JPH08266614A - Composite medical material - Google Patents

Abstract

PURPOSE: To provide a composite medical material which is excellent in bioaffinity, biotissue compatibility, and especially in the handling at the time of sawing such as strength, and also excellent in the physical properties such as sewing strength. CONSTITUTION: This composite medical material is that in which sewing treatment has been applied to a membraneous material 2 substantially made up only by a minute layer of the amnion, or using a minute layer not including the epithelium layer, base membraneous layer, and fibroblast layer, by means of the fibers 4 of an invivo decomposable absorptive material.

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 composite medical material used as a wound filling material after surgery, an adhesion preventing material after surgery and the like.

[0002]

2. Description of the Related Art In the case where damage, abnormality, dysfunction, etc. of living tissue occur, it is known that the diseased part is excised and the defective part is supplemented with an artificial material or replaced to cure the disease. It is used more often. The medical materials used in these surgical techniques have biocompatibility, physical properties such as strength and flexibility suitable for the site to be used and the condition, and suitable surgical techniques. Operability is required.

In general, a material derived from a living body is excellent in biocompatibility and histocompatibility, though it may be damaged by an immune reaction caused by transplantation, and has been conventionally used.

[0004] On the other hand, synthetic polymers are also widely used as composite medical materials because they have excellent physical requirements and are easy to adjust, but in terms of biocompatibility and tissue compatibility, they are mentioned above. Many of the materials derived from the living body are inferior, and many proposals have been made to improve them.

The following materials have been conventionally developed as composite medical materials composed of these materials derived from living tissues or synthetic polymers.

[0006] For example, Japanese Patent Publication No. 3-4229 discloses a medical material for supplementation using human amniotic membrane. Further, US Pat. No. 4,361,552 discloses a cover material for burns, which is obtained by cross-linking human amniotic membrane. Further, Japanese Patent Publication No. 58-62662 discloses a structure for a damage cover in which a collagen dispersion gel is attached to a breathable base cloth.

[0007]

However, in the case of filling and repairing a defective part by excision of a diseased part of an abdominal organ, it is impossible to suture the defective part as it is in a soft organ such as the liver. Is. On the other hand, in the case of filling and repairing a defect portion by excision of a bone disease site, a considerable strength is required for suture fixing of the defect portion. In such an example, the element that is required together is a suture reinforcing material having excellent strength and flexibility.

[0008] Therefore, there is a demand for a medical material which solves such a problem and has biodegradability and absorbability. For example, a polyglycolic acid mesh is used to satisfy the above-mentioned problems. However, since it is porous, there is a problem in that body fluid of the applied organ, for example, bile leaks into the gallbladder.

From the above, in the treatment of supplementing a diseased part, the liquid or gas in the affected part does not leak or get lost, has a suitable sutureability, has suture reinforcement, and is decomposed and absorbed in a living body. Promoting regeneration and self-repair of the affected tissue, rich biocompatibility as the same material, rich in operability (easiness of handling such as adhesion to defect in surgical operation, etc.), It is an object of the present invention to collectively solve the problems of maintaining reasonable economic efficiency and satisfying stable supply.

That is, the object of the present invention is to meet the above-mentioned problems of physical compatibility such as biocompatibility, tissue compatibility, strength, flexibility, bodily fluid leakage prevention, workability, etc., and especially handling at the time of suturing. Another object of the present invention is to provide a composite medical material that can satisfy all of the suture strength.

[0011]

According to a first aspect of the present invention, there is provided a composite medical material, wherein a film-like material using only a dense layer that substantially constitutes a biological tissue film is sewn with fibers of a biodegradable and absorbable material. It is a composite medical material that has been treated and reinforced.

Here, the dense layer forming the biological tissue film is a biodegradable and absorbable material consisting of only a dense collagen layer.

The sewing process is a straight stitch on a film material,
Stitching is performed using wave stitches or zigzag stitches.

Further, the fibers of the biodegradable and absorbable material are
It may be a thread-like material such as a thread obtained by cutting and twisting a film-like material using only a dense layer of human amniotic membrane in a narrow width.

