JP3503045B2 - Shape memory biodegradable absorbent material - Google Patents

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 material having a remembered shape, which is restored to its original shape by reheating and decomposed and absorbed in a living body.

[0002]

2. Description of the Related Art Materials (implant materials) used by being implanted in a living body include metals, bioceramics, polymer materials, living body-derived materials, and hybrid materials thereof.

These are so-called absorptive materials which are gradually decomposed after being functioned in the living body, absorbed into the body and discharged out of the body, and non-absorbable materials which are not decomposed in the body but remain as they are. It can be divided into sex materials.

A non-absorbable artificial material (synthetic material) is an undesirable foreign substance when it remains in the body for a long period of time because of the difference in physical and chemical (physiological) properties from the living body or the manifestation of toxicity due to corrosion. Because there is a fear of causing a reaction,
Occasionally, excision site is removed by re-operation. Since this gives the patient the pain of double surgery and further burdens the financial aspect, it is desired to develop a biomaterial that does not require re-operation if necessary.

Biomaterials that can be biodegradable and absorbable in response to these requirements, but have all of these physical properties to the extent that they replace all non-absorbable implant materials such as metals, ceramics, and polymers. Since there are not various absorptive materials, researches and developments have been made to replace them one by one.

Surgical threads for surgery and metal materials (stainless steel, titanium, silver, platinum) for stopping broken or cut parts of a living body are biomaterials left in the living body after surgery. The selection of the suture thread is determined in consideration of tissue damage, tissue tensile strength, fear of suture complications, the influence of body fluid on the suture thread, and the presence of infection.

Generally, silk thread is used for anastomosis of fascia or peritoneum, nylon thread is used for skin or nerve, polyester thread is used for heart or tendon, and polypropylene thread is used for anastomosis of nerve or blood vessel. Synthetic absorbable sutures (polyglycolic acid type) are often used not only in these areas but also in the digestive tract and the like.

However, a wire (metal wire) such as stainless steel or titanium is used for a portion requiring high strength. However, the use of this metal material has rapidly increased recently as a means for observing the state of surgery and the healing state of the affected area after surgery.
ic Resonance Images) or CT (Compputer Tomog
In contrast to raphy), a photo halation phenomenon occurs due to the reflected light rays, which hinders image diagnosis. This fact requires the development of new materials for suturing, anastomosis or ligation to replace metal wires.

The above-mentioned various sutures are variously used in the field of surgery, but in many cases, they are used for work for hemostasis, suturing of incision site and anastomosis other than the center of surgery. To be However, in some cases, the time required for this work often occupies most of the operation time, and therefore there is a demand for the development of suture, anastomosis, and ligation materials that can be treated by a simpler method.

[0010] For example, a method in which a suture is used to sew a cut tendon has been adopted, but the method tends to become more and more complicated. Therefore, an alternative joining material and a simple method are used. Is desired. In addition, at least 50 or more blood vessels are often cut in a surgery of a region such as a chest cavity or abdominal cavity, and it is necessary to suture or ligate at least 100 times for hemostasis or to ligate this after surgery. So
It is desired to develop methods and materials that can be treated more easily. Moreover, conventional non-resorbable materials allow the blood vessels to regenerate naturally after connecting the blood vessels, and to reopen the living body to remove metal clips and staples or various sutures. Because of the complexity and danger of
In addition, because of the dilemma of having to re-suture after making an incision, it is usually left in the living body. Therefore, if the material used for this purpose is a biomaterial that is decomposed and absorbed in the living body and discharged to the outside of the body,
Ideally, these problems can be avoided.

For this purpose, a biodegradable and absorbable polymer such as polyglycolic acid, polylactic acid, a glycolic acid-lactic acid copolymer and polydioxanone is used.
Pulls and clips are made in a special shape in consideration of the physical strength of the polymer, and are devised so that they can be physically caulked using a special jig, and are used in the field of surgery. However, since these are complicated to handle and their physical strength does not reach metal, they have to be considerably larger in size than those made of metal, and they are not ductile like metals. So it has the drawback of not being able to firmly crimp.

[0012]

DISCLOSURE OF THE INVENTION The present invention has been devised in order to respond to the above-mentioned actual circumstances, and is a medical prosthesis material,
In addition to filling materials or materials for scaffolds, ligation (hemostatic) or anastomoses of cut blood vessels, suturing of incision sites,
It is possible to perform ligation, anastomosis, suture, fixation, joining and other treatments of biological tissues such as joining of cut tendons, fixing of broken bones, joining, etc. very easily and reliably, and halation phenomenon in MRI and CT occurs. In addition, controlled drug release and tissue engineering (tissue eng
An implant material made of a novel biodegradable and absorbable material, which is also effective as a base material for ineering, is hydrolyzed and absorbed in the body even if left in the body. The challenge is to develop.

As the shape memory material, norbornene-based, trans-polyisoprene-based, styrene-butadiene copolymer-based, polyolefin-based, polyester-based, polyurethane-based, polyacrylic-based synthetic polymers, cellulose fibers, protein fibers, etc. Natural polymers have been developed, but these are not materials that are decomposed and absorbed in vivo, but biodegradable and absorbable materials that are recognized as biocompatible materials like the present invention are formed. There is still no practical level example in which it is finished as a memory material and is embedded in a living body for use.

[0014]

The basic shape-memory biodegradable and absorbable material of the present invention that achieves the above-mentioned object is composed of a molded product of lactic acid-based polymer, and the shape thereof exerts an external force when heated above a predetermined temperature. It is characterized in that it is restored to the memorized shape without addition. That is, a glass transition temperature (T
g), the temperature is lower than the crystallization temperature (Tc) (100 ° C. when there is no crystallization temperature) (Tf), and is transformed into a molded article of another shape, and the temperature is lower than the glass transition temperature (Tg) as it is. It is a biodegradable and absorbable material that has been cooled to a fixed shape and fixed in its shape, and when reheated to the deformation treatment temperature (Tf) or higher, the shape is restored to the original molded body having a predetermined shape.

The term "deformation process" as used herein means all processes for changing the shape of a molded body, such as expansion deformation, stretching deformation, compression deformation, bending deformation, twisting deformation, or a composite deformation of these,
Means an operation.

In general, the structural form of a molecular assembly of polymers having shape memory performance is such that the temperature is demarcated at a certain temperature with a stationary phase that acts to suppress the fluidity of the polymer molecules and fix the shape of the molded article. It is composed of a reversible phase that can repeat the phenomena of softening and hardening as the polymer molecules flow and solidify as it goes up and down.

The chemical factors that determine the formation of the stationary phase depend on the type of interaction between individual linear polymer molecular chains, the magnitude and form of the interaction density, or the entanglement of the molecular chains. is there.

The intermolecular chain interaction of the polymer is a covalent bond,
Coordination bond, strong primary bond such as ionic bond, and Coulomb force, hydrogen bond, van der Waals force such as relatively weak secondary bond force. Which of these intermolecular interactions forms the constrained phase (stationary phase) and the fluid phase (reversible phase) depends on the chemical structure and sequence of the monomer forming the polymer, or its stereospecificity. Depends on the unique nature of. Due to the difference in the interaction (bonding force) between the polymer molecular chains, the polymer aggregate forms a rubber phase, a glass phase, and a crystal phase. Then, there are some polymers in which these phases are present alone, and some are in plural.

A polymer having a shape memory property has a property that the elastic modulus greatly changes above and below the glass transition temperature (Tg), so that the shape is memorized by utilizing this property. That is, a molded product (primary molded product) to which a certain shape (original form) is given by a general plastic molding method has a temperature (Tm) higher than the Tg of the polymer and lower than the melting temperature (Tm).
It is heated to f) to soften it and transform it into a shape different from the original shape. While maintaining this shape, it is cooled to a temperature lower than Tg to fix the shape (secondary molded product). After that, the shape at the time of the secondary molding is erased by heating again to the temperature of the secondary molding temperature (Tf) or higher and Tm or lower, and the shape is restored to the original shape which is the primary molded product. The shape memory of the polymer has the ability to be temporarily given a secondary shape by such a process and to return to the original shape again.

At this time, the vitreous polymer showing a large change in elastic modulus above and below the temperature with Tg as the boundary is one of the most effective ones for fixing and erasing another shape and recovering to a certain shape. Is. In other words, it is one of the polymers in which the shape is erased and the shape is restored almost completely. Many of the lactic acid-based polymers used in the present invention have a modulus of elasticity (E ') that changes by 150 times or more with Tg as a boundary, and are therefore suitable as shape memory materials.

The above properties cannot be obtained with a polymer consisting only of a fluid phase, as in the case of only a rubber phase whose reversible phase is more fluid than a glass phase. However, when a rubber phase having a cross-linked portion between molecules alone or a plurality of mixed phases in which a glass phase or a crystal phase is mixed, a polymer having shape memory / recovery performance exists. However, in terms of whether the secondary shaping can be accurately fixed and the shape can be completely restored to its original shape, the function of memory restoration and the temperature of restoration are within the practical range usable for medical applications. There may be some dissatisfaction.

On the contrary, the crystalline phase is a stationary phase, and it is not possible to determine the shape memory performance of a polymer composed of only this phase. A molecular assembly of a polymer consisting of a crystalline phase and a rubber phase (particularly a partially crosslinked rubber phase) at room temperature,
Alternatively, even in the case of a polymer molecular assembly in which a crystal phase and a glass phase are mixed, there are those that exhibit shape memory performance.

Of the biodegradable and absorbable polymers, a typical polymer that has excellent biocompatibility, safety, is recognized for use in vivo, and has practical experience as an implant material. There are several poly (α-oxy acids). Polyglycolic acid has a Tm
(Melting temperature) is 230 ° C (225 to 235 ° C), Tg is 36 ° C (45 to 50 ° C), and poly-L-lactic acid has Tm of 18
It is a polymer having crystallinity (having a crystallization temperature) of 9 ° C (195 ° C) and Tg of 56 ° C (55 to 65 ° C). However, the values in parentheses are from different documents.

These polymers are basically composed of a crystalline phase and an amorphous phase (glass phase), and although they can be made completely amorphous depending on the heat treatment method, they have a fluidity such that they can be molded by heating. It is unavoidable to settle into a crystalline (partly amorphous glass phase is mixed) polymer in the process of giving (forming) (deforming). This is the chemical structure of the monomer (consisting of the same isomer), which is the unit of the constituent molecules of the polymer.
These polymers are essentially crystalline polymers because they are an inevitable phenomenon.

Polyglycolic acid and polylactic acid, which are homopolymers, are essentially crystalline polymers, but the substance is a polymer consisting of a crystalline phase and a glass phase, and although the Tg is relatively high, At a temperature higher than Tg and lower than the crystallization temperature (Tc, Tc <Tm), the shape can be memorized by performing the above-mentioned deformation treatment for secondary shaping and solidifying by cooling. However, the temperature at that time requires a high temperature of, for example, 100 ° C. or more because the crystal phase is mixed, and the crystallization progresses during the treatment to increase the crystallinity, so that the shape recovery is 100%. Since it has the drawback of requiring a high temperature of ℃ or more and incomplete recovery, it may not be said that it can be a practical shape memory polymer (especially as a medical implant). I don't know.

In lactic acid, S (L) and R which are optical isomers
(D) I have a body. Polylactic acid is usually synthesized by a method of forming an oligomer from these lactic acids, then forming a cyclized dimer (lactide), and further ring-opening polymerizing this to give polylactic acid. The above-mentioned poly-L-lactic acid (or poly-D-) made from only L-form (or D-form) of lactic acid
Lactic acid) is an essentially crystalline polymer due to its stereospecificity, and its molecular chain has an α-helix structure.

