JP2001327520A - In vivo decomposition absorptive tacky adhesive tape for medical purpose - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an in-vivo decomposition absorptive tacky adhesive tape for medical purposes which allows the easy reduction and fixation of a bone fracture segment and formation, fixation, etc., of other tissues when used in an organism in operation and does not require the removal from the inside of the organism by reoperation after the treatment. SOLUTION: The in-vivo decomposition absorptive tacky adhesive tape for medical purposes is constituted by forming a tacky adhesive layer consisting of a themosensitive in-vivo decomposition absorptive tacky adhesive material which exhibits or increases tacky adhesiveness at a temperature above the temperature (about 30 to 40 deg.C) approximate to the body temperature on at least one surface of a tape base material consisting of an in-vivo decomposition absorptive polymer or forming a tacky adhesive layer consisting of a waster sensitive in-vivo decomposition absorptive tacky adhesive material which exhibits or increases the tacky adhesiveness by contact with moisture thereon.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biodegradable and absorbable adhesive tape for medical use embedded in a living body.

[0002]

2. Description of the Related Art Conventionally, a metal osteosynthesis plate, a pin, a screw, and the like have been frequently used for reducing and fixing a complicated fracture. However, these may be harmful to the living body due to elution of metal ions, or may be too strong in strength to weaken the surrounding bones, so that the fractures must be removed from the body after healing. There was a problem that surgery had to be performed.

[0003] Accordingly, the present applicant has developed an osteosynthesis plate, a pin, a screw, and the like made of polylactic acid or the like, which is biodegradable and absorbable. These were excellent in that they had the same initial strength as the living bone, and after the fracture had healed, they were hydrolyzed and absorbed in the living body, so that it was not necessary to perform reoperation.

[0004] However, these biodegradable and resorbable osteosynthesis plates, pins, screws, and the like need to be drilled and screwed into a living bone, as in the case of conventional metal plates. However, there is a problem that it takes time to reduce and fix the fractured part. In particular,
Even if the repaired part is a part where little external force is applied and it is considered that it is enough to simply fix it by taping etc., drilling of living bone with a drill, driving of a pin, screwing of a screw, etc. It was necessary, and the trouble was great.

[0005] In the above case, if there is a decomposable and absorbable adhesive tape which can be used in a living body, it is possible to easily reduce and fix a fracture portion to which a large external force does not act by taping. Adhesive tape has not been developed yet.

With such an adhesive tape, hard tissue and soft tissue other than bone can be easily fixed by taping and the shape thereof can be easily adjusted in surgery in a living body. The efficiency of the operation is greatly improved as compared with the case of fixing with a clip, and furthermore, such an adhesive tape covers the gap between the cut skulls in the operation of angina, etc., and promotes the fusion of the bones. In such cases, effective use is expected.

[0007]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and is used in a living body during surgery to easily perform reduction and fixation of a fractured portion and formation and fixation of other tissues. It is an object of the present invention to provide a biodegradable and absorbable adhesive tape for medical use that does not need to be removed from the living body after remedy after healing.

[0008]

Means for Solving the Problems The bioabsorbable adhesive tape for medical use according to the present invention, which solves the above-mentioned problems, has a temperature close to body temperature (approximately) on at least one surface of a tape base made of a biodegradable absorbent polymer. 30 ° C to 40 ° C) or more, a pressure-sensitive adhesive layer made of a heat-sensitive biodegradable and absorbable pressure-sensitive adhesive material that develops or increases tackiness at a temperature of 30 ° C or higher, or a water-sensitive layer that develops or increases tackiness in contact with moisture. Characterized in that an adhesive layer comprising an in vivo biodegradable and absorbable adhesive is formed.

[0009] Such an adhesive tape can develop or increase its adhesiveness by heating it to a temperature higher than the temperature close to the body temperature or bringing it into contact with water during surgery, and it can be used for fractures. It is embedded in a living body while performing reduction and fixing with other tissues. This adhesive tape maintains the adhesiveness and maintains the fixing force until the fractured portion or the like is healed. Then, after healing, both the tape base material and the adhesive layer of the adhesive tape are hydrolyzed by contact with the body fluid, and are eventually completely absorbed by the living body. Therefore, there is no need to remove the adhesive tape from the living body by performing a reoperation after healing.

As the base material of the pressure-sensitive adhesive tape of the present invention, a nonwoven fabric, a woven fabric, a film and the like of a biodegradable and absorbable polymer are suitable, and those having a thickness of 20 to 500 μm are preferably used. When the tape base material is thinner than 20 μm, the strength of the pressure-sensitive adhesive tape, particularly, the tear strength may be reduced, and the tape may be easily cut. When the tape base material is thicker than 500 μm, the time required for decomposition and absorption in a living body increases. Inconveniences such as reduced flexibility arise. The more preferable thickness of the tape base is 40 to 300 μm, and more preferably 50 to 150 μm.

[0011] The nonwoven fabric serving as the tape base material is formed by entangled and fused with long fibers of a biodegradable and absorbable polymer. For example, a solution of the biodegradable and absorbable polymer is continuously discharged in a fibrous form from a nozzle. Nonwoven fabrics that are entangled and welded while being entangled, and nonwoven fabrics in which biodegradable absorbent polymer long fibers cut to a predetermined length are deposited so as to be entangled with each other and welded by means such as thermocompression bonding are used.
The thickness of the long fiber is 50 μm or less, and the weight per unit area is 1 to 20 g.
/ M ² and a nonwoven fabric having a thickness of about 20 to 300 μm are preferably used.

