JPH041123A - Sustained release material and production thereof - Google Patents

Abstract

PURPOSE:To provide the title material ensuring a drug to be sustainedly released over a long period of time by penetrating the drug impregnated in the central porous part through a laminate made up of a dense layer with a narrow releasing port, porous layer, a second dense layer with a narrow releasing port, successively. CONSTITUTION:The objective material to put to therapeutic use for affected sites by sustainedly releasing a liquid drug such as antibiotic or carbinostatic embedded near the affected sites in vivo and impregnated in advance, is so designed that the drug impregnated in the central porous part 1 is brought to a porous layer 4 through a releasing port 2 of the first dense layer 3 and then diffused and released externally through 1 second releasing port 5 of the second dense layer 6. With this means, the liquid drug is released through the regulated releasing port to the porous layer, from which the drug is then released through the regulated releasing port of the second dense layer; thereby, the releasing channel for the drug will become complicated along with the regulated releasing ports, leading to longer releasing time of the drug.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention is for treating the affected area by slowly releasing a drug solution such as an antibiotic or anticancer drug that is implanted in the vicinity of the affected area in a living body and impregnated in advance. The present invention relates to a sustained release material and a method for producing the same.

(Prior art) Conventionally, for the treatment of affected areas in vivo, such as the treatment of osteomyelitis, tumors, cancer, etc., sustained-release materials have been developed that allow antibiotics and anticancer drugs to be appropriately administered only to the affected areas. It has been devised.

Such sustained-release materials prevent the inconveniences that conventionally occur when administering the drug systemically, such as only a small amount of the dose acting on the affected area and the associated increase in side effects. Kadegu~ki.

As this type of technology, for example, Japanese Patent Application No. 57-20984
As described in No. 2, porous ceramics are impregnated with a medicinal solution and implanted into the affected area to supply an appropriate amount of the drug to the affected area.
As described in No. 9703, a technical means has been considered in which calcium phosphate with a large specific surface area is used as a base material, and a drug is adsorbed onto this material to be used as a sustained release material.

(Problems to be Solved by the Invention) However, conventional sustained release materials have a short release period for sustained release of impregnated drug solutions, and have had the problem that sufficient therapeutic effects cannot be obtained.

In other words, conventional sustained-release materials impregnate or adsorb a drug onto a substrate and then embed it in the affected area and then release the drug solution. It is being However, most drugs are not chemically adsorbed to the substrate, but are mostly physically adsorbed, so the release of the drug does not last for a long time. This is because it is difficult to control sustained release even if the pore size and porosity of porous ceramics are changed.

The present invention was made in view of the above-mentioned circumstances, and an object of the present invention is to provide a sustained release material that can maintain the release period of a drug solution over a long period of time and obtain a sufficient therapeutic effect, and a method for producing the same. do.

(Means for Solving the Problems) In order to solve the above problems, the present invention provides a sustained release material impregnated with a predetermined drug solution in advance and implanted in the vicinity of an affected area in a living body to sustainably release the drug solution. a first dense layer formed around the porous ceramic body and having holes or notches formed in a part of the porous ceramic body for releasing the chemical solution impregnated in the porous ceramic body; , a porous layer formed around this first dense layer,
The structure includes a second dense layer formed around this porous layer and provided with holes or notches that communicate the porous layer with the outside.

In addition, in order to create the sustained release material configured as described above, a foam slurry made by adding at least a foaming agent and water to ceramic powder is cast into a predetermined mold, dried, and made into a porous ceramic material. The first step is to create a porous ceramic body by heating wax to adhere it to a predetermined location of the ceramic porous body, then immersing it in a slurry for dense material made by adding at least an aqueous deflocculant solution to the ceramic powder, and then pulling it up. The slurry for dense material adhering to the periphery of the ceramic porous body is dried to form a first dense layer, and the attachment portion of the wax is formed as a hole or notch formed in the first dense layer. a second step; a third step of immersing the foam slurry in the foam slurry and then pulling it up to dry the foam slurry adhering to the periphery of the first dense layer to cover the porous layer; After heating the tip of the wax to adhere it to a predetermined location of the layer, it is immersed in the slurry for dense material, and then pulled up to dry the slurry for dense material adhering to the periphery of the porous layer to form a second dense material. and a fourth step of forming a hole or notch formed in the second dense layer to form a hole or a notch formed in the second dense layer.