The cyclized dimers of lactic acid are L-form and L-form, D-form and D-form, and L-form and D-form are difficult to extract and separate in practice.
There are three types of lactide consisting of the body (meso body). These are L-lactide, D-lactide and DL (meso)-, respectively.
Called lactide. Poly-D, L-lactide (poly-D, L-lactic acid) can be synthesized by mixing L-lactide and D-lactide in a predetermined ratio and ring-opening polymerization, but the ratio is 5
A polymer of D-form and L-form mixed at 0/50 (molar ratio) is usually referred to as poly-D, L-lactic acid. But,
Those having different ratios are also poly-D, L-lactic acid in a broad sense.

When the ratio of the D-form and the L-form is different, the lactide having the larger ratio becomes a factor to form a segment which is a block-connected portion. L-lactide and D
-The shortest monomer-linking unit of poly-D, L-lactide in which lactide is linked in an equimolar ratio is-(L-LD-
D)-, and the minimum unit of the connection of such optical isomers disturbs the interaction between polymer molecular chains appropriately, so that it is not possible to form a crystalline polymer like a polymer of L-form or D-form, Creates a glassy polymer at room temperature that is essentially amorphous. The reason why it does not form a rubbery polymer is due to the proper balance of polar and non-polar chemical structure of the lactic acid monomer. The T of poly-D, L-lactic acid in which the ratio of the D-form to the L-form is 50/50 (molar ratio)
g is 57 ° C (55 to 60 ° C).

The present invention pays attention to the chemical structure and sequence of poly-D, L-lactic acid, the phase structure, the value of Tg, the physical properties and the properties of decomposition and total absorption in the living body, It has been completed for the purpose of practical use as an implant material that can be implanted in the living body, considering its effectiveness as a biodegradable and absorbable shape memory material.

The present invention is based on the recognition and understanding of the following facts. That is, a molded body made of a lactic acid-based polymer containing poly-D, L-lactide as a basic component has a structural portion (stationary phase) that prevents fluidity and fixes the shape of the molded body, and a glass transition temperature of the polymer ( It has a structural part (reversible phase) in which curing and softening are repeated by raising and lowering the temperature at Tg). Therefore, after melting the original product, Tg
By cooling below, the stationary phase and the reversible phase are fixed and the shape (original shape) of the primary molded body is maintained. When this primary compact is heated again to a temperature (Tf) higher than Tg and lower than Tc to be deformed, only the reversible phase flows and can be transformed into a compact having another shape. When this is cooled to room temperature below Tg as it is, the reversible phase is fixed and a shaped product (secondary shaped product) different from the original form is obtained. When such a secondary compact is heated again to a temperature of Tf or higher (Tc or lower), the reversible phase flows again, and the original shape (the original shape of the primary compact) memorized by the stationary phase is restored. .

In this case, the lactic acid-based polymer preferably has a shape recovery temperature in the range of 45 to 100 ° C. That is, the lactic acid-based polymer having a Tg of 45 to 100 ° C.
It is useful as a biodegradable and absorbable implant material to be used by being implanted in a living body. The limitation of this temperature range is as follows.

In general, medical materials made of plastic and requiring sterilization are generally sterilized by ethylene oxide gas (EOG), though some sterilization by γ-ray is possible except for a small number of heat-resistant polymer materials. Since the lower limit temperature of EOG sterilization is 40 to 45 ° C, it is necessary to have a temperature at which the shape does not recover at the temperature during sterilization. Also, because the product must not regain its shape during storage and storage, it is necessary to select a polymer having a Tg of 45 ° C. or higher, which is the lower limit of the temperature that can withstand the summer temperature as much as possible.

On the other hand, the upper limit of the high temperature range is determined by the heat treatment for recovering the shape in the living body. When the secondary molded body is embedded in a living body and heated to restore it to its original shape by heat treatment, a method such as laser, ultrasonic wave, high frequency wave, infrared ray, or a direct heating method using a heat medium such as hot air or hot water is used. However, since it is necessary that the living tissue does not get burned at this time, it must be heated at a temperature as low as possible. If heating is performed for a short time within a few seconds, there is little risk of burns even when the heating medium comes into contact with 100 ° C. Therefore, this temperature can be set as the upper limit. However, it is better that the shape can be recovered more safely by heating at 45 to 70 ° C., preferably 50 to 65 ° C. Therefore, the range of the shape memory recovery temperature is 45 to 10
The temperature was set to 0 ° C.

Among the lactic acid type polymers, the most preferable one is poly-D, L-lactic acid described above. The poly-D, L-lactic acid may be a copolymer obtained by ring-opening polymerization of a mixture of D-lactide and L-lactide in different ratios, and may be obtained by ring-opening polymerization of DL-lactide. It may be a copolymer, a copolymer obtained by polymerizing a mixture of L-lactic acid and D-lactic acid, or a mixture of these copolymers.

Since such poly-D, L-lactic acid is basically a non-crystalline glassy polymer, it exhibits elastic characteristics that can be easily deformed at a temperature higher than the glass transition temperature, and is expanded and stretched at a high magnification. Deformation, compression deformation, twisting deformation, etc. are possible, and the degree of shape restoration (shape recovery rate) is almost 100%, and the strength can be adjusted mainly by the intervention of the molecular weight and some crystal phase. Further, since it is amorphous, it has an advantage that hydrolysis in vivo is faster than that of crystalline poly-L-lactic acid.

In addition, vitreous amorphous poly-D, L-
A part of biodegradable and absorbable polymer such as poly-L-lactic acid, poly-D-lactic acid, polyglycolic acid or amorphous polydioxanone, polycaprolactone, polytrimethylene carbonate which is crystalline with respect to lactic acid is mixed. May be. Further, lactic acid-glycolic acid copolymer, lactic acid-dioxanone copolymer, lactic acid-caprolactone copolymer, lactic acid-ethylene glycol copolymer, lactic acid-propylene copolymer, lactide-ethylene oxide / propylene oxide copolymer (however , Lactic acid and lactide are L-, D-, D
L-, D, or L-) may be used alone to obtain a polymer having an essentially amorphous shape memory recovery property, which is obtained by copolymerizing a lactide with a monomer having biodegradability and absorbability. Alternatively, they can be mixed and suitably used.

The advantages of using such a crystalline homopolymer as a mixture are that various physical strengths as a material can be increased, deformation and memory shape recovery temperatures can be increased, and decomposition in vivo can be prevented. It is possible to adjust the speed and the time required for total absorption. In addition, the advantage of copolymerizing an absorptive monomer in the molecule is that the crystalline polymer is made amorphous by disturbing the cycle of the chemical arrangement of the monomer in the molecular chain and disturbing the interaction between the molecular chains. Since they can be changed, it is possible to impart shape memory recovery performance with their respective characteristics and to adjust the rate of decomposition / absorption.

Another technical proof of the present invention is that the temperature of secondary shaping is such that these biodegradable and absorbable polymers do not deteriorate during molding. These polymers are easily deteriorated when they are molded at Tm or higher by usual molding methods such as injection molding, extrusion molding, and compression molding. For example, a polymer having a molecular weight of 400,000 at the beginning is usually reduced to a molecular weight of 1/10. However, the Tf of the present invention causes almost no deterioration. Therefore, the shape recovery rate to the original shape becomes extremely high, and a material having a good shape memory can be obtained.

The above materials have various shapes such as a cylindrical shape, a ring shape, a thread shape, a rod shape, a plate shape, and an irregular shape, which are shapes to be memorized, that is, the shape of the original molded body, depending on the site used in the living body and the purpose of use. By determining and deforming this into another shape that is easy to use, for example, a vascular ligation material, a vascular anastomosis material, a tendon-bonding material, a bone-bonding material, which will be described later,
It can be suitably used as a suture material, a vascular restenosis preventing material, a bone cement outflow preventing material in the medullary canal, and other living tissue treating materials. Moreover, since this material consists of a biodegradable and absorbable lactic acid-based polymer, even if it is left in the body, it will be hydrolyzed over time, absorbed into the body, and discharged outside the body, so it will remain as a foreign substance. There is no. Further, the non-metal lactic acid-based polymer does not cause the MRI or CT halation phenomenon.

The above shape memory biodegradable and absorbable material is
Although the original molded body made of lactic acid-based polymer is subjected to the deformation treatment only once, the deformation treatment may be repeated again. That is, a molded product of a predetermined shape made of a lactic acid-based polymer is deformed into a molded product of another shape at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature), and as it is. After cooling to a temperature lower than the glass transition temperature and fixing its shape, this molded body is deformed into a molded body of another shape at a temperature higher than the glass transition temperature and lower than the above deformation treatment temperature, and the glass transition is performed as it is. A biodegradable and absorbable material having a fixed shape by cooling to a temperature lower than the temperature may be used.

Such a shape memory biodegradable and absorbable material was subjected to the first deformation treatment when the temperature of the shape memory material exceeded the second deformation treatment temperature in the middle of reheating. When the shape of the subsequent molded body is restored, and when the temperature of the shape memory material becomes equal to or higher than the initial deformation processing temperature, the shape is finally restored to the original molded body having a predetermined shape. Therefore, this shape memory material has an advantage that the shape restoration in the intermediate stage can be effectively utilized.

In the shape memory biodegradable and absorbable material of the present invention, a solid (dense) molded body of a lactic acid polymer molded by melt molding or other various molding means is used as the original molded body. However, a porous foamed molded product is also preferably used. Such a porous molded article is substantially free of another shape at a temperature (Tf) higher than its glass transition temperature (Tg) and lower than its crystallization temperature (Tc) (100 ° C. when there is no crystallization temperature). The biodegradable and absorbable material in which the shape is fixed by deforming (for example, compressing and deforming) the porous molded body and cooling it to a temperature lower than the glass transition temperature as it is to the above deformation processing temperature (Tf) or higher. When heated again, the shape is restored to the original porous body having a predetermined shape. Thus, when the biodegradable and absorbable material is restored to the original porous molded body and embedded in the living body, the body fluid penetrates into the material through the continuous pores and the material is rapidly hydrolyzed. On the other hand, since the tissue cells of the surrounding tissue enter the material through the pores and grow together with the body fluid, the material replaces the tissue cells and disappears within a relatively short period of time. Therefore,
This material can be suitably used as a scaffold for tissue reconstruction.

The original porous molded body has a foaming ratio of 2 to 3
A material having a porosity of about 50 to 70% is preferably used. A shape memory material obtained by subjecting a molded body having a foaming ratio lower than 2 times to a deformation treatment has insufficient penetration of body fluid or tissue cells into the material even if it is restored and embedded in a living body. A shape memory material obtained by subjecting a molded body having a foaming ratio higher than 3 times to a deformation treatment may have insufficient strength if it is restored and embedded in a defect portion of hard tissue such as bone in a living body. However, this is not the case when applied to soft tissue.

The shape memory biodegradable and absorbable material of the present invention may contain bioactive bioceramic powder and various drugs.

As the bioceramic powder, surface bioactive hydroxyapatite, bioglass or crystallized glass biomedical glass, bioabsorbable wet hydroxyapatite, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate. Powders of octacalcium phosphate, calcite, diopsite and the like are suitable, and these are used alone or in combination of two or more kinds. The shape memory biodegradable and absorbable material containing such bioceramics powder, when embedded in the bone tissue in the living body, the bone tissue is induced and formed on the material surface by the bioceramics powder, and the bone tissue becomes Since it is bonded and fixed or replaced, it can be suitably used as a bone-bonding material. In particular, a shape memory material obtained by compressing and deforming the above-mentioned porous molded body containing bioceramic powder is a bone tissue. It is extremely effective for reconstruction.

On the other hand, as the drug, in addition to various therapeutic agents, antibacterial agents, bone growth factors, various hormones, physiologically active substances, various cytokines, etc. are used. Such a shape-memory biodegradable and absorbable material containing a drug can be devised so that the drug can be released at a substantially constant rate when implanted in a living body, and thus is suitable as a base material for DDS (Drug Deliverly System). Can be used. The shape memory material containing the growth factors such as bone growth factors and cytokines is extremely effective especially as a material for osteosynthesis or bone tissue reconstruction.