When the long fibers of the nonwoven fabric are thicker than 50 μm, the apparent rate of hydrolysis in the living body becomes slow, and the period until absorption by the living body becomes long. Further, a nonwoven fabric having a basis weight of less than 1 g / m ² has insufficient tear strength, while a nonwoven fabric having a basis weight of more than 20 g / m ² has poor flexibility and a long period of time required for decomposition and absorption in a living body. The more preferable fiber thickness of the nonwoven fabric is 5 to 15 μm, and the more preferable basis weight is 3 to 10 g / m ² .

The long fibers of the non-woven fabric may be porous fibers or non-porous fibers. However, if the fibers are porous, the surface area of the non-woven fabric which comes into contact with body fluids in the living body increases, so that hydrolysis is promoted. There is an advantage that the time required for absorption is further reduced.
The fibers of the porous biodegradable and absorbable polymer can be easily dissolved by dissolving the polymer in a mixed solvent of a solvent and a non-solvent and discharging the polymer solution into a fibrous form through a nozzle, as described later. Obtainable.

The woven fabric used as the tape base material is plain-woven, twill-woven, or satin-woven with a porous or nonporous biodegradable and absorbable polymer thread (thickness of about 10 to 500 μm). Those are suitable.

On the other hand, the film used as the tape substrate is a biodegradable and absorbable polymer film obtained by an inflation method or another known film forming method, and not only an unstretched film but also a stretched film is used. Is done. Since the stretched film has a high tensile strength, if this is used as a tape substrate, a durable adhesive tape having a high tensile strength can be obtained.

The film may be nonporous or porous. The use of a porous film has an advantage that the apparent hydrolysis proceeds rapidly because the film is rich in flexibility even when the film is thick, and the volume is small. Further, a porous film having open cells is suitable, and in particular, the expansion ratio is 2 to 2.
About 10 times is preferably used. Foaming ratio is 2
A porous sheet smaller than doubled has a slower rate of decomposition and absorption in a living body, and a porous sheet having an expansion ratio larger than 10 times has reduced tear strength and is easily cut.

The biodegradable and absorbable polymers used as raw materials for the above-mentioned nonwoven fabrics, woven fabrics, films and the like include polylactic acid, polyglycolic acid and various polylactic acids which have already been practically used and whose safety in vivo has been confirmed. Polymers and the like are preferably used.

As the polylactic acid, a homopolymer of L-lactic acid or a copolymer of D-lactic acid and L-lactic acid is used. In particular, D-lactic acid and L-lactic acid are used in a molar ratio of 30:70 to 70:30. Copolymerized copolymers are preferably used. Nonwoven fabrics and films made of such copolymers have the advantage that hydrolysis in the living body proceeds promptly and is almost absorbed by the living body in about half a year or more. A more preferred copolymer is a racemic copolymer obtained by copolymerizing D-lactic acid and L-lactic acid in a molar ratio of 50:50.

The polylactic acid copolymer includes lactic acid-
Among glycolic acid copolymers and lactic acid-caprolactone copolymers, those having a relatively high molecular weight having a viscosity to form fibers or films can be used. In particular, the molar ratio of lactic acid to glycolic acid or caprolactone is 99: 1 to 1 Those in the range of 50:50 are preferably used. In addition, a copolymer of polylactic acid and polyethylene glycol, a copolymer of polylactic acid and polypropylene glycol, and the like can also be used as a raw material polymer for the tape base.

The molecular weight of the above-mentioned biodegradable and absorbable polymer may be at least a molecular weight capable of forming a fiber, a film or the like, and is usually a polymer having a viscosity average molecular weight of 50,000 or more. it can. But,
If the upper limit of the molecular weight exceeds 600,000 and becomes too high, it becomes difficult to eject fibers from the nozzle and form a film, and it takes a long time to decompose and absorb in the living body. Average molecular weight of 100,000 to 30
It is preferred to use biodegradable and absorbable polymers in the range of 10,000.

The pressure-sensitive adhesive layer laminated on at least one side of the tape base as described above has a temperature close to the body temperature (about 30 ° C.).
-40 ° C) or more, a heat-sensitive biodegradable and absorbable adhesive that develops or increases tackiness at a temperature of at least or a water-sensitive biodegradable and absorbable material that develops or increases tackiness in contact with moisture. It is a layer made of an adhesive. The thickness of the adhesive layer is preferably about 30 to 300 μm. If the thickness is less than this, the adhesive strength may be insufficient. On the other hand, even if it is thicker, the corresponding improvement in adhesive strength cannot be obtained, but rather, the amount of the substance to be decomposed and absorbed becomes too large, and the time required for decomposition and absorption in the living body becomes longer. Such inconveniences occur.

The above-mentioned heat-sensitive biodegradable and absorbable adhesive is specifically a copolymer of p-dioxanone and another biodegradable and absorbable monomer. 20
It is a plastic adhesive having a weight average molecular weight of 000, and is preferably 5,000 to 60,000.
P-dioxanone having a weight average molecular weight of 000 and D
Copolymer with lactic acid, copolymer of p-dioxanone having a weight average molecular weight of 5,000 to 60,000 and L-lactic acid, p-dioxanone having a weight average molecular weight of 5,000 to 60,000 And a copolymer of D, L-lactic acid and
P having a weight average molecular weight of 8,000 to 50,000
A copolymer of dioxanone and trimethylene carbonate, a copolymer of p-dioxanone having a weight average molecular weight of 10,000 to 100,000 and ε-caprolactone, or a mixture of two or more thereof; It is a biodegradable and absorbable plastic sticky substance made of In particular, a copolymer of p-dioxanone and meso-D, L-lactide having a weight average molecular weight of 5,000 to 60,000 is excellent in tackiness and can be used very suitably. In addition, biodegradability of a star-shaped copolymer having a branched chain of the above copolymer synthesized by mixing polyfunctional alcohols such as glycerin, polyglycerin, pentaerythritol, and star-shaped polyethylene glycol. A plastic adhesive can also be suitably used.

