JPH09625A - Implant transfuser - Google Patents

Abstract

PURPOSE: To provide an implant transfuser which is superior in affinity and adhesiveness with the living body as well as in sterilization and antibacterial performance. CONSTITUTION: A housing 1 with a liquid medicine reservoir is formed with a calcium phosphate type sintered compact (desirably with a hydroxyapetite sintered compact) with a relative denseness in excess of 95%. Consequently, bacterial infiltration is prevented by a dense calcium phosphate type sintered compact, sterilization and antibacterial performance are improved, and a satisfactory in vivo affinity and adhesiveness are obtained through the material of the sintered compact.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an infusion device for implanting and indwelling in a living body and percutaneously injecting a medicinal solution into the living body through the infusion device. It is applicable as an intestinal tract access device.

[0002]

2. Description of the Related Art Conventionally, a liquid medicine reservoir has been provided in a housing as an infusion device to be used by being embedded in a living body.
It is known to embed the housing in a living body and inject the liquid medicine into the living body via a liquid medicine reservoir in the housing. In this device, a recess for a chemical solution reservoir is provided in the housing, and the surface of this recess is covered with a self-sealing partition wall.
A catheter is connected to the drug solution reservoir for use.

By the way, the infusion device, particularly the housing, is embedded in the living body and left in place for a considerable period of time.
It is required to be stable in the long term and have good biocompatibility. From this point of view, as the material for the housing, for example, a polymer material such as PVC, fluororesin, polyethylene, polypropylene, polyurethane, polycarbonate, or polyether sulfone is adopted.
However, these materials cannot be said to have sufficient affinity and adhesiveness to tissues in the living body, and there is a problem that the placement position becomes unstable when the infusion device is left in the living body for a long time. Therefore, an improved technique has been proposed in which a calcium phosphate-based material is used instead of the above material, and the porosity of the material is adjusted to 5 to 60% to improve the adhesiveness to a living body by the anchoring effect (special feature. (Kaisho 63-46171).

[0004]

However, in the above-mentioned improved technique, there is the permeation of bacteria through the open pores, there is a risk that even bacteria inside the housing may not be sufficiently sterilized before implantation in the living body, and after implantation, If some kind of accident causes bacteria to be present in the surroundings, it may penetrate into the housing, eventually reach the reservoir, and be further transported to the inside of the living body through the catheter. There is also a problem that the strength of the housing itself is reduced due to the open pores.

In addition to the above-mentioned improvement technique, the publication proposing the above-mentioned improvement technique also proposes a method in which a material having a high porosity is used for the surface layer and a high-strength member is used for the inner layer. Even by this method, bacteria still infiltrate through the surface layer, and the sterilization and antibacterial properties are inferior. Furthermore, the connectivity between the surface layer and the inner layer is impaired, and bacteria may enter this gap. Further, since the strength becomes uneven between the surface layer and the inner layer, there is also a problem of poor durability, and in any case, it is not effective as a means for solving the above problems (improvement of sterilization property and antibacterial property).

The present invention has been made in view of the above circumstances, and has a good adhesive property with in-vivo tissue,
It is intended to provide an infusion device which can be stably placed in a living body for a long period of time and is excellent in sterilization and antibacterial properties.

[0007]

In order to solve the above-mentioned problems, a first invention of the present invention is to provide a liquid medicine reservoir for injecting a liquid medicine percutaneously by implanting it in a living body and leaving it in place for a predetermined period of time. Housing having a relative density of 95
% Of the dense calcium phosphate-based sintered body. A second invention is characterized in that, in the first invention, the calcium phosphate-based sintered body is made of a hydroxyapatite sintered body.

The relative density is represented by {bulk density / theoretical density (true density)} × 100%. In addition, it is desirable that the dense calcium phosphate has open pores on the surface that comes into contact with living tissue with a porosity of 1 to 4% (total porosity: also referred to as true porosity). The open pores are 0.5 μm
It is desirable to have a pore size of 50 μm, and therefore it is more desirable to define pore size in addition to porosity. The porosity has the same meaning as (100-relative density)%.

[0009]

That is, according to the present invention, since the housing is made of a dense calcium phosphate-based sintered body having a relative density exceeding 95%, it has uniform and high strength, and
It has an appropriate adhesiveness to the living body and can be placed in the living body stably in the long term. Further, since it is dense and has a limited number of open pores, it is possible to surely prevent bacteria from penetrating without being connected to the inside (reservoir) from the surface of the sintered body through the open pores. . Therefore, before embedding, bacteria do not penetrate deep inside the housing, and sterilization can be surely performed without any special method. Further, even if there is any accident after the implantation, the penetration of bacteria is blocked, and therefore the antibacterial property against the reservoir is also excellent. Where the relative density is 95
If it is less than or equal to%, continuous open pores are formed, the infiltration of bacteria is recognized, and the strength decreases, so the relative density was set to 95% or more.