Next, specific embodiments of the shape memory biodegradable and absorbable material of the present invention will be described in detail with reference to the drawings.

[0048]

1 is an explanatory view of a shape memory biodegradable and absorbable material for blood vessel anastomosis (hereinafter referred to as a shape memory material for blood vessel anastomosis).

The shape memory material 1 for blood vessel anastomosis is made of the above-mentioned cylindrical shaped body of lactic acid-based polymer,
It is a material whose shape is restored to a memorized small-diameter cylindrical shape even when an external force is not applied, when heated above a predetermined temperature (deformation processing temperature (Tf) described later).

That is, the shape memory material 1 for blood vessel anastomosis is
A small-diameter cylindrical molded body 1a made of lactic acid-based polymer
Crystallization temperature (T) higher than its glass transition temperature (Tg)
c) Radial expansion at a temperature (Tf) lower than (100 ° C when there is no crystallization temperature) to form a large diameter cylindrical shape, and then cooled to a temperature lower than the glass transition temperature (Tg) at room temperature. By fixing the large-diameter cylindrical shape, the small-diameter cylindrical shape of the original molded body 1a is memorized.

The original compact 1a having a cylindrical shape has a temperature at which the lactic acid-based polymer can be thermoformed (a softening temperature (Ts) when there is no melting point, and a melting temperature (Tm) or higher when there is a melting point). By heating and molding into a small-diameter cylindrical shape (tube shape) by a molding means such as an extruder, and then cooling and solidifying at room temperature, the small-diameter cylindrical shape is fixed. Both the stationary phase and the reversible phase are solidified. There is. The inner diameter of the small-diameter cylindrical molded body 1a needs to be set smaller than the outer diameter of the blood vessel, and it is appropriate to set the inner diameter according to the thickness of the blood vessel to be anastomosed. Further, if the thickness of the molded body 1a is about 0.5 to 3 mm, the strength is sufficient.

Various means can be adopted as a means for expanding and deforming the molded body 1a, but the simplest means is to heat the molded body 1a to the above deformation processing temperature (Tf) while sharpening the tip. Expansion rod 1 made of metal or synthetic resin
This is a method in which 01 is expanded through the molded body 1a. The deformation ratio (expansion ratio of the inner diameter) of the molded body 1a can be up to about 15 times, but if the ratio is too high, the lactic acid-based polymer becomes fibrillated or heterogeneous depending on the polymer composition, and conversely the ratio is low. If it is too much, the effect of restoring the shape becomes insufficient, so it is desirable to make the ratio approximately 1.3 to 10 times. A more preferable range of the deformation magnification is about 1.5 to 6 times.

In order to memorize the small-diameter cylindrical shape of the original molded body 1a, it is necessary to perform the expansion deformation treatment at a temperature (Tf) higher than the glass transition temperature (Tg) and lower than the crystallization temperature (Tc). However, most of the lactic acid-based polymers used in the present invention have a glass transition temperature (Tg) in the range of 45 to 70 ° C., and for the reason described above, the temperature (Tf) for extended deformation treatment is 100 at the highest. Up to ℃. Usually 50 ~
Extended deformation processing is performed at a relatively low deformation processing temperature of about 75 ° C.

As described above, when the expansion rod 101 is inserted while heating the small-diameter cylindrical shaped body 1a to a deformation treatment temperature (Tf) higher than the glass transition temperature (Tg) and lower than the crystallization temperature (Tc), Since only the reversible phase of the molded body 1a is melted and the polymer itself is softened to the extent that it can be molded apparently, it can be expanded and deformed into a large diameter cylindrical shape. Then, when it is cooled at a normal temperature lower than the glass transition temperature (Tg) while being expanded and deformed, the reversible phase is solidified again, and the shape memory material 1 for blood vessel anastomosis in which the shape is forcibly fixed in a large-diameter cylindrical shape is obtained. When such a large-diameter cylindrical shape memory material 1 for blood vessel anastomosis is heated again to the deformation treatment temperature (Tf) or higher, only the reversible phase is melted and the stationary phase is transformed into the original small-diameter cylindrical shaped body 1a. The shape is quickly restored. However,
The stationary phase and the reversible phase are not limited to those forming an independent block phase, and may have a structural form showing a similar function without forming a phase structure due to interaction between molecules.

The shape memory material 1 for blood vessel anastomosis is finally gas sterilized and stored, but as described above, a lactic acid-based polymer having a glass transition temperature within the range of 45 to 70 ° C. is used. So, the temperature at the time of gas sterilization (40-45 ℃)
There is no risk that the shape will be restored by or will be restored during storage.

FIG. 2 shows the shape memory material 1 for vascular anastomosis described above.
It is explanatory drawing of the usage method of.

First, the cut blood vessels 102, 10
The ends of 2 are inserted from both end openings of the large-diameter cylindrical shape memory material 1 for blood vessel anastomosis, and then the shape memory material 1 for blood vessel anastomosis is heated again to the above deformation treatment temperature (Tf) or higher.
As a means for reheating, a means for contacting by blowing hot air or warm water (sterilized physiological saline or the like) having a temperature above the deformation treatment temperature (Tf) onto the shape memory material 1 for vascular anastomosis is convenient. However, other means such as laser heating, high frequency heating, ultrasonic heating, infrared heating and the like can also be adopted.

When reheated in this manner, the large-diameter cylindrical shape memory material 1 for blood vessel anastomosis promptly (within a few seconds) restores the shape to the original small-diameter cylindrical shaped body 1a, and both blood vessels 102, 102 are formed. Since the ends of the blood vessels are held and fixed, the blood vessels 102 and 102 can be anastomosed very easily.
Therefore, compared to the conventional case where a blood vessel is sewn together with a suture, the anastomotic procedure for the blood vessel is extremely simple and easy, and the efficiency of the operation can be significantly improved.
Moreover, since the reheating temperature is not high and the heating time is as short as several seconds, there is no risk of burning the blood vessels and surrounding tissues, and it is safe.

In some cases, after the shape of the shape-memory material 1 for vascular anastomosis is restored by reheating, the shape-memory material 1 for vascular anastomosis is cautiously flattened by a suitable caulking jig to cool and solidify. You may do it. By doing so, there is an advantage that the holding and fixing force of the blood vessel by the shape memory material for blood vessel anastomosis 1 is further improved. Further, before restoring the shape memory material 1 for blood vessel anastomosis, an adhesive such as fibrin glue is applied to the inner surface of the material 1 and the material 1 is restored by reheating.
The blood vessel 102 or the blood vessels 102 may be adhered to each other.

When the blood vessels 102, 102 are anastomosed using the shape memory material 1 for blood vessel anastomosis as described above, the blood vessels are connected by natural healing. After that, the shape memory material 1 for blood vessel anastomosis is hydrolyzed over time due to contact with body fluid, and is eventually absorbed into the body and completely disappeared. Although its speed depends on the type of polymer, poly-D, L-lactic acid decomposes considerably faster than poly-L-lactic acid, and is suitable for this application.

Shape memory material 1 for blood vessel anastomosis of this embodiment
Is the original small-diameter cylindrical shaped molded body 1 by means of melt extrusion molding.
Although a is manufactured, it may be manufactured by other melt molding means such as injection molding. Further, a polymer solution in which a lactic acid-based polymer is dissolved in a volatile solvent is applied or sprayed around the core material to form a thick cylindrical film around the core material, and after the solidification is dried and solidified, the core material is extracted and molded body 1a. May be produced. When the molded body 1a is produced by applying or spraying the polymer solution in this manner, the drug or the like can be blended in the polymer solution without being deteriorated by heat, so that the shape memory material 1 for blood vessel anastomosis containing the drug or the like is obtained. It is especially effective when you want to.

A polymer solution prepared by dissolving a lactic acid-based polymer in a mixed solvent of a solvent capable of dissolving the lactic acid-based polymer and a non-solvent having a boiling point higher than this solvent is used as the above solvent. When the core material is applied or sprayed and dried, a small-diameter cylindrical porous foam molded body 1a having open cells is obtained. Shape memory material 1 for blood vessel anastomosis obtained by subjecting such a foamed molded body 1a to an expansion deformation process
When the foamed body 1a was reheated to restore its original shape and was embedded in the living body with the blood vessels anastomosed, the body fluid penetrated into the memory material 1 through continuous bubbles and had continuous pores. Since the contact area with the body fluid is significantly increased as compared with the case where there is no one, it has an advantage that the hydrolysis proceeds rapidly and is absorbed into the body in about 1 to 3 months.

In this embodiment, both the original molded body 1a and the shape-memory material 1 subjected to the expansion and deformation treatment are formed in a cylindrical shape having a perfect circular cross section, but the invention is not limited to this, and for example, It is possible to form a tubular shape having various cross sections such as an elliptical shape, a polygonal shape of a triangle or more, and an irregular shape.

FIG. 3 is an explanatory view of a shape memory material for blood vessel anastomosis according to another embodiment of the present invention.

In the shape memory material 2 for blood vessel anastomosis, the original small-diameter cylindrical shaped body 2a made of lactic acid-based polymer has an inner surface 21a having irregularities, and this shaped body 2a has a glass transition temperature (Tg). Expanded and deformed into a large-diameter cylindrical shape at a higher deformation temperature (Tf) lower than the crystallization temperature (Tc) (100 ° C. when there is no crystallization temperature), and then directly lower than the glass transition temperature (Tg). The large diameter cylindrical shape is fixed by cooling.

When such a shape memory material 2 for vascular anastomosis is used to restore the shape by reheating in the same manner as described above and the blood vessel is anastomosed, the original small-diameter cylindrical shaped body 2a has an uneven inner surface 21a. Because of having this uneven inner surface 21
This makes it possible to firmly hold and fix the blood vessel from the surroundings. Therefore, there is no concern that the blood vessel will come out of the blood vessel anastomosing material 2.

It should be noted that the unevenness is formed by a small-diameter cylindrical shaped body 2a.
Not only in the long axis direction, but also in the direction perpendicular to the inner surface of the molded body 2a, fold-shaped irregularities may be formed so that both ends of the blood vessel cut at the time of reheating can approach and come into contact with each other easily.

FIG. 4 is an explanatory view of a shape memory material for blood vessel anastomosis according to still another embodiment of the present invention, and FIG. 5 is an explanatory view of a method of using the same shape memory material.

The shape memory material 3 for blood vessel anastomosis comprises a small-diameter cylindrical shaped body 3a made of a lactic acid-based polymer, which has a crystallization temperature (Tc) higher than its glass transition temperature (Tg) (when there is no crystallization temperature). At a deformation treatment temperature (Tf1) lower than 100 ° C., a small diameter cylindrical shaped body 3b longer than the shaped body 3a is stretched and deformed, and then cooled to a temperature lower than the glass transition temperature to fix the shape. Furthermore,
This molded body 3b is subjected to a deformation treatment temperature (Tf) higher than the glass transition temperature (Tg) and lower than the above deformation treatment temperature (Tf1).
In 2), it was expanded and deformed into a large-diameter cylindrical shape, then cooled to a temperature lower than the glass transition temperature and the shape was fixed.

The shape memory material 3 for blood vessel anastomosis as described above is
When reheated at a temperature equal to or higher than the first deformation treatment temperature (Tf1), a long small-diameter cylinder is reached when the temperature of the shape memory material 3 exceeds the second deformation treatment temperature (Tf2) in the middle of reheating. The shape is restored to the shaped body 3b, and the temperature of the shape memory material 3 is changed to the first deformation processing temperature (Tf).
1) When the above is reached, the shape is finally restored to the original small-diameter cylindrical molded body 3a.