These copolymers are essentially terpolymers since p-dioxanone is a dehydration condensate of glycolic acid and ethylene glycol. The structural formula of the copolymer of p-dioxanone and D-, L- or D, L-lactic acid is as shown in the following [Formula 1], and the structural formula of the copolymer of p-dioxanone and trimethylene carbonate is As shown in the following [Chemical formula 2], the structural formula of the copolymer of p-dioxanone and ε-caprolactone is as shown in the following [Chemical formula 3]. These copolymers may be in either a block or random arrangement. In addition, when the D-form and the L-form are mixed as optical isomer monomers, the copolymer of [Formula 1] can be regarded as a quaternary copolymer.

[0024]

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[0025]

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[0026]

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As described above, p-dioxanone which is a condensate of glycolic acid and ethylene glycol is used as a main component, and D-, L-, D, L-lactic acid, trimethylene carbonate, or ε-caprolactone is copolymerized therewith. The resulting copolymer has a relatively small weight average molecular weight of about 2,000 to 200,000, in which the molecular arrangement is disturbed and the cohesion is not so large. It is a copolymer. A copolymer having a weight average molecular weight of about 6,000 to 100,000 is a relatively hard solid (sometimes rubbery or solid wax-like) having no tackiness in a temperature range lower than 30 ° C.
In a temperature range above the temperature around human body temperature (30 ° C. to 40 ° C.) or more, the material softens and exhibits plasticity, and at the same time, exhibits sufficient adhesiveness to fix or temporarily fix a living tissue or the like by contact. In a higher temperature range, it becomes a kind of hot melt type sticky substance which increases fluidity and changes into a viscous substance such as starch syrup, paste or jelly. The copolymer having a weight average molecular weight of 2,000 to 60,000 exhibits tackiness even at room temperature, and has a weight average molecular weight of 60,000 to 20.000.
Even if heated, the 000 copolymer hardly exhibits sufficient tackiness.

By the way, the adhesives made of these copolymers have an adhesive strength at 37 ° C. of 100 to 15 according to the test method of 90 ° peeling method of JIS Z 0237-1991.
Approximately 00 g (however, the width of the sample is 1/2 inch and the pulling speed is 300 mm / min), and the magnitude of the adhesive force varies depending on the type of monomer copolymerized with p-dioxanone. D, L-lactic acid> racemic-D, L-lactic acid> L-lactic acid, D-lactic acid> trimethylene carbonate> ε
-In order of caprolactone. Then, the sticky substance made of these copolymers softens to an extent having a Shore hardness of 70 or less at 37 ° C.

Above all, an adhesive made of a copolymer of p-dioxanone and D, L-lactic acid, L-lactic acid, or D-lactic acid has an appropriate decomposition and absorption rate, and is in vivo as described later. The substance decomposes remarkably in 2 to 3 weeks when it is fast due to contact with body fluids and in 2 to 3 months when it is late. Then, in a fast case, it is absorbed in a living body in 2-3 months, and in a slow case, it is excreted out of the body and disappears in 6 to 12 months.

The proportion occupied by p-dioxanone in the above copolymer must be 5 to 95 mol%. p
When the proportion of dioxanone exceeds 95 mol%,
The tackiness and other physical properties of the copolymer are substantially the same as those of the homopolymer of p-dioxanone.
If the amount is less than mol%, the physical properties of the copolymer become substantially the same as those of the homopolymers of the other copolymer components, so that it cannot be a sticky substance for the purpose of the present invention. A more preferable ratio of p-dioxanone is 15 to 85 mol%,
The most desirable ratio is 30 to 80 mol%. A copolymer containing p-dioxanone in this range has good tackiness and free plasticity in a temperature range around body temperature (30 ° C. to 40 ° C.), and is practical even at a normal body temperature of 37 ° C. Has shape retention.

The weight average molecular weight of the copolymer is in the range of 2,000 to 200,000 as described above. If it exceeds 200,000, the copolymer lacks flexibility even in a temperature range of 30 ° C. or more. Disadvantages such as reduced adhesiveness and plasticity. In addition, the period required for decomposition and absorption in the living body is also prolonged. On the other hand, when the weight average molecular weight is less than 2,000, the copolymer approaches the liquid, there is excessive stickiness, stringiness is severe, shape retention is lost, and as an adhesive constituting the adhesive layer of the adhesive tape, It becomes difficult to use. The molecular weight of each preferred copolymer is as described above.

Adhesives comprising the above-mentioned copolymers include copolymers of p-dioxanone and D, L-lactic acid, poly-p-dioxanone, having a weight average molecular weight greater than the weight average molecular weight of the copolymer. , Poly-D, L-lactic acid and the like may be further mixed. By mixing a polymer having a high weight average molecular weight in this way, the shape retention of the sticky substance can be improved, and the rate of decomposition in vivo can be slightly reduced.

