JP2905718B2 - Medical material and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical material, and more particularly, to a medical material such as a pledget, a bolster, a patch graft, a medical prosthetic material, and a prosthetic material.

[0002]

2. Description of the Related Art When a living tissue is damaged, abnormal or dysfunctional, an artificial product is used as a medical material to replace or replace the site, and has been widely used in the field of surgical medicine. . In the medical materials used for these, biocompatible, blood and body fluids and human body tissue is biocompatible, in addition to the technique used,
With physical requirements such as tensile strength, tear strength, toughness, and flexibility suitable for the surgical technique, and suitable surgical operability (e.g., easy use by doctors such as adhesion to the affected area, ease of handling, etc.) Is necessary.

In general, materials derived from living organisms are
Although there may be a case where a disorder or the like occurs due to an immune reaction, it is excellent in safety such as biocompatibility and biocompatibility, and has been conventionally used. For example, there are medical materials derived from human brain dura mater, human thigh fascia, equine pericardium, porcine pericardium, and the like.

On the other hand, synthetic polymer medical materials are also widely used as medical materials because of their excellent physical requirements and easy adjustment of the requirements. Many materials are inferior to those derived from, and many proposals have been made for improvement. However, these synthetic polymer medical materials are excellent in physical requirements, and even if biocompatibility and biocompatibility are improved, in terms of bioabsorption and biodegradation, they are materials derived from living tissues. It is inferior to compare.

[0005] The following materials have been conventionally developed as medical materials comprising these biological tissue-derived materials or synthetic polymers.

For example, Japanese Patent Publication No. 3-4229 discloses a supplementary medical material using human amniotic membrane. Further, US Pat. No. 4,361,552 discloses a cover material for a burn in which a human amniotic membrane is crosslinked. Further, Japanese Patent Publication No. 58-52662 discloses a structure for a damaged cover in which a dispersed gel of collagen is adhered to a breathable base cloth.

[0007]

However, in the above-mentioned prior art, the physical requirements such as biocompatibility, strength, flexibility, and operability are individually satisfied, or Although all requirements and properties are moderately satisfied, but the essential properties of each are insufficient, etc., physical requirements such as biocompatibility, strength, flexibility, surgical operability, etc. are summarized. No satisfactory medical material has been found.

[0008] Specifically, for example, a biological tissue membrane such as an amniotic membrane or an amniotic membrane having a cell tissue layer is liable to cause biological rejection, biological activity by cells, fear of contamination with viruses and other pathogens, and incompatibility with biocompatibility. However, it cannot provide complete safety as a medical product.

[0009] As a medical product obtained by completely modifying a biological tissue membrane having a cell tissue layer with glutaraldehyde, a wound repair material derived from horse and pig pericardium has been used in many countries around the world for many years. However, such a chemically modified product shows only the same usefulness as a plastic film material such as polytetrafluoroethylene, that is, safety and efficacy. In addition, this chemically modified product has a defect that, like the plastic film material, it remains permanently in the living body, forms a capsule, and the capsule becomes thickened and enlarged over time. That is, such a chemically modified product has drawbacks in terms of biodegradability and absorbability and ability to regenerate and replace living tissue.

[0010] On the other hand, wound repair materials for human cerebral dura have been used for decades and are recognized as homogenous / replacement wound repair materials. However, since this is a membrane material having a cell tissue, it is not allowed to be applied to a biological region other than the dura mater. In addition, the occurrence of severe side effects, which have recently been judged as Creutzfeldt-Jakob disease after the onset of epilepsy, has been reported after replacement of the dura. Furthermore, since raw materials are collected from humans, the supply capacity is poor,
There is a disadvantage that it is extremely expensive. In other words, this cerebral dura wound repair material has a fatal defect that the provision of medical welfare is unfair.

The object of the present invention is to solve the above-mentioned problems, namely,
It is an object of the present invention to provide a medical material and a method for producing the same, which can satisfy all physical requirements such as biocompatibility, biodegradability and absorbability, strength, flexibility, and operability.

[0012]

That is, the problem to be solved by the present invention is to supply medical materials that exhibit the effects listed below in a lump, and to the medical welfare and medical economy brought by them. In contribution.

(1) The regeneration and self-repair of the defective diseased tissue are effectively completed, and the used medical material is decomposed and absorbed by the human body.

(2) Excellent operability (strength, handling, etc.) in surgical operations. (3) Enable early cure and early discharge.

That is, the medical material according to the first aspect of the present invention is a medical material characterized in that only a dense layer constituting a living tissue membrane is substantially used. It is a decomposable material.

A medical material according to a second aspect of the present invention is characterized in that the dense layer substantially constituting the biological tissue membrane is reinforced with a biodegradable and absorbable material.

According to a third aspect of the present invention, in the medical material according to the first or second aspect, the biological tissue membrane is human amniotic membrane.

A medical material according to a fourth aspect of the present invention is the medical material according to any one of the first to third aspects, wherein the shape is a film.