The improved technique described above has a porosity of 5%.
It is assumed that the adhesiveness to a living body is reduced when the ratio is below. However, in a device that is left in the body for a long time like the indwelling infusion device of the present invention (for example, 4 weeks after the operation), a trace amount of Ca, P, etc., which is a characteristic of a bioactive material, and body fluid Ions contained in (Na ⁺ ,
By the reaction with K ⁺ , Ca ²⁺ , Mg ²⁺ , etc., a complex is intermediately formed, and the film becomes effective for the indirect bonding form between the soft tissue and the material. In the present invention, from such a viewpoint, sterilization while ensuring good adhesion to a living body by using a dense calcium phosphate-based sintered body,
Improving antibacterial properties.

The reasons for limiting the porosity, the pore diameter and the sintering temperature which are defined as desirable in the present invention will be described below. Porosity: 1 to 4% By ensuring the limited pores in the housing, bacteria can be prevented from permeating, good adhesion to the living body can be ensured, and good strength can be obtained. If the porosity exceeds 4%, the connectivity of the open pores is enhanced, and the penetration of bacteria is facilitated. Therefore, the upper limit is 4%. Further, if the porosity is less than 1%, the adhesiveness to the living body is deteriorated, so the lower limit is made 1%.

Pore size: 0.5 to 50 μm Open pores improve sterilization, antibacterial and adhesive properties by limiting the pore size in addition to the above porosity. here,
If the pore size is less than 0.5 μm, good adhesion to a living body cannot be secured, and if it exceeds 50 μm, penetration of bacteria is not sufficiently prevented, and sterilization and antibacterial properties are deteriorated. Limited to

[0013]

EXAMPLE Calcium hydrogen phosphate dihydrate [CaHPO ₄
2H ₂ O] was hydrolyzed in an alkaline aqueous solution to obtain a hydroxyapatite powder (calcium phosphate powder) having a calcium to phosphorus ratio (Ca / P) of 1.67. This powder had a particle size in the range of 0.5 to 10 μm and an average particle size of 1.5 μm. This powder was converted into 2 by CIP method.
It was pressed at 000 kg / cm ² and molded into a predetermined shape.
The obtained green compact was heated in air at 1150 ° C. for 1 hour to be sintered, and the obtained sintered body was finished as the housing 1. This housing 1 has a relative density of 98
%, The porosity was 2%, and the open pore diameter was about 1 to 20 μm.

Next, a self-sealing partition wall 3 made of silicon rubber was provided on the upper surface of the drug solution reservoir 2 of the housing 1, and a catheter 4 communicating with the drug solution reservoir 2 was connected to produce an infusion device (invention device). For comparison, the housing is made of an ultra-dense hydroxyapatite sintered body having almost no open pores and a porosity of 0.2%, and a hydroxyapatite sintered body having open pores of about 20% porosity. Using the housing, infusion devices for comparison (comparative devices 1 and 2) were produced.

When these infusion devices were sterilized with ethylene oxide gas, the invention device and the comparative device 1 of the ultra-dense housing were sterilized well, and no bacteria remained in the housing 1. In addition, when the bacteria permeation test was carried out in the same apparatus, the permeation of bacteria was not observed. On the other hand, in the comparative device 2, a small amount of bacteria remained inside the housing during sterilization, and it was also confirmed in the bacteria penetration test that the bacteria penetrate deep inside.

The above-mentioned infusion devices after sterilization were embedded in the living body 5, sutured to the living body 5 through the suture holes 6 and left in place for 30 days or 4 weeks. Not recognized, invention device and comparison device 2
Then, the housing 1 and the living body 5 are well bonded,
It was confirmed to have sufficient biocompatibility and adhesiveness.
For this reason, the housing 1 is indwelling and stable without moving in the living body 5, and the injection work from the skin 8 using the injection needle 7 can be easily performed. On the other hand, the comparative device 1 was found to be adhered to the living body, but was slightly inferior in adhesiveness to the above-mentioned invention device and the comparative device 2.

[0017]

As described above, according to the present invention, in a transfusion apparatus which is implanted in a living body and left in a predetermined period for percutaneously injecting a drug solution, a housing having a drug solution reservoir has a relative density of 95%. Since it is made of a dense calcium phosphate-based sintered body, it has excellent affinity and adhesiveness with living organisms, and also prevents bacteria from penetrating into the housing, resulting in good sterilization and antibacterial properties. If a hydroxyapatite sintered body is used as the calcium phosphate-based sintered body, better biocompatibility and adhesiveness can be obtained.

[Brief description of drawings]

FIG. 1 is a schematic view showing a usage state of an embodiment of the present invention.

[Explanation of symbols]

 1 Housing 2 Chemical Reservoir 3 Self-sealing Septum 4 Catheter 5 Living Body 6 Suture Hole 7 Injection Needle 8 Skin

Claims (2)

[Claims] 1. In an infusion device which is implanted in a living body and left in a predetermined period for percutaneously injecting a drug solution, a housing having a drug solution reservoir is a dense calcium phosphate-based sintered body having a relative density of 95% or more. In-vivo infusion device characterized by being formed 2. The in-vivo infusion device according to claim 1, wherein the calcium phosphate-based sintered body is formed of a hydroxyapatite sintered body.