Therefore, as shown in FIG. 5, when the blood vessels 102, 102 are inserted from both end openings of the shape memory material 3 for blood vessel anastomosis and reheated, first, the shape memory material 3 contracts in the radial direction. Long, small diameter cylindrical shaped body 3
Then, the blood vessels 102, 102 are strongly held and fixed in this way, and the blood vessels 102, 102 are further strongly held and fixed, and further contracted in the longitudinal direction to form the original compact body 3a having a small diameter. The shape is restored, and both blood vessels 102, 102 can be anastomosed in a state of being pulled together.

It is desirable to set the second deformation treatment temperature (Tf2) lower than the first deformation treatment temperature (Tf1) by 10 ° C. or more. If the temperature difference between the two is less than 10 ° C., the above-mentioned vascular anastomosis is performed. When the shape memory material 3 is reheated, the restoration to the molded body 3b and the restoration to the molded body 3a will proceed almost at the same time, and it will be difficult to hold and hold the blood vessels 102, 102 and then draw them. Become. On the other hand, when the temperature difference between the two is 10 ° C. or more, during reheating, the time from when the temperature of the memory material 3 exceeds the deformation processing temperature (Tf2) to when it reaches the deformation processing temperature (Tf1). Since the restoration to the molded body 3b is completed, the restoration to the molded body 3b and the restoration to the molded body 3a occur stepwise, and the blood vessel 10
It is possible to hold and fix the 2, 102 and then draw them together for anastomosis. The more preferable temperature difference between the first deformation treatment temperature (Tf1) and the second deformation treatment temperature (Tf2) is 20 to 3.
It is 0 ° C. A material suitable for this example is a lactic acid-based polymer having a part of a crystalline phase or a part of a mixture of crystalline lactic acid-based polymers.

Also in the shape memory material 3 for blood vessel anastomosis, a molded body having an uneven inner surface is used as the original molded body 3a having a small diameter cylinder, and when the shape is restored by reheating, there is unevenness. It is desirable to be able to hold and fix blood vessels more strongly on the inner surface.

FIG. 6 is an explanatory view of a shape memory biodegradable and absorbable material for blood vessel ligation (hereinafter referred to as a shape memory material for blood vessel ligation) according to still another embodiment of the present invention, and FIG. 7 is a method of using the same. FIG.

The shape-memory material 4 for ligating blood vessels is made of a ring-shaped molded body of lactic acid-based polymer, and its shape does not exert an external force when heated above a predetermined temperature (deformation processing temperature (Tf) described later). However, it is a material that is restored to the memorized small diameter ring shape.

That is, the shape memory material 4 for ligating blood vessels is
Small-diameter ring-shaped molded body 4a made of lactic acid-based polymer
Is expanded and deformed into a large-diameter ring shape at a deformation treatment temperature (Tf) higher than the glass transition temperature (Tg) and lower than the crystallization temperature (Tc) (100 ° C. when there is no crystallization temperature), and the glass transition is performed as it is. The large-diameter ring shape is fixed at room temperature by cooling to a temperature lower than the temperature (Tg).

Such a large-diameter ring-shaped shape-memory material 4 for ligating blood vessels is promptly reheated at a temperature equal to or higher than the deformation processing temperature (Tf) to promptly produce the original small-diameter ring-shaped molded body 4a.
The shape is restored to. Therefore, as shown in FIG. 7, the shape memory material 4 for vascular ligation is attached to the end of the blood vessel 102 to be ligated.
When it is inserted and contacted with warm air or warm water (sterilized physiological saline) having a deformation treatment temperature (Tf) or higher and reheated, the shape is instantly restored to the original small-diameter ring-shaped molded body 4a and the blood vessel 102. The end of the can be tightened from the surroundings and ligated to stop the bleeding. In that case, if the shape memory material is simultaneously flattened by crimping with a crimping jig or the like to be cooled and solidified, the end portion of the blood vessel 102 can be ligated more strongly, which is safe. If necessary, a hemostatic agent or the like may be applied to the ligated end of the blood vessel 102.

The original small-diameter ring-shaped molded body 4a needs to have a small inner diameter capable of sufficiently tightening and ligating the blood vessel 102. Specifically, in consideration of the thickness of the blood vessel to be ligated, the diameter is 0.1. Molded body 4a having an inner diameter of about 1.5 mm
It is desirable to mold it. In that case, this molded body 4a
If the inner surface of the blood vessel is formed into an uneven inner surface, the blood vessel 102 can be ligated more strongly. It is sufficient that the width of the molded body 4a is about 0.3 to 5 mm.

The expansion deformation processing of the original molded body 4a is performed by a simple means such as inserting the expansion rod 101 into the molded body 4a in the same manner as described above, and a large-diameter ring shape whose inner diameter is about 3 to 10 times is formed. It is desirable that the shape memory material 4 for blood vessel ligation is expanded and deformed. The shape memory material 4 having an expansion ratio of the inner diameter of less than 3 is not easy to fit into a blood vessel, and
The shape memory material 4 having an expansion ratio of more than 0 times is not preferable because it may cause a decrease in strength due to the non-uniformization phenomenon.

In this embodiment, both the original molded body 4a and the shape memory material 4 subjected to the expansion and deformation process are formed in a perfect circular ring shape. However, for example, an elliptical shape, a polygonal shape other than the perfect circular shape, Of course, it may be formed in a ring shape such as an irregular shape.

FIG. 8 is an explanatory view of a shape memory material for blood vessel ligation according to still another embodiment of the present invention.

The shape-memory material 5 for ligating blood vessels comprises a small-diameter cylindrical shaped body 5a made of a lactic acid-based polymer, which has a crystallization temperature (Tc) higher than its glass transition temperature (Tg) (when there is no crystallization temperature). The large-diameter cylindrical shaped body 5b is expanded and deformed at a deformation treatment temperature (Tf) lower than 100 ° C., and cooled to a temperature lower than the glass transition temperature as it is to fix the large-diameter cylindrical shape 5b. Further, it is further sliced into a large diameter ring.

Such a large-diameter ring-shaped shape memory material 5 for ligating blood vessels, when reheated at a temperature equal to or higher than the deformation processing temperature (Tf), has a small-diameter ring shape in which the original small-diameter cylindrical shaped body 5a is sliced. The shape is restored to. Therefore, when the large-diameter ring-shaped shape memory material 5 is inserted into the end portion of the blood vessel and brought into contact with warm air or warm water (sterilized physiological saline) having a temperature higher than the deformation treatment temperature (Tf) and reheated, it is instantly It can be restored to a small-diameter ring shape and the ends of blood vessels can be ligated to stop bleeding.

The inner diameter of the original small-diameter cylindrical shaped body 5a is
0.1 to 1.5 mm considering the thickness of the blood vessel to be ligated
It is desirable to set the degree to some extent, and it is desirable to form the inner surface of the molded body 5a to have an uneven inner surface in order to improve the ligation property of blood vessels. Then, it is desirable that the expansion deformation processing of the molded body 5a is performed so that the molded body 5b has a large-diameter cylindrical shape having an inner diameter of about 3 to 10 times, as described above. It is sufficient that the width dimension of the large-diameter ring-shaped shape memory material 5 in which the molded body 5b is sliced is approximately 0.3 to 5 mm.

FIG. 9 is an explanatory view of a shape memory biodegradable and absorbable material for tendon junction (hereinafter referred to as a shape memory material for tendon junction) according to still another embodiment of the present invention, and FIG. 10 is a method of using the same. FIG.

This tendon-joining shape memory material 6 comprises a flat, substantially rectangular tubular shaped body 6a made of a lactic acid-based polymer having a small opening area and having a crystallization temperature (Tc) (Tc) higher than its glass transition temperature (Tg). At a deformation treatment temperature (Tf1) lower than 100 ° C. when there is no crystallization temperature), a stretch deformation treatment is performed on a substantially rectangular tubular shaped body 6b having a smaller opening area than that of the above-mentioned shaped body 6a, and the temperature is lower than the glass transition temperature. After being cooled to a low temperature to fix its shape, the molded body 6b is heated to a temperature higher than the glass transition temperature (Tg) and the deformation treatment temperature (Tf1).
) At a lower deformation processing temperature (Tf2), the material is expanded and deformed into a substantially rectangular tube shape having a larger opening area, and then cooled to a temperature lower than the glass transition temperature (Tg) to fix the shape.

When such a shape memory material 6 for tendon junction is reheated at a temperature equal to or higher than the first deformation treatment temperature (Tf1), the temperature of the shape memory material 6 is changed to the second temperature during the reheating process. When the deformation processing temperature (Tf2) is exceeded, the shape is restored to the intermediate molded body 6b, and when the temperature of the shape memory material 6 becomes equal to or higher than the initial deformation processing temperature (Tf1), the original molding is finally performed. The shape is restored to the body 6a.

Therefore, as shown in FIG. 10, the band-shaped tendon 10 cut from both ends of the shape memory material 6 for joining tendons.
When 3, 103 are inserted and reheated, first, the shape memory material 6 contracts in the longitudinal and lateral directions, and is restored to the long flat, substantially rectangular tubular shaped molded body 6b having a small opening area, and the tendons 103, 10 are formed.
Hold 3 firmly. Then, the tendons 103 and 103 are contracted further in the lengthwise direction while being strongly held and fixed, and the shape is restored to the original short flat, substantially rectangular tubular shaped molded body 6a having a small opening area. It is possible to join them in a state where 103 is pulled up.

The original molded body 6a needs to have a flat, substantially rectangular tube shape having an inner dimension smaller than the longitudinal and lateral dimensions of the band-shaped tendon 103 so that the band-shaped tendon 103 can be firmly held and fixed. Specifically, it is preferable that the molded body 6a has a flat, substantially rectangular tube shape with an inner dimension of 2 to 10 mm, a width of 7 to 30 mm, and a wall thickness of about 0.1 to 3 mm. Then, in order to further improve the holding and fixing property, it is desirable to form the inner surface of the molded body 6a into an uneven inner surface.

The first stretching deformation treatment of the molded body 6a is preferably performed so that the length thereof is about 1.5 to 10 times, preferably about 2 to 6 times. Is preferably performed so that its vertical and horizontal dimensions are about 3 to 10 times. The temperature difference between the first deformation treatment temperature (Tf1) and the second deformation treatment temperature (Tf2) needs to be 10 ° C. or higher as in the case of the shape memory material 3 for vascular anastomosis described above. It is desirable to set the temperature difference to -30 ° C.

Shape memory material 6 for tendon junction of this embodiment
Is subjected to the deformation treatment twice as described above, the original rectangular flat shaped compact 6a having a small opening area has a crystallization temperature (Tc) higher than its glass transition temperature (Tg).
By expanding and deforming only once in the vertical and horizontal directions at a deformation processing temperature (Tf) lower than (100 ° C. when there is no crystallization temperature) and cooling, a substantially rectangular tubular shape having an opening area larger than that of the original molded body 6a is obtained. It may be used as a memory material. Even the shape memory material for tendon junction that has just undergone expansion deformation in this way, when reheated to a temperature above the glass transition temperature, contracts in the longitudinal and lateral directions and has the original flat tubular shape with a small opening area 6a
Since the shape is restored, the cut tendons can be firmly held and fixed and joined.

FIG. 11 is an explanatory view of a shape memory material for tendon junction according to still another embodiment of the present invention.

This tendon-joining shape memory material has a large number of V-shaped cut-and-raised parts 61 inwardly on both upper and lower sides of the above-mentioned generally rectangular tubular shape memory material for tendon-joining 6 having a large opening area. Each of the cut-and-raised parts 61 is formed, heated to a glass transition temperature (Tg) or higher to shrink and restore its shape in advance, and cooled and solidified.