According to a fifth aspect of the present invention, in the medical material according to the first or second aspect, the dense layer is a film having an asymmetric shape on both sides.

The medical material according to claim 6 is the medical material according to claim 2, wherein the biodegradable and absorbable material has an average pore size of 1
It is a mesh-like material of 00 to 2000 μm.

The medical material according to the invention of claim 7 is the invention of claim 6, wherein the biodegradable and absorbable material is mainly composed of polyglycolic acid, polylactic acid and a copolymer thereof.

The medical material according to the eighth aspect of the present invention is the medical material according to the second aspect of the present invention, wherein the intermediate reinforcing material of the biodegradable and absorbable material is vertically sandwiched by a film using substantially only a dense layer.

According to a ninth aspect of the present invention, there is provided a method of manufacturing a medical material, comprising: laminating a dense layer substantially constituting a biological tissue membrane and a biodegradable and absorbable material; It is characterized in that a succinyl treatment is performed after the gap is fixed by adhesion.

Further, the present invention will be described in detail. In the present invention, a medical material characterized by using only a dense layer substantially constituting a biological tissue membrane is a biological tissue membrane, for example, a human brain dura, a human thigh fascia, an equine pericardium, a pig heart. film,
There are human amniotic membranes and the like, and the human amniotic membrane will be described below. FIG. 1 is a cross-sectional view showing the structure of human amniotic membrane (Nankodo; “Placenta” Basic and Clinical (1981), page 31,
Figure 34: Amniotic membrane at 13 weeks gestation).

Referring to FIG. 1, the human amniotic membrane has an epithelial layer 1A.
And a basement membrane layer 1B, a dense layer 2 having a thickness of about 10 μm,
And a fibroblast layer 3. The medical material according to the present invention comprises, from human amniotic membrane, epithelial layer 1A and basement membrane layer 1
B and the fibroblast layer 3 have been completely removed, and it is completely acytoplasmic, and consists essentially of the dense layer 2 from which the basement membrane layer has been almost completely removed. Therefore, the dense layer membrane derived from human amniotic membrane is distinctly different from the one using the whole amniotic membrane of the prior art.

As an example of the membrane material constituting the present invention, a membrane material consisting essentially of a dense layer of human amniotic membrane has the following characteristics.

[0027] Microscopic observation shows no cytoplasm. In addition, an asymmetric matrix structure presumed to be possessed by the dense layer constituting the human amniotic membrane can be observed.

One of its major components is collagen, which is type I, type III, type IV, type V, and XV
It is composed of type I collagen (J. Bioche
m. 112, 856-863 (1992)).

The membrane material of the present invention consisting essentially of a dense layer of human amniotic membrane comprises a conventional membrane material using the whole human amniotic membrane,
They are completely different in the point that they do not substantially contain cells and in the components, and they are also completely different in their functions, for example, they do not cause an immune reaction due to the absence of cells.

As an example of use in the form of a membrane, there is an anastomosis / supplementation technique in which a surgical site (organ / tissue) is sutured. Then, the strength at the time of suturing is often insufficient.
Therefore, it is necessary to reinforce with a reinforcing material, and reinforce the film with a mesh. The reinforcing material must be a biodegradable and absorbable material, and is not particularly limited as a biodegradable and absorbable material, but is preferably polyglycolic acid, polylactic acid, or a copolymer thereof. Coalescence.

The form of the reinforcing material is not particularly limited, but preferably has an average pore diameter of 10
There is a mesh-like material of 0-2000 μm.

Examples of the sterilization and sterilization treatment include heating (autoclave pressurized heating water treatment and the like), ultraviolet irradiation, electron beam irradiation, gamma ray irradiation, and ethylene oxide gas treatment.

[0033]

In the medical material according to the present invention, only the dense layer substantially constituting the biological tissue membrane is used.

According to the theory, living tissue is formed by cell proliferation using a dense layer as a substrate. Therefore, the use of the dense layer of the living tissue of the present invention enables regeneration, growth and repair of the defective tissue.

In the present invention, only a dense layer obtained by dissolving and removing a cytoplasm layer such as an epithelial layer and a fibroblast layer constituting a living tissue is used. Therefore, side effects caused by cells and cytoplasm are completely eliminated.

[0036]

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

(1) The quality of the dense layer film of the present invention is shown below. It is a transparent or translucent film.

When observed with a magnifier of 10 times or more,
No foreign matter other than the dense layer remains.

A sterile, non-pyrogenic membrane containing a benzalkonium chloride solution.

The membrane was collected in an Erlenmeyer flask, 100 cc of a physiological saline solution was added, and an aluminum cap was added.
The mixture was heated for 4 hours, cooled, the film was removed, and the remaining liquid was used as a test liquid.

The membrane material is aseptically removed from the packaging, and a part thereof is cut into small pieces with sterile scissors under a sterile environment.
5 g was put into a test tube containing 140 cc of a thioglycolic acid medium for sterility test, and a bacterial test was conducted by the sterility test method of the Japanese Pharmacopoeia.