As the polymer having a high weight average molecular weight to be mixed, a polymer having a weight average molecular weight of not less than the weight average molecular weight of the above-mentioned copolymer and not more than about 200,000 is suitable. Is disadvantageous in that it takes a longer time than necessary for decomposition and absorption. The mixing ratio of the polymer having a high weight average molecular weight is 5 to 3
The content is preferably in the range of 0% by weight. Mixing more than 30% by weight requires long time for decomposition and absorption,
Adhesiveness and plastic deformation are poor, and if less than 5% by weight is mixed, the mixing effect cannot be substantially obtained.

The sticky substance comprising the above-mentioned copolymer is
The porous body may be formed by including innumerable air bubbles. The inclusion of air bubbles in this way makes it easier for body fluids to penetrate into the adhesive through the air bubbles when implanted in a living body, so that the hydrolysis of the adhesive can be accelerated and the surrounding tissue cells and the body fluid can adhere to the adhesive. There is an advantage that the tissue can be reconstructed quickly because it is guided to the inside and grows.

Further, the adhesive layer made of the above-mentioned copolymer adhesive is provided with a water-absorbing polymer such as glycerin or a polymer thereof, polyvinyl alcohol, hyaluronic acid, alginic acid (soda) or a polymer thereof, polyethylene glycol and chitosan. Alternatively, by adding one or more kinds of oxidized cellulose fibers, microfibrous collagen, or the like, water sensitivity may be additionally provided. When such a water-absorbing polymer is contained, the polymer absorbs water when it comes into contact with body fluids or blood in the body, and the above-mentioned copolymer of the adhesive layer causes a decrease in adhesiveness upon contact with water. This has the advantage of having a hemostatic effect.

On the other hand, as the water-sensitive biodegradable and absorbable adhesive which constitutes the adhesive layer, fibrin glue, a gelatin adhesive, a chitosan adhesive, a collagen adhesive or the like can be used with a small amount of a crosslinking agent. The resulting adhesive is used alone or as a mixture. Fibrin glue is a biological adhesive in which fibrinogen, which is a water-soluble plasma protein, is limitedly decomposed into fibrin by the enzymatic action of thrombin, and the degraded fibrin is molecularly associated and gelled. The gelatin-based adhesive is an adhesive obtained by cross-linking bio-derived gelatin and resorcinol with formalin.
The chitosan-based adhesive is an adhesive obtained by treating biologically-derived chitosan with an acid, and the collagen-based adhesive is an adhesive obtained by adding a crosslinking agent to alkali-solubilized collagen and crosslinking the collagen. When the adhesive with a reduced amount of the cross-linking agent of such an adhesive is applied to a fracture portion or the like using an adhesive tape applied to a tape base material as an adhesive, it comes into contact with body fluids or blood. Adhesion can be expressed or increased and fixed.

Among the above-mentioned heat-sensitive or water-sensitive adhesives for biodegradable absorption in the body, the heat-sensitive adhesive does not use formalin, an acid, or a cross-linking agent used in the water-sensitive adhesive. These adverse effects on the living body can be eliminated, and the adhesive strength is also strong, so that they are preferably employed.

The above-mentioned heat-sensitive or water-sensitive biodegradable and absorbable pressure-sensitive adhesive may be used alone to form a pressure-sensitive adhesive layer by laminating on a tape base material. An appropriate amount of a water-sensitive pressure-sensitive adhesive may be added to form a pressure-sensitive adhesive layer having both properties of heat sensitivity and water sensitivity.

The pressure-sensitive adhesive layer of the present invention in which the pressure-sensitive adhesive layer comprising the heat-sensitive or water-sensitive biodegradable and absorbable pressure-sensitive adhesive is formed on at least one surface of the above-described tape base material, The ceramic powder may be contained in the adhesive layer or both the adhesive layer and the tape substrate. When the fractured portion is taped with the adhesive tape containing the bioceramic powder, for example, there is an advantage that the adhesive tape and the bone are strongly bonded and integrated by the osteoconductivity of the bioceramic powder.

Examples of the bioceramics powder include sintered hydroxyapatite, bioglass, ceravital, apatite wollast glass ceramics, wet (unfired or unfired) hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, dicalcium phosphate, Bioactive substances such as calcium phosphate and calcite are used, and the preferable content thereof is 5 to 50% by weight in the case where it is contained in any of the tape substrate and the adhesive layer. When the content is more than 50% by weight, the tape base material and the adhesive layer are weakened, and when the content is less than 5%, almost no improvement in bondability with bone is observed.

Further, an effective amount of various cytokines, chitin or chitosan derivatives, various drugs or hormones may be contained in the adhesive layer or both the adhesive layer and the tape substrate. Examples of cytokines include TG
F-β (transforming growth factor), EGP (epidermal growth factor), FGF (fibroblast growth factor), IFN
_s (various interferons), LAF _s (various interleukins), BHP _s (various bone growth factors) and the like are used. Further, as the main drug, rheumatism therapeutic agent (anti-rheumatic drugs, steroids, immunosuppressants, etc.), osteoporosis agents (calcium preparations, lubricity vitamin D, vitamin K _2, calcitonin, ipriflavone, estrogen , Diphosphonic acid derivatives, parathyroid hormone, new steroid derivatives, bone forming proteins, etc.),
Anticancer agents (adriamycin, cisplatin, mitomycin, 5-fluorouracil and the like), antibacterial agents, constituent substances and the like.

The medical in vivo degradable and absorbable adhesive tape of the present invention described above in detail is heated to a temperature higher than a temperature close to the body temperature or is brought into contact with water during surgery to improve the adhesiveness. Expressing or increasing, or applying and raising the temperature to around the body temperature to develop or increase the adhesiveness, applying the tape by a simple taping work, reducing and fixing the fracture part and fixing other tissues, It is buried in the living body while performing temporary fixing. The adhesive tape buried in this way maintains the adhesiveness by contact with body temperature or body fluid, and maintains the fixing force until the fractured part or the like is healed. After healing, both the tape base and the adhesive layer of the adhesive tape are hydrolyzed by contact with bodily fluids, and are eventually completely absorbed by the living body. There is no need to take out.

As described above, the pressure-sensitive adhesive tape of the present invention can reduce and fix a fractured portion, fix other tissues, and temporarily fix it by a simple taping operation. Therefore, a screw made of another metal or an absorbent polymer can be used. The efficiency of the operation is greatly improved compared to fixed materials such as plates and pins, so that the time required for the operation can be significantly reduced, and the burden of reoperation on the patient can be eliminated. Become.

Next, a specific method for producing the pressure-sensitive adhesive tape of the present invention (the tape base is a non-woven fabric) will be described.

First, the biodegradable and absorbable polymer for a tape substrate described above is dissolved in a solvent capable of dissolving the polymer or a mixed solvent of this solvent and a non-solvent having a boiling point higher than that of the solvent. Prepare solution. The polymer solution prepared by dissolving the biodegradable polymer in the former solvent is used when preparing a non-woven tape base material composed of non-porous long fibers, and the biodegradable polymer is used in the latter mixed solvent. The dissolved polymer solution is used when producing a nonwoven tape base material composed of porous long fibers.

As the above-mentioned solvent, a solvent having a low boiling point which is easily volatilized at a temperature slightly higher than room temperature, for example, methylene chloride,
Chloroform, 1,1-dichloroethane and the like are used, among which low-toxic methylene chloride having the lowest boiling point and the highest vapor pressure is most suitable. In addition, as the non-solvent, a monohydric alcohol having excellent compatibility with the solvent and having a boiling point in the range of 60 to 110 ° C., for example, methanol, ethanol, 1-propanol, 2-propanol, ter-butanol, and ter-pentanol Among them, ethanol, 1-propanol and 2-propanol, which are less toxic and less odor, are preferably used. Further, those obtained by adding a small amount of water to these monohydric alcohols are also used.

The concentration of the polymer solution is suitably adjusted within the range of 0.5 to 10% by weight in consideration of the molecular weight of the biodegradable and absorbable polymer to be dissolved. The higher the concentration of the solution is, the thicker it is. Therefore, it is preferable to control the thickness of the long fiber formed by adjusting the concentration.

When the preparation of the polymer solution is completed, the polymer solution is continuously discharged in a fibrous form from a nozzle and sprayed evenly on the planar support to produce a nonwoven fabric. The spraying amount is 20 to 300 μm in thickness and the basis weight is 1
It is necessary to control so as to obtain a nonwoven fabric of ２０20 g / m ² .

When the polymer solution is discharged and sprayed in a fibrous form as described above, the discharged long fibers are entangled and welded while being folded, and the biodegradable and absorptive polymer solidified due to the diffusion of the solvent. A nonwoven fabric made of long fibers is formed.
In that case, if the polymer solution is a solution of the polymer in a solvent, a non-woven fabric composed of non-porous long fibers is formed. A nonwoven fabric made of long fibers is formed.

When a tape base made of a nonwoven fabric containing bioceramic powder or the like is prepared, a polymer solution in which the powder is uniformly dispersed is discharged from a nozzle or a dispersion of the powder is dispersed. And the polymer solution may be discharged from the two nozzles together, or the dispersion of the powder may be sprayed dropwise onto the polymer solution discharged at the outlet of the nozzle.

When the preparation of the tape base comprising the nonwoven fabric of the biodegradable and absorbable polymer is completed, the above-described heat-sensitive biodegradable and absorbable adhesive is heated to 50 to 60 ° C. A liquid, which is applied to one or both sides of the tape base material by a coating means such as a bar coat to a uniform thickness, and then cooled and solidified at room temperature of 30 ° C. or less to obtain a thickness of 30 to 30.
An adhesive layer having a thickness of 0 μm is formed on one or both sides of the tape substrate. Then, this is cut into a predetermined tape width, wound up in a roll shape, and subjected to a sterilization treatment to obtain an adhesive tape product. In this case, when a releasable film such as a polyethylene film is overlaid and wound into a roll, the storage temperature becomes 30 ° C.
Even when the temperature becomes higher than or equal to ° C., it is preferable because the adhesive tapes can be prevented from sticking to each other.

When forming an adhesive layer containing bioceramics powder or the like, the powder is uniformly mixed and dispersed in a viscous liquid obtained by heating the biodegradable and absorbable adhesive, and the tape base material is mixed. May be applied.

In the case of forming an adhesive layer made of a heat-sensitive biodegradable and absorbable adhesive which also has water sensitivity,
Heat-sensitive biodegradable absorptive adhesive is heated to a viscous liquid, and the above-mentioned water-absorbing polymer or microfibrous collagen is uniformly mixed and dispersed therein, or applied to a tape substrate, or What is necessary is just to apply | coat and dry the solution which melt | dissolved the said heat-sensitive adhesive substance and the water-absorbing polymer in a solvent, and uniformly mixed them to a tape base material.

