin composite film, which comprises applying a liquid film to the surface of a substrate with a slurry obtained by mixing a chitin methanol solution and irradiating the liquid film during or after drying.

Examples of the calcium phosphate used in the present invention include dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, hydroxyapatite, and mixtures thereof. These are produced by well-known methods such as a dry method and a wet method. Since the particle size affects the properties of the film, it is desirable not to include coarse aggregated particles, and a particle size of 10 μm or less is preferable.

A-CM-chitin, a synthetic method of which was discovered by one of the present inventors, is a derivative of chitin. Chitin is a type of mucopolysaccharide and is naturally abundantly present as a component of exoskeleton tissues such as crustaceans, insects, and shellfish.
However, at present the solubility and reactivity are poor and most are discarded. Therefore, various studies have been made for the purpose of functionalization, such as providing solubility by chemical modification.

Carboxymethylated chitin was synthesized by one of the present inventors and is described in Polymer Journa.
l, Vol. 15, p. 485-489 (1983). This has a structure in which the hydroxyl group at the C-6 position is partially carboxymethylated, and the degree of substitution changes from water-insoluble to water-swellable and water-soluble. It has been shown that those exhibiting electrolytic behavior and having a low degree of substitution act as cation exchange resins. Also,
Having particularly high adsorption capacity for Ca ²⁺ ion (Poly
mer Journal, Vol. 15, pp. 597-602 (1983)), having amino acid adsorption properties (Journal Macromolecular S
cience, Chemistry, A25, pp. 1427-1441 (1986)).

A method for further introducing an allyl group into carboxymethylated chitin has been found by one of the present inventors. This A-CM-chitin is obtained by substituting an allyl group for the hydroxyl group at the C-6 and C-3 positions, and thereby becomes soluble in methanol. In addition, the in vivo digestibility of carboxymethylated chitin is lost by allylation, but no toxicity has been found. The structural formula is as follows.

It has been clarified that those having an allyl group introduced also have a divalent metal ion adsorption ability. The concentration of the methanol solution of A-CM-chitin is difficult to clearly indicate because the methanol solubility differs depending on the degree of carboxymethylation and the degree of allylation, but is preferably about 1 to 15% by weight because the operation is easy. .

The mixing ratio of the calcium phosphate powder and the methanol solution of A-CM-chitin varies depending on the particle size of the calcium phosphate powder used. When a powder having a particle size of several μm is used, the ratio of calcium phosphate powder to A-CM-chitin is preferably in the range of 3: 1 to 0.01: 1. If the ratio is more than 3: 1, the fluidity of the slurry is impaired, which is not preferable. If the ratio is less than 0.01: 1, the effect of the presence of calcium phosphate is lost. When a fine particle having a particle size of 1 μm or less is used, the ratio of calcium phosphate powder to A-CM-chitin is desirably in the range of 0.2: 1 to 0.01: 1. 0.2: 1 powder
If the amount is larger, the chitin is adsorbed on the powder and becomes sediment as aggregated particles, which is not preferable. If it is less than 0.01: 1, the existing effect of calcium phosphate is lost.

The substrate used in the present invention may be any of metal, ceramics, glass and the like, but it is preferable to remove stains such as oils and fats with a solvent.

As a method of applying a liquid film to the substrate, a known method such as a coating method, a dipping method, and a spraying method can be used.

As a method of drying the liquid film, known methods such as natural drying, ventilation drying, and heat drying can be used, but usually 100 ° C. or less to avoid denaturation due to heat of chitin.
Preferably, a temperature of 40 ° C. or less is suitable.

The light irradiation during or after drying may be irradiation with visible light or ultraviolet light, and the illuminance of the irradiation light is sufficient as long as it is equal to or higher than the brightness of a room light, and irradiation with an ultraviolet lamp is preferable. This light irradiation leads to insolubilization of chitin.

〔Example〕

Hereinafter, the present invention will be described with reference to Examples, but the present invention is not limited thereto.

Note that “%” used in Examples means “% by weight”.

Example 1 A-CM-chitin (0.049 g) and methanol (1.1566 g) were placed in a glass tube having a diameter of 10 mm, and were well shaken to dissolve. A-CM-
The chitin concentration corresponds to 4.0%. 0.095 g of α-tricalcium phosphate powder (average particle size: 5 μm) was added thereto, and the mixture was shaken well to prepare a slurry.

Drop a part of this slurry on a glass plate,
After air drying for 3 days, the film was irradiated with light from an ultraviolet lamp for 2 hours. The weight of the formed film was 0.0008 g, and the thickness was 21 μm.

The glass plate with the film was immersed in 40 ml of a 3.3 × 10 ^-4 mol aqueous solution of calcium chloride, and no change was observed in the film when observed two days later.

Example 2 0.1066 g of A-CM-chitin was placed in a glass tube having a diameter of 10 mm, and 1.3123 g of methanol was added thereto and shaken well to dissolve. A-CM
-The concentration of chitin corresponds to 7.5%. Add 0.0044 g of hydroxyapatite powder (average particle size 0.3 μm) to this,
The mixture was shaken well to prepare a slurry.

Drop a part of this slurry on a glass plate,
After air drying for 3 days, the film was irradiated with light from an ultraviolet lamp for 2 hours. The weight of the formed film was 0.0007 g, and the thickness was 18 μm.

The glass plate with the film was immersed in 40 ml of a 3.3 × 10 ^-4 mol aqueous solution of calcium chloride, and no change was observed in the film when observed two days later.

Comparative Example 1 A slurry was prepared in exactly the same manner as in Example 1 except that A-CM-chitin was not used at all, and a part of the slurry was dropped on a glass plate. No film was formed after drying, and all were peeled off when immersed in 40 ml of a 3.3 × 10 ⁻⁴ aqueous solution of calcium chloride.

〔The invention's effect〕

ADVANTAGE OF THE INVENTION According to this invention, since the adhesion | attachment strength of a film | membrane is strong and a baking process is not required, it became possible to form a film | membrane also with the base material which has deteriorated at high temperature. The obtained film can be used for various applications, and is particularly useful for implant materials, adsorptive separation materials, and the like.

Claims (1)

(57) [Claims] 1. A calcium phosphate-chitin complex comprising applying a liquid film to the surface of a substrate with a slurry obtained by mixing a calcium phosphate powder and a methanol solution of a carboxymethylated chitin-allyl derivative, and irradiating the liquid film during or after drying. Method of forming a film.