Further, the same treatment as in the above-mentioned sterility test was carried out, and about 1 g thereof was charged into a 200 cc Erlenmeyer flask containing 40 cc of a glucose peptone medium for sterility test, and a fungus test was conducted according to the sterility test method of the Japan Pharmacopoeia. Adapted to this.

(2) Application of Obtained Dense Layer Membrane Weigh 20 g of purified gelatin in Japan and add 500 g of hot water.
cc and water was added to obtain a 2% gelatin solution. A dense layer film material (horizontal 2) made of a polyglycolic acid mesh having a pore diameter of 300 μm was immersed in the above-mentioned liquid, pulled up, and spread on a work table.
2 cm, 31 cm in height), another layer of dense layered membrane material is further layered on a polyglycolic acid mesh with a pore diameter of 500 μm, and the three members are pressed tightly with a glass roller. Gelatin penetrated the dense layer membrane material and was fixed to a polypropylene frame.

The three-layered material fixed to the polypropylene frame was suspended in a sterile vacuum / drying / heating apparatus, and sterile dry air at 105 ° C. was jet-circulated for 24 hours. The obtained laminated material did not peel off even in water. This laminated material was treated with a succinyl reaction solution (0.02 mol at pH 9.0).
The mixture was immersed in 500 cc of a borate buffer and 100 cc of a 5% acetone solution of succinic anhydride at room temperature for 2 hours to carry out a succinyl reaction. After completion of the reaction, the product was sufficiently washed with water, dried, packaged, and sterilized by gamma irradiation at a dose of 2.5 Mrad to obtain a laminated material reinforced medical material.

FIG. 2 is a sectional view showing the structure of an example of the medical material according to the present invention thus obtained.

Referring to FIG. 2, this medical material comprises a reinforcing mesh 7 with a dense layer film material 2 vertically sandwiched therebetween.

The obtained medical material is used as an allograft / replacement wound repair material having anastomosis reinforcing properties, for resection of liver, pancreas, spleen, gallbladder, etc., covering, repairing, prosthetic and incision sites and bronchial suture sites. The suture had a clear effect.

Using any of urea, creatine hydrochloride, etc. as a buffer, 0.15% by weight of collagen
An aqueous solution was prepared at a concentration of, and a laminated material-reinforced medical material was obtained in the same manner as described above, except that the aqueous solution was replaced with the above-mentioned aqueous solution of purified gelatin in Japan.

The obtained material exhibited the same effect as the material obtained in the above.

[0050]

As described above, according to the present invention, the medical material of the laminated material consisting of the dense layer and the biodegradable polymer mesh material substantially constituting the biological tissue membrane can be used to regenerate the tissue affected by the defect. It allows repair and the time until self-tissue regeneration remains, after which it is not decomposed and absorbed or excreted and remains in the human body. Therefore, compared to conventional materials using synthetic polymers and materials using living tissue membranes that include layers other than the dense layer, the technical operability (strength, handleability, etc.) in surgical operations is excellent, and early healing, Early discharge can be possible. Furthermore, it is very excellent in terms of biocompatibility, biocompatibility, and the like.

[Brief description of the drawings]

FIG. 1 is a cross-sectional view showing the structure of a human amniotic membrane.

FIG. 2 is a cross-sectional view showing a configuration of an example of a medical material according to the present invention.

[Explanation of symbols]

 Reference Signs List 1A epithelial layer 1B basement membrane layer 2 dense layer 3 fibroblast layer 7 mesh for reinforcement

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-63-260549 (JP, A) JP-A-5-56987 (JP, A) JP-A-7-116242 (JP, A) (58) Field (Int.Cl. ⁶ , DB name) A61L 27/00

Claims (9)

(57) [Claims] 1. A medical material comprising substantially only a dense layer constituting a biological tissue membrane. 2. A dense layer substantially constituting a living tissue membrane is reinforced with a biodegradable and absorbable material.
Medical materials. 3. The medical material according to claim 1, wherein the biological tissue membrane is a human amniotic membrane. 4. The medical material according to claim 1, wherein the medical material has a film shape. 5. The medical material according to claim 1, wherein the dense layer is a film having an asymmetric shape. 6. The biodegradable and absorbable material has an average pore size of 1.
3. A mesh-like material having a size of from 00 to 2000 [mu] m.
The described medical material. 7. The medical material according to claim 6, wherein the biodegradable and absorbable material is mainly composed of polyglycolic acid, polylactic acid, and a copolymer thereof. 8. The medical material according to claim 2, wherein the intermediate reinforcing material of the biodegradable and absorbable material is vertically sandwiched by a film using only the dense layer. 9. A dense layer substantially constituting a living tissue membrane and a biodegradable and absorbable material are laminated, and the laminate is impregnated with gelatin or collagen, heated and crosslinked, and adhesively fixed between the layers, and then subjected to succinyl treatment. A method for producing a medical material, comprising: