JPS6092768A - Living body terminal - 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 The present invention relates to a bioterminal whose main part is made of a ceramic material whose main raw material is tricalcium phosphate and/or tetracalcium phosphate.

Conventional percuLaneous electLrode
connector (terminal with transcutaneous electrode) and ca
A biological terminal such as nnula (intubation) has one end on the skin of the living body and the other end buried under the skin, and has an electrical terminal that is used to count various biological information such as blood pressure, blood flow rate, temperature, and electrocardiogram signals. It is used as a terminal or as an inlet for injecting infusions, various medicinal solutions, etc., or for extracting and injecting blood flow for artificial kidney dialysis, etc. through its through-hole, and is mainly used for so-called so-called silicone rubber, fluorinated fat, etc. Those made of bioinert materials have already been proposed.

However, these are not just foreign substances to the living body, and the part where they are attached to the living body is left in a state of trauma, so they cannot withstand long-term use due to bacterial infections etc. from the gap between the two. Not only is it impossible to obtain, but it is also inferior in fixation to the body, so there is a risk of bleeding due to shaking, or when extracting bioelectrical signals such as electrocardiogram signals, it is impossible to eliminate noises such as so-called Arch 7 AcF. This method has several problems, such as a lack of stable retrieval of biological information, so it has not yet been widely used.

On the other hand, in recent years, the excellent biocompatibility and osteoinductivity of calcium phosphate compound sintered bodies have been elucidated, and the use of these sintered bodies for artificial tooth roots and artificial bones has been proposed and put into practice. The physiological reactivity of the bodies with skin tissue is completely unknown in the prior art.

In view of the above, the present inventors conducted intensive research and surprisingly found that ceramic materials whose main raw materials are tricalcium phosphate and/or tetracalcium phosphate not only have an affinity for skin tissue. The present invention was arrived at by discovering the fact that it joins tightly and integrally with these tissues.

Hereinafter, the bioterminal of the present invention will be discussed, including its material composition, manufacturing method, shape and structure, and modes of use.

Particle composition/manufacturing method In the present invention, "ceramic material" refers to a sintered material whose main raw material is tricalcium phosphate and/or tetracalcium phosphate, or a support material such as metal or ceramic that is thermally sprayed or It is a coating material made of sintered coating 1), and in order to improve its sinterability, strength, porosity, etc., it is coated with M g Or Na
20 r K 20 r Ca F 21 A I
20s + S! 021CaO,Fe2O,,M
nO, MnO□wZnO, C, SrO, PbO, BaO
.

It also includes mixtures of various additives such as T i O2 and Z r O2.

On the other hand, examples of manufacturing methods include a so-called sintering method for a single body or a base material such as a metal, and a plasma spraying method for a base material such as a metal. A raw material consisting of tricalcium acid or tetracalcium phosphate is molded using a mold or a rubber press, etc.
It is obtained by compression molding into a desired shape under a pressure of about 0 k8/can" and then sintering it at a temperature of about 7 K8/can", but the manufacturing method and For more details including the composition, refer to the following known techniques.

That is, JP-A-55-140756. Same 55-4224fl Same 55-56 (1G2. Same 54-!J45] 2 Same 5
6-18864. 56143156 56-16
6843. 53-2', 3997 53-752
09. Japanese Patent Publication No. 533 (Japanese Patent Publication No. 583', ) 533 In addition, the phase density of the sintered phase and coating material (based on the density of tricalcium phosphate) which is particularly useful in the present invention from the viewpoint of bondability with skin tissue. is about 6() to 99.5%, more preferably about 85 to 95%.

Shape and Structure The bioterminal configuration of the present invention can be made into a desired shape depending on the purpose of use. Typical examples thereof will be explained in detail below with reference to the accompanying drawings fτj.

That is, FIG. 1 is a cross-sectional view showing one example of the living wood terminal of the present invention, and in the figure, a living wood terminal I used as an electrical terminal is shown.
The terminal head part 2 and the bottom part 3 are made of a ceramic material whose main raw materials are tricalcium phosphate and/or tetracalcium phosphate. A conductive member 4 such as gold wire, silver wire, platinum wire, alloy wire, carbon fiber, etc. is buried therein for electrically connecting the terminals, and an arbitrary number of suture holes 5 are drilled in the terminal bottom 3 as required. ing.

The biomedical terminal l of the second structure is used with the terminal bottom 3 buried and fixed under the skin, and the upper end of the terminal head 2 protruding subcutaneously, and is used for extracting bioelectrical signals, etc., or for connecting pacemakers, etc. Used as an electrical terminal for biological electrical stimulation.

Similarly, FIG. 2 is a cross-sectional view showing an example of the biological terminal of the present invention used as a biological plug, and this biological terminal (2) has a through hole 6 in place of the conductive member 4 for communicating between the inside and outside of the living body.
It has the same configuration as the previous example except that it has (in the figure, the same reference numerals refer to the same parts as in the previous example).

On the other hand, since the ceramic material of the present invention can achieve the desired purpose by intervening in the part that comes into contact with the skin tissue, only the main part of the bioterminal is made of a sintered body, and the pond is made of a synthetic material + a different material such as J4 resin. It may be constructed of a shrine, or the main part thereof may be made of a ceramic coating material whose main raw material is tricalcium phosphate and/or tetracalcium phosphate (Japanese Patent Application Laid-Open No. 53-28'
, J 97, 752 (+9. and Special Publick No. 1983 39)
533, etc.).

For example, the minute side formed by forming a sprayed or sintered layer of tricalcium phosphate and/or tetracalcium phosphate on the outer periphery of the minute metal side can be used as an electrical bioterminal.

FIG. 3 is a cross-sectional view of the micro-sword-shaped bioterminal (2), in which a sintered coating layer mainly made of tricalcium phosphate and/or tetracalcium phosphate is coated on the outer periphery of the metal base 17 made of gold T1 or the like. It is formed by forming a layer 8, and is used by simply piercing and fixing it to the patient's skin.

Furthermore, as shown in Fig. 4, outside 1 of 5 metal pipes such as brass pipes
A structure of a bioterminal in which a sintered coating NlO containing tricalcium phosphate and/or tetracalcium phosphate as a main component is formed on ^1, and a through hole as a chemical liquid conduction path and a metal tube as a conductive member are combined. can be obtained.

As is clear from the above, the bioterminal of the present invention can take various shapes, structures, and dimensions, and is not limited to a specific form.

Toyohi Shijiri As mentioned above, the bioterminal made of a ceramic material based on tricalcium phosphate and/or tetracalcium phosphate according to the present invention is not only biocompatible, but also has an interface with skin tissues such as the epidermis and dermis. It has been revealed that it can be bonded and stably fixed to living bodies, so it can be used, for example, as a terminal for connecting an external power source to a cardiac pacemaker, or as a hole for hemodialysis, and even has an ultrasonic detection device at its tip. It is said to be extremely useful in the field of diagnosis and treatment, or in the field of animal experiments, as it is widely used as a terminal for connecting in-vivo conductors with various sensor elements such as sensors and external measuring instruments. obtain.

In addition, bioterminals with a through-hole structure can be widely used as drug input ports in various drug delivery systems, and when used, they can be embedded in the skin,
It is sufficient to simply connect a fixed (implanted) biological terminal with a tube or the like for quantitatively feeding a drug solution driven by a micro pump or the like.

Here, as a particularly useful mode of use of the bioterminal of the present invention,
It can be used as an inlet for so-called iontophoresis (iontophoresis) in which drugs are driven electrochemically.

For example, in place of the conventional injection of insulin/IICl in an artificial pancreas (which was performed using a micrometer injection pump), the present invention's implant terminal is used to simply inject the anode of the DC power supply. Insulin canone can be introduced into the body very easily and safely only by conjugating the insulin kanone.

Why? Normally, iontophoresis is performed from the skin, but in that case, it is only the stratum corneum of the skin or the electrical layer that acts as a physical barrier layer, and the introduction of relatively thick molecules such as insulin. Although it was difficult, with the bioterminal of the present invention, the stratum corneum of the skin becomes a barrier and there is no impedance and material Jli (fJ 41L JA:
This results in a moderate decrease in the current value (normally, in the case of instant IJ, a few μl to several 11
1) Within the range of \) 12) The constant wind or) can be easily achieved by feedback injection by Guruleaf-human sensor.

That is, the bioterminal of the present invention can be used for iontophoresis.
When using conventional iontophoresis, a chemical solution can be injected into the implant bio-terminal instead of the chemical solution-impregnated conductor (the shell consists of a water retention shrine such as a sponge or cotton pad, and the shell consists of a hydrophilic gel). The guides χ are connected to form a seki conductor, and the disjunction conductor made of various well-known bioelectrodes (for example, Japanese Unexamined Patent Publication No. 58-110066 or Japanese Patent Application No. 56-106935, reference 11u) is connected to a skin pond. Paste it on the spot t, and apply a direct current between the two (if it is an ionic drug or a cation) (!
It is sufficient to pass through (return, etc.).

For details of the iontophoresis itself, please refer to the statement in the publication.
Ii look at C! It will be 1u.

Hereinafter, the present invention will be described in detail with reference to Examples.