In the composite medical material according to the invention of claim 2, in the invention of claim 1, the biological tissue film is human amniotic membrane.

A composite medical material according to a third aspect of the present invention is the composite medical material according to the first or second aspect of the invention, wherein the fibers of the biodegradable and absorbable material are composed mainly of polyglycolic acid, polylactic acid, and a copolymer thereof. And the fiber.

The present invention will be described in detail below. In the present invention, the dense layer that substantially constitutes the biological tissue membrane includes, for example, a dense layer such as human brain dura, human fascia lata, equine pericardium, porcine pericardium, and human amniotic membrane. The amniotic membrane will be described below.

FIG. 5 is a cross-sectional view showing the structure of human amniotic membrane (Nankodo; Basic and Clinical "Placenta" (1981) 31.
Page, Figure 34: Amniotic membrane at 13 weeks gestation).

Referring to FIG. 5, human amniotic membrane comprises an epithelial layer and a basement membrane layer 1, a compact layer 2 having a width of about 10 μm, and a fibroblast layer 3.

The membranous material substantially using only the dense layer of human amniotic membrane in the present invention means only the dense layer 2 obtained by removing the epithelial layer and the basement membrane layer 1 and the fibroblast layer 3 from human amniotic membrane. As described below, the human amniotic membrane is subjected to a predetermined treatment so that the layers other than the dense layer 2 are substantially eliminated. Therefore, it is distinctly different from using the whole amniotic membrane of the prior art.

That is, the membranous material using only the dense layer (dense collagen layer) that substantially constitutes the biological tissue membrane in the present invention is the same as the conventional amniotic membrane using cells and cell membranes. This is a clear difference not only in terms of constitution from the point of substantially not containing it, but also in terms of not causing an immune reaction.

The above-mentioned membranous substance using substantially only the dense layer of human amniotic membrane is excellent in terms of physical requirements such as biocompatibility, tissue compatibility, strength and flexibility. In terms of strength, it may be slightly insufficient especially when suturing with internal organs. Therefore, it is conceivable to reinforce with another reinforcing material to increase the suture strength, but the thickness of the reinforcing material is added and the delicate flexibility is inferior, and there is a difficulty in handling, especially during sewing. Therefore, the inventors of the present invention have made biodegradability and absorption of a membranous substance using only a dense layer that substantially constitutes a biological tissue membrane, for example, a membranous substance using only a dense layer of human amniotic membrane, in vivo. The material is sewn and reinforced to improve its physical requirements such as biocompatibility, tissue compatibility, strength, and flexibility. It is particularly easy to handle during suturing and has suture strength. It has also been found that an excellent composite medical material can be obtained.

Next, a method for producing a medical material in which a film-like material using only a dense layer which substantially constitutes a biological tissue film is sewn with fibers of a biodegradable and absorbable material and reinforced The amnion will be described below as an example.

An epithelial layer and a basement membrane layer 1, a compact layer 2 and
A material using only the dense layer of human amniotic membrane, which is composed of only the dense layer 2 obtained by removing the layers other than the dense layer 2 from the human amniotic membrane formed from the fibroblast layer 3, is prepared, for example, by the following method. Obtainable.

First, only a fetal membrane is excised and separated from a fresh placenta, umbilical cord, fetal membrane, etc. immediately after delivery of an uninfected mother.
The separated fetal membrane is immediately exsanguinated and exsanguinated using physiological saline according to the Japanese Pharmacopoeia.

Next, the blood-removed and blood-removed fetal membrane is desalted and washed with sterile, non-pyrogenic purified water. After desalting and washing, the fetal membrane is allowed to stand in a 0.1% benzalkonium chloride solution of the Japanese Pharmacopoeia solution for 24 hours or more and allowed to stand. Here, the aforementioned benzalkonium chloride submerged treatment is carried out by separating and separating membrane layers such as amniotic membrane, chorion, encapsulating decidua, and floor decidua that compose the fetal membrane, disinfection and sterilization, and cell layer. It is thought to be what causes the transformation of.