Further, in order to form an adhesive layer composed of a water-sensitive biodegradable and absorbable adhesive, in the case of an adhesive layer of fibrin glue, a fibrinogen solution is applied to a tape base, and thrombin, abrotinin, A calcium chloride mixed solution may be applied, or a fibrinogen solution and a mixed solution of thrombin, abrotinin and calcium chloride may be mixed and applied to a tape substrate. Also, when a gelatin-based adhesive layer is formed, gelatin and resorcinol are applied to a tape base in advance, and a formalin crosslinking agent is applied, or
Alternatively, gelatin and resorcinol may be mixed with a crosslinking agent, formalin, and applied to the tape substrate. Furthermore, in the case of a chitosan-based adhesive layer, a layer obtained by treating chitosan with hydrochloric acid may be applied to the tape base material.In the case of a collagen-based adhesive layer, a crosslinking agent is added to alkali-solubilized collagen, and the tape base material is added. May be applied.

Next, more specific embodiments of the present invention will be described.

Example 1 The viscosity average molecular weight (Mv) was 2
A racemic copolymer of 10,000 D-lactic acid and L-lactic acid (D / L
= 50/50) was dissolved in dichloromethane to prepare a polymer solution having a concentration of 4%. The polymer solution is continuously discharged in a fibrous form from a spray nozzle (diameter: 1 mm) at a discharge pressure of 735 KN / m ² , and is sprayed onto a planar support, whereby long fibers having a fiber diameter of 1 to 50 μm are entangled and welded. 90 to 110 μm in thickness, weight per unit area 6.5 g /
It was obtained m ² of non-woven fabric.

On the other hand, p-dioxanone (DOX) 10.
2 g (0.1 mol) and 14.4 g (0.1 mol) of D, L-lactide (D, L-LA) were placed in a glass container, and 300 ppm of an initiator (lauryl alcohol) and 100 ppm of a catalyst (2-ethylhexanetin) were added. After being dispersed in toluene and added, the mixture was dried under reduced pressure with a vacuum pump for 20 hours. After removing toluene, the air in the glass container was replaced with N ₂ gas, and the tube was sealed under reduced pressure. The copolymer was advanced in a 170 ° C. oil bath while stirring the interior at regular intervals, and after a predetermined time, the polymerization vessel was taken out to stop the reaction, thereby obtaining a polymer. After dissolving this in acetone, it is purified by precipitating in ethanol to remove unreacted substances and the like, and has a weight average molecular weight of 0.76, 11,000, 1.5
10,000, 25,000, 86,000, and 218,000 copolymers were obtained.

Then, the above nonwoven fabric was used as a tape base material, and a viscous liquid obtained by heating each copolymer at 80 ° C. to a thickness of 100 ± 10 μm was coated on one surface of the nonwoven fabric and cooled at room temperature. The tape was cut to a width of 15 mm to obtain three types of adhesive tapes capable of absorbing and dissolving in vivo.

The properties of these tapes and the adhesion to SUS304 at 37 ° C. were measured in accordance with the 90 ° peel test method of J 試 験 S Z 0237-1991 (provided that the width of the sample was 15 mm and the length was 250 m).
m, and the tensile speed was 300 mm / min).

[0060]

[Table 1]

From these measurement results, it is found that the pressure-sensitive adhesive tape having a weight-average molecular weight of the copolymer of the adhesive layer of 15,000 or 25,000 is excellent in handleability at room temperature, It was found that the pressure-sensitive adhesive layer had good plasticity and had sufficient pressure-sensitive adhesive strength for use in fixing fractured parts to which a large external force does not act or for temporary fixing. However, the pressure-sensitive adhesive tape having a weight average molecular weight of 11,000 of the copolymer of the pressure-sensitive adhesive layer is
Although the interface at the interface between the adhesive layer and the base material has low adhesion and is difficult to handle, it still has sufficient adhesive strength for fixing a fractured portion. In addition, the adhesive tape of a copolymer having a weight average molecular weight of 0.760,000 has a slight fluidity at room temperature, and it is difficult to maintain shape retention, but it has an adhesive force and can fix a fracture portion or the like. I was ready to do it. The pressure-sensitive adhesive tape having a copolymer having a weight average molecular weight of 86,000 had a low adhesive strength, but had adhesive properties when heated, and had a sufficient adhesive strength for fixing a fractured portion. Further, when the weight average molecular weight of the copolymer is 2
The adhesive tape of 18,000 did not exhibit adhesive strength even when heated. From these, the copolymer of p-dioxanone and D, L lactic acid has a weight average molecular weight of 5,000 to
It can be seen that those having a size of about 60,000 are most preferable in terms of handleability and adhesive strength. If the weight average molecular weight is less than 5,000, the adhesive strength is low, but it has sufficient adhesive strength for fixing, but it may be unsuitable due to high fluidity, so a molecular weight of at least 2,000 or more is required. Yes,
Therefore, it is necessary to maintain shape retention. Further, it was found that when the weight average molecular weight was 200,000 or more, no adhesive force was exhibited even by heating, and it was difficult to employ the composition.

Further, the tensile breaking strength of these adhesive tapes was measured (however, the width of the sample was 15 mm, the length was 50 mm,
When the tensile speed was 300 mm / min), it was 6 to 120 KN / m ² irrespective of the weight average molecular weight of the adhesive layer. From this, it was found that the material had sufficient tensile strength to be used for reduction fixation and temporary fixing of a fractured part.