In such a shape memory material for tendon joining, when the shape is restored by reheating and the tendon is joined, the cut-and-raised portions 61 that have been contracted and solidified in advance bite into the upper and lower surfaces of the tendon, so that the tendon is There is an advantage that it can be surely prevented from coming out.

The V-shaped cut and raised portion 61 is shown in FIG.
It is preferable to form the tip of the shape memory material 6 so as to face the center of the shape memory material 6, as shown in FIG.

Another constitution of the shape memory material for tendon junction is as follows:
Since it is the same as the shape memory material 6 for tendon junction described above, description thereof will be omitted.

FIG. 12 is an explanatory view of a shape memory biodegradable and absorbable material for suturing (hereinafter referred to as a shape memory material for suturing) according to still another embodiment of the present invention, and FIG. 13 is a description of its usage. It is a figure.

The shape memory material 7 for suturing is made of a dissected ring-shaped lactic acid polymer molding.
It is a material that, when heated above a predetermined temperature (deformation processing temperature (Tf) to be described later), restores its shape to a memorized small-diameter cut ring shape without applying external force.

That is, the shape memory material 7 for suturing has a crystallization temperature (Tc) higher than the glass transition temperature (Tg) of the small-diameter ring-shaped molding 7a made of a lactic acid polymer.
At a deformation treatment temperature (Tf) lower than (100 ° C. when there is no crystallization temperature), the large-diameter ring-shaped compact 7b is subjected to the expansion deformation treatment, and the large-diameter ring-shaped compact 7c is cut out and expanded.
One end of the hook is bent and deformed into a shape that can be engaged with the suture needle to form the hook portion 71, and the glass transition temperature (T
g) The shape is fixed by cooling to a lower temperature.

When the shape memory material 7 for suturing as described above is reheated at a temperature equal to or higher than the deformation processing temperature (Tf), the original small-diameter ring-shaped molded body 7a is restored to the cut shape. Therefore, a suture needle is attached to the hook portion 71 at one end of the shape memory material 7 for suturing, and the incised part 104 of the living body is sewn by the required number of needles as shown in FIG. Temporary suturing is performed by passing through both side edges of the formed portion 104, and when the shape memory material 7 is brought into contact with a heat source such as hot water or hot air having a deformation processing temperature Tf or higher in the state of temporary suturing to reheat, The shape memory material 7 can quickly restore the original small-diameter ring-shaped molded body 7a to the incised shape, close the incision site 104 of the living body, and perform suture easily and reliably.

In order to firmly suture the incision site 104, the inner diameter of the original small-diameter ring-shaped molded body 7a is set to 0.1.
.About.5 mm, outer diameter of 0.3 to 7 mm, length of 0.
It is desirable to set it to about 3 to 5 mm, and it is desirable to perform the expansion deformation processing of this molded body 7a so that the inner diameter of the molded body 7a becomes a large diameter ring shaped molded body 7b. Needless to say, the ring shape may be various ring shapes such as an elliptical shape, a polygonal shape of a triangle or more, and an irregular shape, in addition to the perfect circular shape as in this embodiment. If the original shape of the molded body 7a is set such that both cut ends of the cut small-diameter ring are overlapped with each other, the cut site 104 is more firmly fixed when the shape is restored by reheating. It is desirable because it has the advantage of suturing.

In this embodiment, the hook portion 71 is formed by further bending and deforming one end of the incised large-diameter ring-shaped formed body 7c, but the small-diameter ring-shaped formed body 7a is formed.
Is expanded and deformed into a large-diameter ring-shaped molded body 7b at the above deformation processing temperature (Tf), cooled to a temperature lower than the glass transition temperature (Tg) to fix the shape, and this is molded body 7c. Alternatively, the shape memory material for suturing may be formed by incising.

FIG. 14 is an explanatory view of a shape memory material for suturing according to still another embodiment of the present invention. The shape memory material for suturing 70 is a thread-shaped molded body of lactic acid-based polymer and has a predetermined temperature. When heated above the (deformation processing temperature (Tf) to be described later), the thick yarn shape is shortened and restored without applying an external force.

That is, for the shape memory material 70 for suturing, for example, a lactic acid-based polymer is melt-extruded to form a thick thread-shaped molded body 70a, and the molded body 70a is crystallized at a temperature higher than the glass transition temperature (Tg). At a temperature (Tf) lower than (Tc) (100 ° C. when there is no crystallization temperature), the yarn is stretched and deformed into a thread shape thinner and longer than the above thread shape, and cooled to a temperature lower than the glass transition temperature (Tg) as it is. Then, the thin thread shape is fixed.

Such a thread-shaped shape memory material for suture 7
0 is used for suturing an incised part of a living body like a conventional suture, but it does not need to be tightly tied like a conventional suture, and temporarily sutured in a loosely tied state, and the glass transition temperature (T
g) By simply contacting with a heat source such as warm air or warm water (sterilized physiological saline) and reheating, the material 70 is instantly shortened and restored to the original thick thread shape, and the suture is tightly bound. As a result, the labor required for suturing can be significantly reduced.

The thickness of the original thread-shaped molded body 70a is 0.2.
It is appropriate to set the thickness to about 1 mm, and if the thickness is about this, the tensile strength is sufficient, so that the concern of cutting is eliminated. Further, the stretching deformation treatment of the molded body 70a has a stretching ratio of 1.5 to 10 times, preferably 2 to 6 times.
It is desirable to do so as to double.

In this embodiment, both the original molded body 70a and the shape memory material for suturing 70 have a thread shape with a perfect circular cross section, but they may have a thread shape with an elliptical or rectangular cross section. . When obtaining a thread-shaped shape memory material for suturing having a rectangular cross section, the thickness of the molded article having the original rectangular cross section is set to about 0.2 to 0.4 mm and the width is set to about 0.5 to 1.5 mm. It is appropriate to do.

FIG. 15 is an explanatory view of a shape memory biodegradable and resorbable material for osteosynthesis (hereinafter referred to as a shape memory material for osteosynthesis) according to still another embodiment of the present invention, and FIG. 16 is a compression deformation process. And FIG. 17 are explanatory views of a method of using the shape memory material for osteosynthesis.

The bone-bonding shape memory material 8 is made of a rod-shaped molded body of lactic acid-based polymer, and its shape does not apply an external force when heated to a temperature higher than a predetermined temperature (deformation processing temperature (Tf) described later). However, it is a material that is restored to a memorized bar shape that is thicker and shorter than the above bar shape.

That is, in the shape memory material 8 for bone bonding, the thick round bar shaped body 8a made of lactic acid-based polymer has a crystallization temperature (Tc) higher than its glass transition temperature (Tg).
At a deformation treatment temperature (Tf) lower than (100 ° C. when there is no crystallization temperature), a compression deformation treatment is performed on a round bar-shaped molded body that is longer and thinner than the above-mentioned molded body, and is lower than the glass transition temperature (Tg) as it is. The thin round bar shape is fixed by cooling to temperature.

When the shape memory material 8 for osteosynthesis is reheated to a temperature equal to or higher than the deformation treatment temperature (Tf), the shape is instantly restored to the original thick round bar shaped body 8a. Therefore, as shown in FIG. 17, the shape memory material 8 for osteosynthesis is used as a substitute for a conventional intramedullary nail, and the shape memory material 8 is halved in the medullary canals 106a, 106a of the fractured or cut bone 106. Insert one by one, and the deformation processing temperature (T
f) When the above warm water (sterilized physiological saline) or the like is contacted and reheated, the shape memory material 8 for osteosynthesis restores its shape to the original thick round bar shaped body 8a and the medullary canals 106a, 10a.
The bones 106 and 106 can be easily and surely joined because they are closely attached to the inner surface of 6a and are fixed so as not to be extracted.

Further, the shape-memory material 8 for osteosynthesis is used as a substitute for a conventional osteosynthesis pin, and a hole having a slightly larger diameter is made in a bone piece to be joined by a drill etc. It is also possible to insert the memory material 8 into the hole and similarly reheat it to restore its shape to join the bone fragments.

The original thick round bar shaped body 8a may be molded by various molding means such as melt extrusion molding, injection molding, pressure (press) molding, and its size is the same as that of conventional intramedullary nails and bone joints. It may be almost the same as the pin.

As the means for compressing and deforming the original molded body 8a,
For example, the means as shown in FIG. 16 is preferably adopted. That is, the compression deformation means includes a large-diameter cylindrical storage cavity 105a having a large cross-sectional opening area and a small-diameter cylindrical bottomed molding cavity 105c having a small cross-sectional opening area.
Between the inner peripheral surface and the tapered portion 105b whose inner peripheral surface is a tapered surface is coaxially provided, the molded body 8a is housed in the housing cavity 105a, and A thin round bar shape is obtained by continuously or intermittently press-fitting the molded body 8a into the molding cavity 105c at the above-mentioned deformation processing temperature (Tf) by the male shape 105d for pressure, and then cooling it to fix the shape. The memory material 8 is obtained.

In that case, the ratio of the opening area of the housing cavity 105a and the molding cavity 105c is set within the range of 1.5 to 6.0, and the deformation ratio (cross-sectional area of the molded body 8a / cross-sectional area of the shape memory material 8) is set. ) Is preferably adjusted to be substantially in the range of 1.5 to 6.0. This is because if the deformation ratio is less than 1.5, the effect of shape restoration becomes insufficient, and if it exceeds 6.0, there arises such a disadvantage that the material becomes inhomogeneous such as porosity or fibrillation.

It is also a useful method to incorporate the bioactive bioceramic powder in the range of 10 to 60% by weight, preferably 20 to 50% by weight in the shape memory material 8 for bone bonding. When the shape-memory material 8 for osteosynthesis containing the bioceramics powder is inserted into the medullary hole or the hole drilled as described above, the shape-recovering material adheres well to the surrounding tissue. The bone tissue is reliably reproduced on the surface layer of the material 8 by the bioceramic powder exposed on the surface of the material 8 and the bioceramic powder exposed by the hydrolysis of the lactic acid-based polymer of the material 8 from the surface. The material 8 has an advantage that it is formed by induction, and the material 8 is fixed by being combined with living bone in a short period of time.

As the bioceramic powder, the above-mentioned powders are used. Among them, wet hydroxyapatite, tricalcium phosphate powder and the like, which have a high ability to induce and form bone tissue and have been widely used, are particularly useful. .

In this embodiment, the original molded body 8a
Although the shape memory material 8 for bone attachment is also a round bar shape, for example, when it is used as a substitute for an intramedullary nail, it may be a square bar shape.
Alternatively, a deformed body having an appropriately curved shape may be used. In short, as long as it is solid and has a long rod shape, it may have any cross-sectional shape and may be curved.

FIG. 18 is an explanatory view of a shape memory biodegradable and absorbable material for fixing an osteosynthesis plate (hereinafter, referred to as a shape memory material for fixing an osteosynthesis plate) according to still another embodiment of the present invention. Is an explanatory view of a method of using the same.

Shape memory material 9 for fixing the bone joint plate
Is obtained by cutting the above-described round bar-shaped shape memory material 8 for bone attachment and processing it into a tapered pin having a diameter of one end surface smaller than the diameter of the other end surface. When this is reheated to a temperature above the deformation treatment temperature (Tf), it expands in the radial direction while contracting in the lengthwise direction, as shown by the chain line, and it has a large diameter and a short length. The shape is restored to.

The tapered pin-shaped shape memory material 9 can be used as it is as a bone-joining pin, and as shown in FIG.
It is preferably used for fixing 07.