The amniotic membrane separated by such treatment is
Ultrasonic cleaning is performed using sterile, non-pyrogenic purified water.

The amniotic membrane thus obtained had a content of 0.01
% Ficin, pH 7.4, 0.2M% phosphoric acid buffer adjustment solution, and allowed to stand at room temperature for 24 hours. Subsequently, the amniotic membrane after the ficin treatment described above is ultrasonically washed with sterile, non-pyrogenic purified water.

In this way, the film material obtained by the above-mentioned processing in which only the essential points are described becomes a film material in which only the dense layer is left out of the various layers constituting the amniotic membrane. In addition, the material using only the dense layer of human amniotic membrane in the present invention in which layers other than the dense layer are removed from the epithelial layer forming the human amniotic membrane, the basement membrane layer, the compact layer, the fibroblast layer, etc. Although it can be obtained by the above-mentioned method, the present invention is not limited to this, and the idea of the present invention is to separate and purify a layer consisting of only a dense layer and use it as a medical material.

The film material obtained by the above-mentioned treatment has the following characteristics. There is no cell layer by microscopic observation. Moreover, an asymmetric matrix structure, which can be presumed to be possessed by the dense layer constituting human amnion, can be observed.

The ratio of the thickness occupied by the dense layer in human amniotic membrane was 70 to 80%, and the measured value obtained by repeating the membrane material obtained by the above treatment 30 times was 77% on average.

Cell-free collagen, 1
It is composed of type 3, type 3, type 4, type 5 and type 16 collagen (J. Biochem. 112, 856-
863 (1992)). From these facts, it can be said that the membrane material obtained by the above-mentioned treatment is a membrane material consisting essentially of the dense layer of human amniotic membrane.

The thus-obtained material consisting essentially of the dense layer of human amniotic membrane is already a film-like strong material and can be used as a medical material without any treatment such as sterilization. In the present invention, since the composite medical material has both handleability and suture strength at the time of suturing as described above, the biodegradable and absorbable material is sewn to be reinforced.

Specific examples of these stitches include wave stitches, straight stitches, and zigzag stitches.
It is not limited to these. Further, the portion of the film-like material that is sewn is not limited, and only the peripheral portion of the film-like material is sewn, all the parts of the film-like material are sewn vertically and horizontally, And so on.

In comparison with the present invention, as shown in FIG. 6, when reinforcing material 7 such as mesh or cloth is vertically sandwiched by membranes 12 made of a medical material, the reinforcing material 7 and the membrane material are used. It takes a great deal of labor to make a close joint with No. 12, and even if the joint is successful, the material after reinforcement will have an unnecessary thickness.

The fibers of the biodegradable and absorbable material are not particularly limited, but preferably include fibers containing polyglycolic acid, polylactic acid, and their copolymers as main components. As a matter of course, a twisted yarn obtained by twisting a film obtained by cutting a film consisting of only a dense layer of human amniotic membrane into a narrow tape shape, and a fibrous material obtained by plying the twisted yarn , Can be used as a reinforcing fibrous material.

In the present invention, the term "consisting essentially of the dense layer of human amniotic membrane" means the epithelial layer forming human amniotic membrane,
It consists of a dense layer obtained by removing layers other than the dense layer from the basement membrane layer, the compact layer, the fibroblast layer, etc., but does not include the epithelial layer, the basement membrane layer, the fibroblast layer at all, or Any substance that is contained only in a trace amount is sufficient, and the meaning is substantially.

The above-mentioned material consisting essentially of the dense layer of human amniotic membrane may be a material obtained by subjecting the material to crosslinking, sterilization, sterilization, or modification treatment.

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

Examples of the cross-linking and modifying treatment include reaction and cross-linking with glutaraldehyde, carbodiimide, succinic anhydride and the like.

[0041]

The composite medical material of the present invention does not become unnecessarily thick in thickness as compared with the conventional one reinforced with a mesh or cloth, and has an appropriate flexibility (that of the material before reinforcement). It is excellent in that it retains (close to flexibility). Therefore, it becomes a medical material that is excellent in the filling of a defective portion and the handleability of a prosthesis.