Example 2 A racemic copolymer of D-lactic acid and L-lactic acid (D / L = 50/50) having a viscosity average molecular weight (Mv) of 210,000 was prepared in the same manner as in Example 1. A non-woven fabric was produced. On the other hand, meso-D, L-lactide was used instead of D, L-lactide.
Using lactide, a copolymer of p-dioxanone and meso-D, L-lactide [p-
Dioxanone / meso-D, L-lactide = 1/1 (molar ratio)], each having a weight average molecular weight of 11,000,
15,000 and 25,000 were obtained. Then, a viscous liquid obtained by heating each copolymer to 80 ° C. was applied to one side of the nonwoven fabric to a thickness of 100 ± 10 μm, cooled at room temperature, cut into a tape width of 15 mm, and decomposed in vivo. An absorbent adhesive tape was obtained.

The properties of these tapes and the adhesive strength to SUS304 at 37 ° C. according to the 90 ° peel test method of JΙS Z 0237-1991 were measured (provided that the width of the sample was 15 mm and the length was 250 m).
m, and the tensile speed was 300 mm / min).

[0065]

[Table 2]

From these measurement results, it can be seen that the p-dioxanone / meso-D, L-lactide copolymer has a larger adhesive strength than the p-dioxanone / D, L-lactide copolymer. This is thought to be because the molecules composed of meso-D, L-lactide are due to the effect of the alternating arrangement of D-, L-lactide.

Example 3 In the same manner as in Example 1, a racemic copolymer (D / L = 50/50) of D-lactic acid and L-lactic acid having a viscosity average molecular weight (Mv) of 210,000 was prepared. While producing a nonwoven fabric, the weight average molecular weight is 11,000, 15,000,
A copolymer of 20,000 p-dioxanone (DOX) and D, L-lactide (D, L-LA) was synthesized, and unsintered hydroxyapatite (u-HA) was added to these copolymers.
(Particle size: 2 to 3 μm) was mixed with 50 wt% as an adhesive to obtain a 15 mm-wide biodegradable and absorbable adhesive tape.

The properties of these tapes were as follows:
Then, the adhesive strength to SUS304 was measured at 37 ° C. according to the 90 ° peel test method of JIS Z 0237-1991 (however, the width of the sample was 15 mm and the length was 250 m
Table 3 shows the results obtained when m and the tensile speed were 300 mm / min. In addition, this biodegradable and absorbable adhesive tape was heated at 37 ° C.
Table 4 shows the results of examining the relationship between the immersion time and the decrease in molecular weight.

[0069]

[Table 3]

As a result, it was found that mixing of 50% by weight of u-HA (particle diameter: 2 to 3 μm) can adjust the adhesiveness and impart the shape retention of the adhesive layer.

[0071]

[Table 4]

The results show that a tape base consisting of a nonwoven fabric of a racemic copolymer of D-lactic acid and L-lactic acid (D / L = 50/50), p-dioxanone (DOX) and D, L-lactide (D , L-LA), the biodegradable and absorbable adhesive tape using an adhesive layer made of a copolymer with L-LA) is likely to be hydrolyzed and absorbed in a relatively short time in vivo. Was.

Example 4 Viscosity average molecular weight (Mv) was 2
A racemic copolymer of 10,000 D-lactic acid and L-lactic acid (D / L =
50/50) in a mixed solvent of dichloromethane and ethanol (dichloromethane / ethanol = 10/0, 10/50).
3, 10/6), and three types of nonwoven fabric having a thickness of 90 to 110 μm were prepared in the same manner as in Example 1 and used as substrates. Then, p-dioxanone (DOX) having a weight average molecular weight of 15,000 prepared in Example 3
And a copolymer of D, L-lactide (D, L-LA) with u
As a pressure-sensitive adhesive layer, a mixture of 50% by weight of -HA (particle size: 2 to 3 µm) was used to obtain three types of pressure-sensitive adhesive tapes having a width of 15 mm in vivo.

For these adhesive tapes, JIS Z
The adhesive strength to SUS 304 was measured at 37 ° C. according to the 90 ° peel test method of 0237-1991 (provided that the width of the sample was 15 mm, the length was 250 mm, and the tensile speed was 300 mm / min). In addition, the tensile breaking strength of these adhesive tapes was measured (however, the width of the sample was 15 mm,
The length was 50 mm and the tensile speed was 300 mm / min). Table 5 shows the results.

[0075]

[Table 5]

From these results, the production of a non-woven fabric of a racemic copolymer of D-lactic acid and L-lactic acid (D / L = 50/50)
It was found that the case where a polymer solution containing no ethanol was used had a sufficient tensile strength to be used for fixing or temporarily fixing a fractured portion. However, in order to accelerate the absorption due to hydrolysis, it is considered preferable to use a mixed solution of dichloromethane / ethanol which imparts porosity to the fibers forming the nonwoven fabric.

Example 5 A racemic copolymer of D-lactic acid and L-lactic acid (D / L = 50/50) having a viscosity average molecular weight (Mv) of 210,000 was prepared in the same manner as in Example 1. Thickness 90
A nonwoven fabric of ~ 110 µm was prepared and used as a base material.
The copolymer of p-dioxanone (DOX) having a weight-average molecular weight of 15,000 and D, L-lactide (D, L-LA) prepared in Example 3 was added with u-HA (particle diameter: 2 to 3 μm).
m) was mixed with 50 wt%, and a mixture of 5 wt% of hyaluronic acid (molecular weight: 600,000 to 1.2 million) was further used as an adhesive layer to obtain a biodegradable and absorbable adhesive tape having a width of 15 mm.

On the other hand, the above-mentioned p-dioxanone and D, L-
A 15 mm wide biodegradable and absorbable pressure-sensitive adhesive tape was prepared in which a pressure-sensitive adhesive layer obtained by mixing only u-HA with a copolymer with lactide was formed on one surface of the nonwoven fabric.