That is, a plurality of holes 106b having a diameter slightly larger than the diameter of the shape memory material 9 are bored in the bone 106, and the tapered pin-shaped shape memory material 9 is inserted in each hole 106b toward the other end surface having a larger diameter. Insert from. Then, the bone joint plate 107 having the same number of holes 107a as the holes 106b is placed, and the upper end of the shape memory material 9 protruding from the surface of the bone 106 is passed through each hole 107a of the bone joint plate 107. The osteosynthesis plate 107 is set. Next, a heat source such as hot water (physiological saline) having a deformation processing temperature (Tf) or higher is brought into contact with each shape memory material 9 to restore its shape, and the bone 106 and the bone joint plate 107 are restored.
When the shape memory material 9 is brought into close contact with the respective holes 106b and 107a of the
Fix on the surface of 6. And iron 1 which had been preheated
08 is brought into contact with the upper end surface of each shape memory material 9 protruding from the surface of the osteosynthesis plate 107, and is crimped so that the upper end surface is flush with the surface of the osteosynthesis plate 107. Firmly fix. It should be noted that a method of storing the shape of the upper end of the pin in advance so that the plate 107 can be fixed is also an effective method, instead of the treatment of the upper end of the pin by the heat iron.

It is more effective if the shape memory material 9 for fixing the bone-bonding plate is made to contain the above-mentioned bioceramic powder so that it can be bonded to the bone 106 in a short period of time.

FIG. 20 is an explanatory diagram of a shape memory material for osteosynthesis according to still another embodiment of the present invention, and FIG. 21 is an explanatory diagram of its usage.

This bone-shape shape memory material 10 has two or more pieces (eight pieces in this embodiment) from the peripheral edges of both end surfaces of the columnar portion 10a by cutting the cylindrical molding block 10d made of a lactic acid-based polymer. A molded body 10c having a shape in which an arm portion 10b of the above is inclined and projected to the outside is manufactured, and this molded body 10c is crystallized at a temperature higher than the glass transition temperature (Tg) (Tc) (or 100 if there is no crystallization temperature). ℃)
At a lower deformation processing temperature (Tf), bending processing is performed inward at the base of each arm 10b so that each arm 10b is parallel to the axial direction of the column 10a, and the temperature is lower than the glass transition temperature as it is. It is cooled to fix its shape.

The shape memory material 10 for osteosynthesis as described above is
When reheated to the deformation processing temperature (Tf) or higher, the original molded body 10c in which each arm portion 10b is inclined and opened outward
The shape is restored to.

Therefore, the shape-memory material 10 for bone joining is used for a similar application such as a substitute of a conventional Herbert screw, and as shown in FIG.
When the shape memory material 10 is inserted into the holes 106c, 106c formed in the surfaces to be joined of 106 and heated with warm water (physiological saline) or the like above the deformation treatment temperature (Tf), the shape memory material 10 is formed. Is opened so that the shape is restored to the original molded body 10c and the arm portions 10b are inclined outward, and the tips of the arm portions 10b are pressed into contact with the inner surfaces of the holes 106c and 106c to be fixed. The bones 106, 106 can be easily joined.

The shape memory material 10 for osteosynthesis shown in FIG.
As shown in FIG. 0, it is desirable to form a claw piece at the tip of each arm portion 10b so as to project outward. When such a claw piece is formed, when the shape is restored, the hole 1 described above is formed.
There is an advantage that the inner surface of 06c and the claw piece can be easily caught, and the bones 106 can be joined more firmly.

The shape memory material 10 for osteosynthesis also contains the above-mentioned bioceramic powder,
It is desirable to be able to bond with the bone 106 in a short period of time.

FIG. 22 shows a shape memory biodegradable and absorbable material (hereinafter referred to as bone cement outflow prevention) for preventing outflow of bone cement or bone debris in the medullary cavity according to still another embodiment of the present invention. 23 is a shape memory material for use in manufacturing)
Is an explanatory view of a method of using the same.

This bone cement outflow-preventing shape memory material 11 is formed by cutting a cylindrical molding block 11d made of a lactic acid-based polymer to cut the cylindrical plug portion 11a having a hemispherical lower surface from the peripheral edge of the upper surface of the cylindrical plug section 11a. The above-mentioned (four in this embodiment) petal-shaped projections 11b are formed into a shape in which the petals 11b are inclined and protruded to the outside, and the shaped body 11c is produced. At a deformation processing temperature (Tf) lower than Tc (100 ° C. when there is no crystallization temperature), each petal-shaped protrusion 11b is arranged such that each petal-shaped protrusion 11b is parallel to the axial direction of the cylindrical plug 11a. The shape is fixed by bending and deforming the inner part at the root part and cooling it to a temperature lower than the glass transition temperature.

When the shape memory material 11 is reheated to a temperature higher than the deformation treatment temperature (Tf), the shape of the petaloid projections 11b is quickly restored to the original molded body 11c which is opened by inclining outward. Therefore, as shown in FIG. 23, the bone cement outflow-preventing shape memory material 11 is inserted into the medullary cavity 106a of the bone 106, and hot water (physiological saline) having a temperature higher than the deformation treatment temperature (Tf) is brought into contact therewith to reheat the same. Then, the shape-memory material 11 restores its shape to the original molded body 10c and opens so that each petal-shaped protrusion 11b is inclined outward, and the tip of each petal-shaped protrusion 11b is located on the inner surface of the medullary cavity 106a. It is pressed and fixed.

When the shape memory material 11 is restored and fixed in the medullary canal 106a in this way, and the bone cement 108 is filled from one end (upper end) of the medullary canal 106a, the bone cement 108 is marrowed by each petaloid protrusion 11b. Cavity 106a
It is prevented from flowing out to the lower part of. Therefore, when a stem (not shown) of an artificial joint is inserted into the medullary cavity 106a filled with this bone cement 108, the bone cement 108
With this, the stem can be securely fixed.

This bone cement outflow-preventing shape memory material 11 also preferably contains the above-mentioned bioceramic powder so that it can be bonded to the bone 106 in a short period of time. It is desirable to form a claw piece that projects outward at the tip to improve the catching with the inner surface of the medullary cavity 106a.

The dimensions of each part of the original molded body 11c may be appropriately set according to the size of the medullary cavity to be inserted.

FIG. 24 is an explanatory view of a shape memory biodegradable and absorbable material for preventing vascular restenosis (hereinafter, referred to as a shape memory material for preventing vascular restenosis) according to still another embodiment of the present invention.
FIG. 25 is an explanatory diagram of how to use it. The shape memory material 12 for preventing vascular restenosis is a molded body 12a made of a perforated cylindrical lactic acid-based polymer in which a large number of holes 12b are formed.
At a deformation treatment temperature (Tf) higher than its glass transition temperature (Tg) and lower than its crystallization temperature (Tc) (100 ° C when there is no crystallization temperature), it is flatly folded and rolled into a cylindrical shape. It is bent and deformed and then cooled to a temperature lower than the glass transition temperature to fix its shape.

When the shape memory material 12 is reheated to the deformation processing temperature (Tf) or higher, the shape of the shape memory material 12 is restored to the original shape of the perforated cylindrical shaped body 12a. Therefore, this shape memory material 12 for preventing vascular restenosis is used as a substitute for a conventional stent for preventing restenosis, and the shape memory material 12 is inserted into a blood vessel 110 such as a coronary artery as shown in FIG. When hot water (physiological saline) having a deformation temperature (Tf) or higher is contacted and reheated, the shape memory material 12 is restored to the original cylindrical shaped body 12a, and the blood vessel 110 is expanded and expanded again from the inside. Stenosis can be prevented.

This shape-memory material 12 for preventing vascular restenosis contains a restenosis-preventing drug, and when fixed in the blood vessel 110 as described above, the restenosis-preventing drug is released from the shape-memory material 12 at a constant rate. Can be devised to be done.
When the drug is contained in this way, if the original molded product 12a having a perforated cylindrical shape is produced by means such as melt extrusion molding, there is a possibility that the drug will deteriorate due to a high molding temperature. In order not to do so, it is desirable to manufacture the original perforated cylindrical molded body 12a by the following method.

That is, a lactic acid-based polymer and a drug are dissolved in a solvent to prepare a polymer solution, which is sprayed onto the core rod 109 to volatilize the solvent, thereby forming a thick cylindrical film around the core rod 109. After forming a large number of holes 12b in this cylindrical film, the core rod 109 is extracted to obtain a cylindrical formed body 12a.

In this case, a mixed solvent of a solvent capable of dissolving the lactic acid type polymer and a non-solvent having a boiling point higher than this solvent is used to dissolve the lactic acid type polymer and the drug to prepare a polymer solution. In the same manner as above, a perforated cylindrical foamed molded product having open cells can be obtained. The shape-memory material for vascular restenosis, which is obtained by bending and deforming such a perforated cylindrical foamed molded product, has a much larger surface area than a non-foamed product when the shape is restored and fixed in the blood vessel. There are advantages that the progress of decomposition is fast and the amount of drug released is large.

The shape memory material 12 for preventing vascular restenosis of this embodiment is obtained by subjecting the original molded body 12a having a perforated cylindrical shape to bending deformation processing into a folded cylindrical shape.
An original molded body having a mesh-like cylindrical shape with a mesh may be produced and similarly subjected to bending deformation treatment. Alternatively, an original molded body having a large-diameter coil (helix) shape may be produced, and this may be subjected to reduction (pulling) deformation processing into a small-diameter coil (helix) shape to obtain a shape memory material for preventing vascular restenosis.

Although some specific uses have been described above, there are many uses other than these, and it goes without saying that all of them are included in the present invention without departing from the scope of the present invention. Nor.

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

[Example 1] Viscosity average molecular weight obtained by ring-opening polymerization of DL-lactide 400,000, 250,000, 150,000, 10
10,000 and 70,000 poly-D, L-lactic acid (PDLLA) were respectively pressure-molded at 160 ° C. and 100 kg / cm ² to form round bar-shaped PDLLA having a diameter of 10.0 mm and a length of 20 mm. Five compacts were obtained. The glass transition temperatures of these molded bodies were all in the range of 50 to 56 ° C.

Next, these molded bodies were heated to 60 ° C. and subjected to compression plastic deformation treatment so as to form elongated round bar-shaped molded bodies having a diameter of 5.8 mm and a length of 60 mm, respectively.
By cooling and fixing the shape at room temperature, five shape memory biodegradable and absorbable materials having the original round bar shape memorized were obtained. Assuming that the cross-sectional area of these shape memory materials is S ₁ , the length is L ₁ , the cross-sectional area of the original molded body before plastic deformation is S ₀ , and the length is L ₀ , any shape memory material is cut. Deformation of area R _S = S
₀ / S ₁ = 3.0, degree of deformation of length R _L = L ₀ / L ₁ =
It is 3.0.

Next, these shape memory materials were immersed in physiological saline at 65 ° C. to recover the shape, and the cross-sectional area S ₂ and length L ₂ after the recovery were measured, and the recovery rate of the cross-sectional area [( S ₂
/ S ₀ ) × 100] (%) and the length recovery rate [(L ₂ /
L ₀ ) × 100] (%) was determined. The results are shown in Table 1.

[Table 1]

The shape of each shape memory material is 65 ° C.
After being dipped in the physiological saline solution, it recovered instantly. It can be confirmed that the shape memory materials of any molecular weight have a high cross-sectional area recovery rate and length recovery rate of 96.7% or more, and almost completely recover the original round bar shape before deformation. It was

The shape recovery rate was somewhat dependent on the molecular weight of the shape memory material. It is considered that this is because as the molecular weight becomes higher, the fluidity of PDLLA becomes worse, and internal strain occurs during plastic deformation of the original molded body, and the shape is memorized. However, in essence, it seems that the original round bar shape is completely restored.

PDL obtained by ring-opening polymerization of DL-lactide
Since LA is generally an amorphous polymer, it is well known that hydrolysis after implantation in a living body is faster than that of poly-L-lactic acid (PLLA) which is a crystalline polymer. Further, the strength of the molded product is lower than that of a high strength product in which molecular chains (crystal axes) are oriented by a treatment such as orientation of PLLA. PDLLA may cause an orientation of an amorphous phase and a partial crystalline phase due to a treatment such as orientation, which results in some strength improvement. that is,
It depends on the difference in the lactide ratio between the D-form and the L-form (whichever is higher), the selection of the type of copolymer and the conversion of the monomer ratio at that time, and the magnitude of the molecular weight.