[0042]

The present invention will be described below with reference to examples.
The present invention is not limited to this.

(1) Working environment A. Work environment Work place All processes except ultrasonic treatment are carried out on a clean bench installed in a clean room (class 100 level).

Worker's clothes The worker wears a sterilized hat, mask, dust-free garment and shoes in the antechamber and enters the clean room.

All the work is carried out by wearing disposable sterile rubber gloves, and new rubber gloves are always replaced when entering or leaving the room or when an unsterilized object is touched.

B. Water used for production Use all water used for production that is treated by the following method.

The raw material water is filtered using a pre-filter and a UF membrane, and the filtrate is periodically collected to detect endotoxin by the Limulus reaction, and used for production only when endotoxin is not detected.

When the device is not used for a long time, 75
Take precautions such as sufficiently replacing with% ethanol to prevent bacterial growth in the device.

The containers and equipment used in each process are 7
It is sufficiently sterilized with 5% ethanol and stored in 0.1% benzalkonium chloride solution before use.

(2) Manufacturing method of human fetal membrane using amniotic membrane The main steps of the manufacturing method will be described below.

The intermediate obtained in each step was 0.1
% Benzalkonium chloride solution.

Separation of Amniotic Membrane from Fetal Membrane A stainless steel container was filled with a 0.1% benzalkonium chloride solution, human fetal membranous membrane was placed, and the amniotic membrane was peeled off by bathing with a gloved hand. The amniotic membrane is thoroughly washed with water to obtain a first intermediate.

Foreign Material Removal (First Time) The first intermediate is spread on a plastic plate to remove the milky white casein-like substance, and thoroughly washed with water to obtain a second intermediate.

Ficin-treated sodium dihydrogen phosphate and disodium hydrogen phosphate were used to adjust the pH of a 0.2 mol phosphate buffer solution to 7 so that sodium chloride was adjusted to 0.9 (v / w)%. And used as a buffer solution. 5 liters (1) of buffer solution is put into a stainless steel container, covered with a lid, and sterilized at 120 ° C. for 30 minutes, and after cooling, 2.5 g of sodium azide is added and dissolved. Ficin (0.5 g) was dissolved in the obtained liquid, 10 second intermediates were placed in the container, allowed to stand at room temperature for 24 hours, and thoroughly washed with water to obtain a third intermediate.

It should be noted that this step is preferably carried out within 24 hours after the completion of the step, more preferably within several hours, and further preferably within 1 hour.

Removal of Foreign Substances (Second Time) The third intermediate is spread on a plastic plate, and while rubbing the surface with a plastic piece, the milky white casein-like substance is removed and sufficiently washed with water to obtain a fourth intermediate.

It is preferable that this step be carried out within 24 hours after completion of the step, more preferably within several hours, and further preferably within 1 hour.

Attaching the frame A square made of polypropylene (width 24
cm, length 33 cm), spread the 4th intermediate on top of this frame, lay a polypropylene square frame on it, and clip it with both frames The body is fixed to form a fifth intermediate body.

Ultrasonic treatment The fifth intermediate is suspended in a stainless steel bath and ultrasonically cleaned for 15 minutes while overflowing water using an ultrasonic oscillator to obtain a sixth intermediate.

Packaging The sixth intermediate is moistened, impregnated with a 0.1% benzalkonium chloride solution, placed in a sterile polyethylene bag and heat sealed.

The film material obtained as described above substantially consists of a dense layer. (3) Quality of Obtained Dense Layer Film The film material obtained as described above and substantially consisting of a dense layer has the following quality.

A transparent or translucent film. The film viewed with a magnifying glass of 10 times or more has no foreign matter remaining on the film other than the smooth dense layer.

The membrane was collected in an Erlenmeyer flask, 100 cc of physiological saline was added thereto, and the mixture was heated at 70 ° C. for 24 hours with an aluminum cap and cooled. It was tested by the substance test method, and it was adapted.