Then, with respect to these adhesive tapes,
The adhesion to SUS 304 and the adhesion to cortical bone cut from bovine femur were measured at 37 ° C. according to the 90 ° peel test method of IS Z 0237-1991 (however, the width of the sample was 15 mm and the length was 100mm,
The tensile speed was 300 mm / min). Table 6 shows the results.
Shown in

[0080]

[Table 6]

From these results, it can be seen that the pressure-sensitive adhesive tape in which 5% by weight of hyaluronic acid is mixed in the pressure-sensitive adhesive layer has an increased adhesive force even in the presence of water, such as cortical bone, and thus has both water sensitivity. It was found that the adhesive tape could be a biodegradable and absorbable adhesive tape.

[0082]

As is apparent from the above description, the medical biodegradable and absorbable adhesive tape of the present invention can be used during surgery.
Since the reduction and fixation of the fractured part, the fixation of other tissues, and the temporary fixation can be performed with a simple taping work, the efficiency of the operation is greatly improved, and the time required for the operation can be significantly reduced. After healing, it is absorbed by the living body and disappears, so that reoperation for removing the adhesive tape is not required, and the burden on the patient can be reduced. In particular, it is extremely effective for application to a case in which the tape itself does not require high strength, such as reduction fixation after skull osteotomy such as stenosis.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C060 LL13 MM24 4C081 AA03 AA14 AC03 BA16 BB04 CA052 CA171 CA182 CB011 CC01 CD022 CD042 CD082 CD092 CD122 CD152 CF21 DA02 DA05 4C097 AA01 BB01 CC02 DD02 EE08 FF01 FF03

Claims (12)

[Claims] 1. A method in which at least one surface of a tape substrate made of a biodegradable and absorbable polymer has a temperature close to body temperature (about 30 ° C.
A pressure-sensitive adhesive layer composed of a heat-sensitive biodegradable absorbent material that develops or increases adhesiveness at a temperature of 40 ° C. or higher, or a water-sensitive in vivo material that develops or increases adhesiveness upon contact with moisture A biodegradable and absorbable adhesive tape for medical use, wherein an adhesive layer made of a decomposable and absorbable adhesive is formed. 2. The pressure-sensitive adhesive tape according to claim 1, wherein the tape substrate is any one of a nonwoven fabric, a woven fabric, and a film of a biodegradable and absorbable polymer. 3. The biodegradable and absorbable polymer constituting the tape base material is any one of polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, and lactic acid-caprolactone copolymer, or two kinds thereof. The pressure-sensitive adhesive tape according to claim 1 or 2, which is a mixture of the above. 4. The pressure-sensitive adhesive tape according to claim 1, wherein the biodegradable and absorbable polymer constituting the tape substrate is a copolymer of D-lactic acid and L-lactic acid. 5. The pressure-sensitive adhesive tape according to claim 1, wherein the biodegradable and absorbable polymer constituting the tape substrate is a racemic copolymer of D-lactic acid and L-lactic acid. 6. The pressure-sensitive adhesive tape according to claim 1, wherein the pressure-sensitive adhesive layer, or both the pressure-sensitive adhesive layer and the tape substrate, contain a bioactive ceramic powder. 7. The heat-sensitive biodegradable and absorptive adhesive is p-type
7. A copolymer of dioxanone and another biodegradable and absorbable monomer, having a weight average molecular weight of 2,000 to 200,000. The adhesive tape as described. 8. The heat-sensitive biodegradable and absorbable adhesive substance,
P having a weight average molecular weight of 5,000 to 60,000
A copolymer of dioxanone and D-lactic acid, from 5,000 to
A copolymer of p-dioxanone and L-lactic acid having a weight average molecular weight of 60,000, 5,000 to 60,000
P-dioxanone having a weight average molecular weight of D, L-
Copolymer with lactic acid, copolymer of p-dioxanone having a weight average molecular weight of 8,000 to 50,000 and trimethylene carbonate, 10,000 to 100,000
Any of a copolymer of p-dioxanone and ε-caprolactone having a weight average molecular weight of
The pressure-sensitive adhesive tape according to any one of claims 1 to 6, wherein the pressure-sensitive adhesive tape is a mixture of at least one species. 9. The heat-sensitive biodegradable and absorptive adhesive is p-type
The pressure-sensitive adhesive tape according to any one of claims 1 to 6, which is a copolymer of -dioxanone and meso-D, L-lactide, which has a weight average molecular weight of 5,000 to 60,000. . 10. The copolymer according to claim 7, wherein the copolymer is a star copolymer synthesized by mixing a polyfunctional alcohol such as glycerin, polyglycerin, pentaerythritol, or star polyethylene glycol. An adhesive tape according to any one of the above. 11. An adhesive layer comprising a heat-sensitive biodegradable and absorbable adhesive, wherein glycerin or a polymer thereof, polyvinyl alcohol, hyaluronic acid, alginic acid (soda) or a polymer thereof, polyethylene glycol, chitosan,
The pressure-sensitive adhesive tape according to any one of claims 1 to 10, wherein one or more of oxidized cellulose fibers and microfibrillar collagen are contained to impart water sensitivity. 12. The water-sensitive biodegradable and absorbable adhesive substance,
Fibrin glue, gelatin adhesive, chitosan adhesive,
The pressure-sensitive adhesive tape according to any one of claims 1 to 6, wherein the pressure-sensitive adhesive tape is a collagen-based pressure-sensitive adhesive or a mixture of two or more thereof.