The required strength of the shape memory material, its maintenance period, the speed of absorption, and the like can be adjusted by converting these factors. Further, the decomposition rate can also be adjusted by adjusting the content of the lactide monomer contained in the polymer.

Example 2 Three kinds of PDLLA having a viscosity average molecular weight of 150,000, obtained by polymerizing D-lactide and L-lactide in a weight ratio of 25:75, 40:60 and 50:50.
Were respectively pressure-molded at 160 ° C. and 100 kg / cm ² to obtain three round bar-shaped molded bodies having a diameter of 10 mm and a length of 10 mm. The glass transition temperatures of these molded bodies were all in the range of 50 to 60 ° C.

Next, these compacts were heated to 65 ° C., respectively subjected to compression plastic deformation treatment so as to obtain elongated slender rod-shaped compacts having a diameter of 5 mm and a length of 40 mm, and then cooled to fix the shape at room temperature. Then, three shape memory materials having a deformation degree R _S = R _L = 4.0 in which the original round bar shape was memorized were obtained.

These shape memory materials were immersed in a physiological saline solution having a temperature higher than that of Example 1 at 70 ° C., and the shape recovery rate (recovery rate of cross-sectional area and recovery rate of length) of each was measured. The measurement results are shown in Table 2.

[Table 2]

The shape of each shape memory material is 70 ° C.
After being dipped in the physiological saline solution, it recovered instantly. The size of the shape recovery rate depends on the ratio of D-lactide and L-lactide at the time of polymerization, and when the ratio is equal, the value of the shape recovery rate increases, and it tends to easily recover to the state before plastic deformation. Became. PDLLA, which has a high proportion of either D-lactide or L-lactide, has a hydrogen bond in the molecular chain because a chain portion in which L-lactic acid or D-lactic acid is continuous is present in the polymer molecular chain. It is considered that one of the reasons is that the recovery rate at 70 ° C. was slightly small because the crystallization occurred slightly and the crystallization occurred slightly.

[Example 3] D having a viscosity average molecular weight of 200,000,
L-lactic acid-glycolic acid copolymer (D, L-lactic acid: glycolic acid = 97.5: 2.5) at 180 ° C., 100 kg
/ Cm ² pressure molding, diameter 13.0mm, length 30
A round bar-shaped molded body of mm was obtained. The glass transition temperature of this molded product was 51 ° C.

Next, this molded body was heated to 65 ° C., subjected to compression plastic deformation treatment so as to obtain a molded body having an elongated round bar shape having a diameter of 7.5 mm and a length of 90 mm, and then cooled to fix the shape. , Deformation degree R _S = _RL that remembers the original round bar shape
= 3.0 of the shape memory material was obtained.

Then, this shape memory material was immersed in a physiological saline solution at 67 ° C., and its shape recovery rate (recovery rate of cross-sectional area and recovery rate of length) was measured. The results are shown in Table 3.

[Table 3]

The shape of this shape memory material was recovered instantly after being immersed in a physiological saline solution at 67 ° C. The recovery rate of its cross-sectional area and the recovery rate of its length were 98% or more, and it was possible to almost completely restore the original round bar shape before plastic deformation.

[Example 4] PL having a viscosity average molecular weight of 100,000
Granules obtained by mixing LA and PDLLA having a viscosity average molecular weight of 100,000 obtained by ring-opening polymerization of D, L-lactide in a weight ratio of 70:30 were prepared at 185 ° C. and 100 kg / cm.
^By pressure molding in ² , a round bar shaped body having a diameter of 10 mm and a length of 20 mm was obtained. The apparent glass transition temperature of this molded product was around 60 ° C.

Next, this molded body was heated to 85 ° C., subjected to compression plastic deformation treatment so as to form a slender round bar-shaped molded body having a diameter of 6.3 mm and a length of 50 mm, and then cooled to fix the shape. Deformation degree R _S = _RL = where the original round bar shape is memorized
A shape memory material of 2.5 was obtained.

This shape memory material was immersed in physiological saline at 85 ° C., and its shape recovery rate (recovery rate of cross-sectional area and recovery rate of length) was measured. The measurement results are shown in Table 4.

[Table 4]

The shape of this shape memory material was instantly recovered after immersion in 85 ° C. physiological saline. The shape recovery rate was slightly lower than that of the shape memory material of PDLLA having a viscosity average molecular weight of 100,000 of Example 1, but the shape was restored to a round bar shape before plastic deformation. The reason for the decrease was PL of shape memory material
Due to the orientation of the LA part due to the plastic deformation of the secondary shaping,
It is thought that this was due to slight crystallization.

[Example 5] Viscosity average molecular weight 1 obtained by polymerizing D-lactide and L-lactide in a weight ratio of 50:50.
50,000 PDLLA (used in Example 2) was dissolved in dichloromethane, unbaked hydroxyapatite (u-HA) was added to this solution, and then ethyl alcohol was added with stirring to add PDLLA and u-HA. Was co-precipitated.
It was then filtered and dried completely to give u-HA 4
Two types of PDLLA granules were obtained which were uniformly dispersed at a ratio of 0% by weight and 50% by weight.

Each of these granules was pressure-molded under the same conditions as in Example 2 to obtain two types of round bar-shaped compacts having a diameter of 10 mm and a length of 10 mm. Then, these molded bodies are heated to 70 ° C. to have a diameter of 6.0 mm and a length of 28 mm.
Elongated bar shape (deformation degree R _S = R _L = 2.
After compression plastic deformation treatment in 8), cooling and fixing the shape, this molded body is further cut to have a diameter of 1.2 mm on one end surface, a diameter of 1.5 mm on the other end surface, and a length of 25 m.
Two types of tapered shape memory pins (memory shape material) of m were manufactured. Then, these tapered shape memory pins are immersed in a physiological saline solution at 70 ° C., and the shape recovery rate (recovery rate of cross-sectional area of one end surface, recovery rate of cross-sectional area of other end surface, length recovery rate). Was measured. The results are shown in Table 5.

[Table 5]

The shape of each tapered shape memory pin was instantaneously restored to a thick and short tapered pin shape after being immersed in saline at 70 ° C., and the recovery rate of the cross-sectional area of one end surface of the pin, etc. The recovery rate of the cross-sectional area of the end face and the recovery rate of the length were both high at about 93% or more. From this example, it can be seen that a shape memory material of a composite of bioceramic powder and PDLLA can be obtained.

Next, of the above-mentioned tapered shape memory pins, an attempt was made to use a pin made of a composite of u-HA / PDLLA = 50/50 (wt%) as a plate fixing pin for osteosynthesis. It was

As shown in FIG. 19, first, the femur 1 of the rabbit
Holes 106b having a diameter of 2.0 mm are drilled at 6 points on a straight line at a distance of 5 mm in 06, and u-HA / PDLLA = 50.
The tapered shape memory pin 9 made of a composite of 50/50 (% by weight) is provided in each hole 106b from the other end face having a large diameter.
Inserted in. Next, HA / PDLLA = 50/5, in which holes having a diameter of 2.2 mm were perforated at 4 positions on a straight line at intervals of 5 mm.
Plate 10 for osteosynthesis consisting of 0 (wt%) composite
7 on the femur 106, and the other end (upper end) of the tapered shape memory pin 9 protruding from the surface of the femur 106
Through the holes 107a of the plate 107
7 was installed. Then, physiological saline at 70 ° C. was poured onto the tapered shape memory pin 9 to recover the shape of the pin 9, thereby fixing the plate 107 to the surface of the femur 106. Further, the trowel 108 that has been heated to 150 ° C. in advance is brought into contact with the upper end of the pin 9 protruding from the surface of the plate 107, and crimped so that the upper end of the pin is flush with the surface of the plate 107, The plate 107 was firmly fixed.

Next, a pull-out test of the plate fixed to the femur was conducted. First, the femur with the plate fixed was installed in a universal testing machine, and the fixed plate was sandwiched by a special jig to apply stress in the direction of pulling out the plate. As a result, the plate did not separate from the pin, and the plate was broken.

From the above, it was proved that this tapered shape memory pin can easily and surely fix the bone-bonding plate to the living bone, so that the conventional screw can be used to fix the plate to the fractured part. Compared with the fixed bone joining method, a much easier bone joining method has become possible.

Example 6 The PDLLA having a viscosity average molecular weight of 250,000 used in Example 1 was used at 160 ° C. and 100 kg / cm.
^By pressure molding in ² , a round bar shaped body having a diameter of 15 mm and a length of 50 mm was obtained. Then, this molded body was cut to produce a molded body 11c having a shape in which four petal-shaped protrusions 11b were inclined and protruded outward from the peripheral edge of the upper surface of the cylindrical plug portion 11a as shown in FIG. .

The molded body 11c was dipped in a physiological saline solution at 60 ° C., and the roots of the petal-shaped projections 11b were placed inward so that the petal-shaped projections 11b were parallel to the axial direction of the plug 11a. A shape memory material 11 for preventing bone cement outflow which memorized the shape of the original molded body 11c was obtained by bending and deforming the petaloid protrusions 11b to form a closed shape and then cooling and fixing the shape. .

This shape memory material 11 was inserted into the medullary cavity of the rabbit femur, and physiological saline at 60 ° C. was poured onto the shape memory material 11. Each petal-shaped protrusion 11 of the shape memory material 11
b was restored to its original open shape, and the shape memory material 11 was fixed in the medullary cavity.

Next, bone cement was injected into the medullary canal with the plug facing down and the cement on top, and after hardening, the femur was split lengthwise to prevent leakage of bone cement in the medullary canal. It was confirmed whether or not it was taken out. As a result, it was confirmed that the bone cement was hardened in the medullary cavity above the shape memory material 11 and did not leak into the lower medullary cavity.
The inserted bone cement outflow-preventing shape memory material 11 was firmly fixed in the medullary cavity.

Example 7 A copolymer having a viscosity average molecular weight of 150,000, obtained by polymerizing L-lactide and D, L-lactide in a weight ratio of 95: 5, was used to prepare hydroxyapatite in the same manner as in Example 6. Coprecipitated with (HA) and dried to obtain copolymer granules in which u-HA was uniformly dispersed at a ratio of 40% by weight.

This was pressure-molded at 185 ° C. and 100 kg / cm ² to obtain a round bar-shaped molded body having a diameter of 10 mm and a length of 40 mm. The apparent glass transition temperature of this molded product was 62 ° C.

Next, this molded body was cut to obtain the shape shown in FIG.
Molded body 10c having a shape shown in 0 (L: 35 mm, d: 3 m
m, D: 5 mm) was produced. And this molded body 10
c is heated to 85 ° C. so that each arm portion 10b becomes a cylindrical portion 10.
Bending deformation processing was performed inward at the root portion of each arm portion 10b so as to be parallel to the axial direction of a, and the shape memory material 10 for osteosynthesis in which the shape of the original molded body 10c was stored was obtained.

Next, the tibia of the rabbit was cut in the middle to obtain two bone fragments. Then, a hole having a diameter of 4 mm and a depth of 18 mm is made in each of the cut surfaces of these bone pieces, the shape memory material 10 for osteosynthesis is inserted thereinto to join the two bone pieces, and then a physiological saline solution of 85 ° C. Was poured to restore the shape of the shape-memory material 10 for bone bonding, and both bone fragments were firmly bonded and fixed. A stress in the pulling direction was applied to the bonded and fixed bone fragments, but the bone fragments were firmly bonded and the bone-bonding shape memory material 10 did not come out from the holes of the bone fragments.