The membrane material is aseptically taken out from the packaging, and a part thereof is cut into small pieces with sterile scissors in an aseptic environment.
5 g was put into a test tube containing 140 cc of thioglycolic acid medium for sterility test, and a bacterium test was carried out by the sterility test method of the Japanese Pharmacopoeia.

Further, the same treatment as in the above-mentioned bacterial test was carried out, and about 1 g thereof was put into a 200 cc flask containing 40 cc of glucose peptone medium for sterility test, and the bacterium test was carried out by the Japanese sterility test method. It fits this.

(4) Application of the obtained dense layer film Example 1 FIG. 1 is a plan view showing an example of the composite medical material according to the present invention.

2 is a partially enlarged plan view of the "a" portion shown in FIG. 1, and FIG. 3 is a partially enlarged plan view of the "b" portion shown in FIG. Further, FIG. 4 shows IV-IV of FIG.
It is sectional drawing shown with a line.

Referring to FIG. 1, this composite medical material has two
A film-like material 2 having a rectangular shape of 2 cm × 31 cm, which is substantially composed of only a dense layer, is reinforced by subjecting it to a sewing thread 4 by a straight stitch.

With reference to FIGS. 1, 2 and 4, the portions indicated by “a” from the outer periphery of each of the four sides of the film-shaped material 2 to the inner side of 2 mm to the inner side of 20 mm are straight lines with an interval of 4 mm and a pitch of 2 mm. It has been sewn by sewing.

Further, referring to FIG. 1 and FIG. 3, the portion indicated by "b" within 20 mm from the outer circumference of each of the four sides of the film-like material 2 is sewn by linear stitching at an interval of 10 mm and a pitch of 6 mm. The treatment is applied vertically and horizontally.

A method of manufacturing the composite medical material shown in FIG. 1 having the above structure will be described below.

First, the film-like material 2 consisting essentially of the dense layer was sterilized and sewn as shown in FIG.
As the sewing thread 4, a thread of polyglycolic acid having a thickness corresponding to the 40th count was used.

The sewn dense layer film thus obtained was dipped in a 2% solution of purified Japanese gelatin,
Rolled with a stainless roller on a stainless steel plate,
The irregularities of the seams were reduced, washed thoroughly with water, fixed to a polypropylene frame with clips, and aseptically dried at 105 ° C.
The thickness of the obtained film material was 16 μm.

On the other hand, in the same process as the above process,
As shown in FIG. 6, a three-layer laminated material in which a mesh 7 of polyglycolic acid having a pore size of 300 μm was sandwiched between two dense layer films 12 had a thickness of 28 μm.

Example 2 A composite medical material having a thickness of 15 μm was obtained by performing the same processing except that the stitching was changed to the zigzag stitch instead of the straight stitch.

[Brief description of drawings]

FIG. 1 is a plan view showing an example of a composite medical material according to the present invention.

2 is a partially enlarged plan view of a portion "a" shown in FIG. 1. FIG.

FIG. 3 is a partially enlarged plan view of a “b” portion shown in FIG. 1.

FIG. 4 is a sectional view taken along line IV-IV in FIG.

FIG. 5 is a cross-sectional view showing the structure of human amniotic membrane.

FIG. 6 is a cross-sectional view showing a structure of an example of a composite medical material including a three-layer laminated material using a reinforcing mesh for comparison.

[Explanation of symbols]

 1 Epithelial layer and basement membrane layer 2 Dense layer 3 Fibroblast layer 4 Suture thread 7 Reinforcing mesh

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Kazuo Kondo 1-2430-47 Hanazono, Tokorozawa, Saitama Prefecture

Claims (3)

[Claims] 1. A composite medical material in which a membranous material using only a dense layer that substantially constitutes a biological tissue film is sewn with a fiber of a biodegradable and absorbable material for reinforcement. 2. The composite medical material according to claim 1, wherein the biological tissue film is human amniotic membrane. 3. The composite medical material according to claim 1, wherein the fiber of the biodegradable and absorbable material is a fiber containing polyglycolic acid, polylactic acid, and a copolymer thereof as a main component. .