(Function) By taking the above measures, the present invention allows the chemical solution impregnated into the porous ceramic body to be released from a regulated release port such as a hole or notch provided in the first dense layer, Then comes the porous layer. Then, the drug solution contained in this porous layer is slowly released from the release ports such as holes or notches in the second dense layer. Therefore, the release route for the drug solution is more complicated than in the conventional method, and the release port is also significantly regulated, resulting in a longer release time.

(Example) Examples of the present invention will be described below.

FIG. 1 is a sectional view of a sustained release material made of spherical ceramics according to an embodiment of the present invention. The sustained release material according to this example is made entirely of spherical ceramics, with a porous body part 1 impregnated with a drug solution formed in the center of its cross section, and a part of it surrounding this porous body part 1. A first dense layer 3 provided with an outlet 2 is coated. Further, the first dense layer 3 is covered with a porous layer 4 having the same chemical adsorption function as the porous body part 1, and the discharge port 2 is formed around the porous layer 4. A second dense layer 6 with outlet holes 5 formed at different locations is coated.

Next, a method for manufacturing the sustained release material configured as above will be explained with reference to FIG. 2.

In this example, a case will be described in which β-tricalcium phosphate (hereinafter referred to as "β-TCPJ"), which has excellent biocompatibility, is used as the base material.

First, 2.7 ml of foaming agent, 6 ml of foam stabilizer, and 1 ml of water were added to 30 g of β-TCP powder synthesized by mechanochemical method.
Add 2 ml and stir to mix to prepare a foamed slurry. Separately, 10 ml of a 10% deflocculant aqueous solution was added to 20 g of β-TCP powder synthesized by a mechanochemical method.
Add and mix to create a compact slurry.

Next, the foamed slurry is cast into a silicone rubber mold capable of forming a spherical molded product with a diameter of about 5 mm, dried, and taken out from the mold. As a result, the porous body portion 1 is formed. Next, as shown in FIG. 2(a), the porous body part 1
A rod-shaped wax 7 with a diameter of 1 mm is attached to a predetermined location by heating the tip of the wax. Then, the other end of the rod-shaped wax 7 is immersed in the slurry for dense materials, and immediately pulled up to coat the slurry for dense materials around the porous body portion 1, as shown in FIG. 2(b). Cover. After drying, the rod-shaped wax 7 is removed. As a result, the slurry for dense material becomes the first dense layer 3, and the portion of this dense layer 3 from which the wax 7 is removed becomes the discharge port 2.

Next, as shown in FIG. 2(c), the tip of a rod-shaped wax 8 is similarly attached to a predetermined location of the first dense layer 3 on the opposite side of the position where the discharge port 2 is formed. . and,
Holding the other end of the rod-shaped wax 8, it is dipped into the foamed slurry and immediately pulled up to cover the first dense layer 3 with the foamed slurry, as shown in FIG. 2(d). By drying this, the adhered foam slurry becomes a porous layer 4 and is covered.

Next, hold the other end of the rod-shaped wax 8 and dip it into the slurry for dense material to further coat the periphery of the porous layer 4 with the slurry for dense material, as shown in FIG. 2(e). By drying this, a second dense layer 6 is further formed. Then, by baking at 1100°C for 1 hour, the wax 7.8 is melted and the discharge ports 2.5 and 2.5 are respectively melted.
The slurry is sintered to produce the controlled release material shown in FIG.

The method of impregnating the material with the drug solution is to leave the sustained release material in the drug solution in a vacuum to allow it to soak into the drug solution.

According to the sustained release material manufactured in this way, the drug impregnated into the porous body part 1 in the center reaches the porous layer 4 through the release port 2 of the first dense layer 3, Furthermore, this chemical solution is diffused and released to the outside from the release port 5 of the second dense layer 6.

In this way, the discharge port 2°5 is connected to the first and second dense layers 3.
, 6, the amount of drug solution released can be suppressed and the release time can be maintained over a long period of time, compared to a sustained release material that uses a single porous substance. Therefore, sustained release over a long period of time is possible,
It is possible to achieve remarkable therapeutic effects that cannot be obtained conventionally.

In addition, since β-TCP is used as the base material, when the sustained release material of this example is implanted into bone tissue, especially for the treatment of osteomyelitis, the base material remains intact even after the drug is released. It combines with the bone and forms bone.