Example 1 1. Production of bioterminal A synthetic powder of tricalcium phosphate was filled into a mold, and the diameter was 0.
．． 800 kg/ca with 05+nIn gold wire
n2) King horn is used to form l-shaped wires and the bulk density is 1.6g/Cl.
113 green compacts were obtained. Cut this into the shape of the terminal head (see Figure 1) using a lathe and a dental Guyamon 1ζ ('-).
processed. Similarly, the synthetic powder was filled into a mold together with a thin gold wire, compression molded, and cut to form a terminal bottom part b (see FIG. 1). Next, the thin gold wires of the side-pressed powder were joined, and a del-shaped anode (tight powder), which had been thoroughly kneaded in a mortar with water added between them, was applied and bonded. This was heated at 1,200°C for 1 hour
', 11 sintering process compressive strength 4 + 300 kHz/
Cm2.11b1 each has an insect intensity of 1. + 000 kg/
Can 2, relative density 93%, adhesive part 1 uniformly sintered, one bioterminal as shown in FIG. 1 was placed.

22-2, the bottom of the terminal has a diameter of 201111111, a thickness of 2+n+n, and a diameter of the head and neck part of the terminal is 5 m+a. , Sutra (
As a result of 1 pt observation, the terminal was strongly bonded to the skin tissue in the 2nd week at the bottom and neck part, and even when pulled, it was in a state where the length was less than 1%, and even after 1 year, it was not visible to the naked eye. No abnormal findings such as 1 or Enzan Y reaction were observed.

In addition, inflammatory cells were also found in normal histological searches.
I couldn't.

On the other hand, a silicone film of the same shape was used as a control.
There was no adhesion to the skin even 4 weeks after the surgery, and inflammatory redness was observed. Also, 2 months 1
The inflammation progressed and began to suppurate, and fell off in the third month.

Example ■ M2O0, as an additive to the tricalcium phosphate powder,
8%, Na20 1, 8%, K, OO, 2% and C
Excluding the point that a mixed powder containing 2% of aFe fl was used as the starting H material, 1 pull] Soil! 'l'I n' (Similar to 91j, a small circle containing a brass tube with a diameter of 1 m + n &'i (
A book (tato diameter: 31111111) was manufactured and polished to a polishing width to obtain a microtubular terminal having the shape shown in attached Figure 4.

The length of the sintered part of this terminal is 8 ml +, outer diameter 2 m
“It was 1.

Next, this terminal was punctured and buried in the film-formed chest so that its tip was located subcutaneously, and after about 3 weeks, it was completely joined and fixed to the skin tissue.

Therefore, we connected the end of the terminal to a conduit filled with physiological saline and measured the DC resistance. (using a bond), the value of Ω was obtained at 3.6. Compared to the normal skin resistance through the stratum corneum, which is approximately 100Ω, a remarkable decrease in resistance is observed.

Example III Tricalcium phosphate 70% by weight, Tetracalcium phosphate 3
Both were mixed at a ratio of 0% by weight, and this was molded into the shape of a terminal @ part and a terminal bottom part in the same manner as in Example 1, and bonded.

This was sintered at 1,250° C. for 1 hour to obtain a bioterminal as shown in FIG.

Next, animal experiments similar to those in Example 1 were conducted on this bioterminal, and results substantially equivalent to those in the previous example were obtained.

A thin gold wire with an inner diameter of 0.05 mm is used as a core material, and a coating layer of tricalcium phosphate is formed on the surface by plasma spraying. After baking this at 1200°C for 10 minutes, it is polished in an abrasive. Then, 1q of micro ZJ-61 shaped bioterminals as shown in Fig. 3 were obtained.

Next, animal experiments similar to those in Example U were conducted on this bioterminal, and substantially the same results were obtained.

Example V Ca 3(]) as an additive in tetracalcium phosphate powder
○, )27%, Mg0 0.8%, Na2O1.8%,
A coating layer of tetracalcium phosphate with a gold wire of diameter (1,95+n+n as the core material) was prepared in the same manner as in the previous example except that a mixed powder containing 0.2% K2O and 20.2% CaF was used as the starting material. was formed, fired, and then polished with an abrasive material to obtain a microtubular terminal having the shape shown in the attached FIG. 3.

Animal experiments similar to those in the previous example were conducted for this bioterminal, and almost the same results were obtained.

[Brief explanation of the drawing]

Attached Figures 1 to 4 are schematic cross-sectional views of the bioterminal of the present invention. 2... Terminal head, 3... Terminal bottom, 4... Conductive member, 5... Suture hole, 6... Through hole. Patent applicant: Advance Development Institute Co., Ltd. Figure 1 Figure 2 Figure 4

Claims (3)

[Claims] (1) At least the part in contact with the skin tissue is made of a ceramic material whose main raw material is tricalcium phosphate and/or tetracalcium phosphate as an epidermis-friendly component, and has conductivity for electrically connecting the inside and outside of the body. A biological terminal characterized by having a member. (2) At least the part that contacts the skin tissue is made of a ceramic material whose main raw material is tricalcium phosphate and/or tetracalcium phosphate as an epidermis-friendly component, and a through hole for mechanically connecting the inside and outside of the body. A biological terminal characterized by having. (3) A biological terminal further characterized by having both the conductive member described in item (1) above and the through hole described in item (2) above.