In addition, in the above embodiment, after impregnation with the chemical solution, if the release port 5 of the second dense layer 6 is closed with biological cement 9, the release of the drug solution during storage can be prevented, as shown in FIG. can be suppressed.

In addition, although the above example describes the case where β-TCP is used as the base material, other biocompatible materials such as hydroxyapatite, a complex of β-TCP and hydroxyapatite, calcium phosphate, alumina, zirconia, etc. Even if ceramics having properties are used, the same effects as in the above embodiment can be obtained.

Next, another embodiment of the present invention will be described with reference to FIGS. 4 and 5.

FIGS. 4(a) and 4(b) are cross-sectional views when the sustained release material according to this example is cut in the vertical direction (a) and the horizontal direction (b).

This controlled release material 20 has a porous portion 21 formed in the center, and a dense layer 22 formed around the porous portion 21 up to the region shown by the dotted line in the figure.

A plurality of convex porous portions 23 are formed on the surface of this dense layer 22 . Then, as the manufacturing process is shown in FIG. 5, a dense layer 24 is formed with rod-shaped wax 8 attached to the areas where each convex shape 23 gathers at a critical point. The porous layer 21.23 and the outside communicate with each other through openings 25.26.

That is, in this embodiment, the porous layer interposed between the first dense layer and the second dense layer is not formed over the entire spherical surface, but only on a portion of the spherical surface.

In this modified example, the impregnated chemical solution is released through the outer porous part 23, as in the above embodiment, so it has a shape that makes it even more difficult to release compared to the above embodiment, and the drug is gradually released over a longer period of time. release becomes possible.

(Effects of the Invention) As described in detail above, according to the present invention, it is possible to provide a sustained release material and a method for producing the same that can maintain the release period of a drug solution over a long period of time and obtain a sufficient therapeutic effect.

[Brief explanation of the drawing]

Figure 1 is a cross-sectional view of a sustained release material according to an embodiment of the present invention, Figures 2(a) to 2(e) are manufacturing process diagrams of the sustained release material, and Figure 3 is a cross-sectional view of a sustained release material according to an embodiment of the present invention. FIG. 4(a) is a longitudinal sectional view of another embodiment, FIG. 4(b) is a cross-sectional view of the same embodiment, and FIG. FIG. 5 is a diagram showing a specific manufacturing process of the same example. 1... Porous body part, 2.5... Outlet, 3... First
Dense layer, 4... Porous layer, 6... Second dense layer, 7°8... Rod-shaped wax. Figure 1 Figure 3 (a) (b) (C) Applicant's representative Patent attorney Jun Tsuboi Figure 2 (a) (b) Figure Figure

Claims (3)

[Claims] (1) In a sustained release material that is impregnated with a predetermined drug solution in advance and is implanted near the affected area in a living body to release the drug solution in a sustained manner, a ceramic porous body is impregnated with the drug solution, and a porous ceramic body is formed around the ceramic porous body. a first dense layer in which a part thereof is provided with an opening for releasing the chemical solution impregnated in the porous ceramic body; and a porous layer provided so as to cover the periphery of the first dense layer. 1. A sustained release material comprising: a dense layer; and a second dense layer that is provided to cover the porous layer and has an opening that communicates the porous layer with the outside. (2) Each of the ceramic porous body, the first and second dense layers, and the porous layer contains β-tricalcium phosphate, hydroxyapatite, a complex thereof, calcium phosphate,
The sustained release material according to claim 1, characterized in that it is made of either alumina or zirconia. (3) After casting a foam slurry made by adding at least a foaming agent and water to ceramic powder into a predetermined mold,
A first step of drying to create a ceramic porous body; After heating and adhering wax to a predetermined location of the ceramic porous body, a slurry for dense material created by adding at least an aqueous deflocculant solution to the ceramic powder. and then pulled up to dry the slurry for dense material adhering to the periphery of the ceramic porous body to form a first dense layer and to form the attachment portion of the wax on the first dense layer. a second step of forming holes or notches; and a third step of immersing the foam slurry in the foam slurry and then pulling it up to dry the foam slurry adhering to the periphery of the first dense layer to cover the porous layer. After heating and adhering the tip of the wax to a predetermined location of the porous layer, immersing it in the slurry for dense material, and then pulling it up and drying the slurry for dense material adhering to the periphery of the porous layer. second
without a dense layer of
a fourth step of forming holes or notches in the dense layer of the material.