From this, it was demonstrated that the above-described shape-memory material 10 for osteosynthesis can sufficiently fix bone fragments.

Example 8 Poly-DL-lactic acid (glass transition temperature: 51 ° C.) having a viscosity average molecular weight of 100,000 obtained by ring-opening polymerization of DL-lactide (180 ° C., inner diameter 1 mm, outer diameter 5 m).
A small-diameter ring-shaped molded body having an inner diameter of 1 mm, an outer diameter of 5 mm, and a length (width) of 2 mm was obtained by extrusion molding into a small-diameter cylindrical shape of m, cooling and cutting. Then, this small-diameter ring-shaped molded body was subjected to an atmosphere of 60 ° C. and an inner diameter of 10 mm and an outer diameter of
After being expanded and deformed into a large-diameter ring shape having a length of 5 mm and a length (width) of 1.5 mm, the shape was fixed by cooling to produce a shape memory material in which the original small-diameter ring shape was memorized.

When this shape memory material was immersed in hot water at 70 ° C., the inner diameter, outer diameter and length (width) were instantly restored to almost the same shape as the original small diameter ring.

Example 9 Poly-DL-lactic acid having a viscosity average molecular weight of 70,000 (glass transition temperature: 50 ° C.) obtained by ring-opening polymerization of DL-lactide at 180 ° C. has an inner diameter of 0.5 mm and an outer diameter of 3. Extruded into a small cylindrical shape with a diameter of 2 mm, cooled and then cut to an inner diameter of 0.5 mm, an outer diameter of 3.2 mm, and a length (width).
A ring-shaped compact having a diameter of 1.0 mm was obtained. This small-diameter ring-shaped molded body has an inner diameter of 5.0 m in an atmosphere of 55 ° C.
m, outer diameter 6.1 mm, length (width) 0.8 mm, expanded and deformed into a large-diameter ring shape, and then cooled to fix the shape, and the original small-diameter ring shape was memorized. Material) was prepared.

After this blood vessel ligation ring was inserted into the end of the cut blood vessel (thickness: about 1 mm) in the abdomen of the rabbit, 6
The physiological saline of 0 degreeC was sprayed. Then, the blood vessel ligation ring was instantly restored to its original small-diameter ring shape, and the blood vessel was ligated, and hemostasis could be completely stopped. To be on the safe side,
The shape-recovered ring was flatly crimped with pliers heated to 80 ° C. to completely seal the blood vessel. Then, 12 weeks later, the rabbit was slaughtered and the blood vessel was examined. As a result, the ring was almost disappeared, but the blood vessel was occluded and hemostasis was continued.

Example 10 Poly-D, L-lactic acid having a viscosity average molecular weight of 150,000 (glass transition temperature: 52) obtained by polymerizing D-lactide and L-lactide in a weight ratio of 50:50.
(° C) is extruded at 180 ° C into a small-diameter cylindrical shape having an inner diameter of 3 mm and an outer diameter of 5 mm, cooled and then cut to have an inner diameter of 3 mm,
A small-diameter ring-shaped molded product having an outer diameter of 5 mm and a length (width) of 1 mm was obtained. This small-diameter ring-shaped molded body was subjected to an atmosphere of 60 ° C., an inner diameter of 15 mm, an outer diameter of 15.7 mm, and a length (width).
The shape is fixed by expanding and deforming into a 0.7 mm large-diameter ring shape, incising it, and bending and cooling one end into a hook shape that can engage with the suture needle, and fixing the shape, as shown in FIG. A shape memory material for suture 7 having a simple hook portion 71 was produced.

A suture needle is engaged with the hook portion 71 at one end of the shape memory material 7 for suturing, and several incised portions of the abdomen of the rabbit are sewn, and as shown in FIG.
Several incision sites 104 were sewn together with. Then, when 65 ° C. physiological saline is sprayed on each of the suture shape memory materials 7, each suture shape memory material 7 instantly restores the original small-diameter ring-shaped molded body to the incised shape, and the incision site 10 is formed.
4 could be firmly sutured.

Example 11 A solution of poly-D, L-lactic acid (glass transition temperature: 54 ° C.) having a viscosity average molecular weight of 250,000 (glass transition temperature: 54 ° C.) obtained by ring-opening polymerization of DL-lactide was dissolved in dichloromethane. 5 mm, width 2 mm, length 50 mm, applied to the periphery of a polyethylene square bar to volatilize dichloromethane to a length of 20 mm, wall thickness 0.75 mm, internal dimension 0.5 mm, width 2 mm flat. A rectangular tubular shaped body was obtained.

This molded body was made to have a length of 40 at 80 ° C.
After being stretched into a flat rectangular tube of mm, cooled, and fixed in shape, the opening area is 40 mm in length, 0.1 mm in wall thickness, 5 mm in length, and 10 mm in width in an atmosphere of 60 ° C. By expanding and deforming it into a flat rectangular tube-shaped molded body having a large size, cooling and fixing the shape, a shape memory material for tendon junction in which the original rectangular tube shape was memorized was produced.

When the cut ends of the tendon of the cut rabbit foot were inserted into both ends of this shape memory material from both sides and physiological saline at 60 ° C. was sprayed on the shape memory material, the internal dimensions of the shape memory material were instantaneously changed. By contracting into a rectangular tube shape with a small opening area of 0.5 mm in length and 2 mm in width and tightly holding and holding the cut end of the tendon from the surroundings, and further spraying a physiological saline solution at 80 ° C. It was possible to restore the original short tubular shape of 20 mm and join the cut ends of the tendon in a state of being pulled together.

[Example 12] 100 parts by weight of poly-D, L-lactic acid (glass transition temperature: 50 ° C) having a viscosity average molecular weight of 70,000 obtained by ring-opening polymerization of DL-lactide, and an agent for preventing restenosis of blood vessels. 150 parts by weight of tranilast was dissolved in chloroform to prepare a solution having a solid content of 3% by weight, which had a diameter of 5.
8.0 kgf / cm ² on a 0 mm polyethylene round bar
It was sprayed at a discharge pressure of 1 to volatilize chloroform to produce a cylindrical membrane having a thickness of 0.3 mm. And this cylindrical membrane 1
Cut to a length of 5 mm and have a diameter of 1.5 m around the cylindrical membrane.
After forming a large number of m holes, the round bar was pulled out to obtain a perforated cylindrical molded body 12a as shown in FIG. This product has a total weight of 36 mg and the encapsulated drug weighs 21.
It was 6 mg.

In the atmosphere of 55 ° C., this molded product having a perforated cylindrical shape was bent and deformed into a cylindrical shape (outer diameter of about 1.0 mm) which was flatly folded, rolled up and folded as shown in FIG. By rapidly cooling and fixing the shape, a thin scroll-shaped stent (shape memory material) 12 for preventing the restenosis of the blood vessel having a memory of the original perforated cylindrical shape was obtained.

In order to confirm that this stent remembers the original shape and to measure the drug release rate,
The following tests were performed in vitro.

The stent was inserted into a silicone tube having an inner diameter of 4.0 mm, and warm water at 60 ° C. was introduced. Then, the stent was expanded and restored to its original cylindrical shape as the temperature increased, and it was possible to fix the inner surface of the tube with the inner surface of the tube being lined by the force of pressing the inner wall of the tube. This was immersed in a 0.2 mol phosphate buffer having a pH of 7.4 and adjusted to 37 ° C., and the amount of tranilast released into the buffer along with the decomposition of poly-D, L-lactic acid was periodically measured. .
As a result, as shown in FIG. 26, it was confirmed that the drug was released at a constant rate for 12 weeks, and that 68% of tranilast initially encapsulated was released during this period. It could be confirmed that poly-D, L-lactic acid still slightly remained.

From the above, it was found that this shape memory biodegradable and absorbable stent exhibits excellent performance as a base material for DDS.

[0193]

As is apparent from the above description, the shape memory biodegradable and absorbable material of the present invention is reheated at a temperature not lower than the deformation treatment temperature to ligate (hemostatic) a cut blood vessel or Performing ligation, anastomosis, suturing, joining, restenosis prevention, and other procedures of living tissues such as anastomosis, suturing of incision site, joining of cut tendons, joining of bones, prevention of vascular restenosis, etc. are extremely simple and reliable. Since the temperature of shape recovery is low at the time of reheating, there is no fear of burning the biological tissue, and it does not cause halation phenomenon of MRI or CT, is decomposed and absorbed in the body and remains in the body. There is a remarkable effect that there is no.

Since it contains the bioceramics powder, it can be firmly fixed by being combined with the living bone, and the one containing the drug is devised so as to release the drug at a constant rate. As a result, there is an effect that it can serve as a base material for DDS.

[Brief description of drawings]

FIG. 1 is an explanatory diagram of a shape memory material for blood vessel anastomosis according to an embodiment of the present invention.

FIG. 2 is an explanatory diagram of a method of using the same shape memory material.

FIG. 3 is an explanatory view of a shape memory material for blood vessel anastomosis according to another embodiment of the present invention.

FIG. 4 is an explanatory view of a shape memory material for blood vessel anastomosis according to still another embodiment of the present invention.

FIG. 5 is an explanatory diagram of a method of using the same shape memory material.

FIG. 6 is an explanatory view of a shape memory material for blood vessel ligation according to still another embodiment of the present invention.

FIG. 7 is an explanatory diagram of a method of using the same shape memory material.

FIG. 8 is an explanatory view of a shape memory material for blood vessel ligation according to still another embodiment of the present invention.

FIG. 9 is an explanatory diagram of a shape memory material for tendon junction according to still another embodiment of the present invention.

FIG. 10 is an explanatory diagram of a method of using the same shape memory material.

FIG. 11 is an explanatory view of a shape memory material for tendon junction according to still another embodiment of the present invention.

FIG. 12 is an explanatory diagram of a shape memory material for suturing according to still another embodiment of the present invention.

FIG. 13 is an explanatory diagram of a method of using the same shape memory material.

FIG. 14 is an explanatory view of a shape memory material for suturing according to still another embodiment of the present invention.

FIG. 15 is an explanatory diagram of a shape memory material for osteosynthesis according to still another embodiment of the present invention.

FIG. 16 is an explanatory diagram of a compression deformation process of the same shape memory material.

FIG. 17 is an explanatory diagram of a method of using the same shape memory material.

FIG. 18 is an explanatory view of a shape memory material for fixing an osteosynthesis plate according to still another embodiment of the present invention.

FIG. 19 is an explanatory diagram of a method of using the same shape memory material.

FIG. 20 is an explanatory diagram of a shape memory material for osteosynthesis according to still another embodiment of the present invention.

FIG. 21 is an explanatory diagram of a method of using the same shape memory material.

FIG. 22 is an explanatory diagram of a bone cement blocking shape memory material according to still another embodiment of the present invention.

FIG. 23 is an explanatory diagram of a method of using the same shape memory material.

FIG. 24 is an explanatory diagram of a shape memory material for preventing vascular restenosis according to still another embodiment of the present invention.

FIG. 25 is an explanatory diagram of a method of using the same shape memory material.

FIG. 26 is a graph showing the relationship between the amount of tranilast released and the elapsed time of the shape memory material for preventing vascular restenosis containing tranilast.

[Explanation of symbols]

1, 2 and 3 Shape memory material for blood vessel anastomosis 21a Inner surface with irregularities 4, 5 Shape memory material for blood vessel ligation 6 Shape memory material for tendon junction 61 Cut and raised portion 7,70 Shape memory material for suture 71 Hook portion 8, 10 Shape memory material for bone attachment 9 Shape memory material for fixing bone attachment plate 10a Column portion 10b Arm portion 11 Shape memory material for preventing bone cement outflow 11a Cylindrical plug portion 11b Petal protrusion 12 Shape memory material for preventing vascular restenosis 12b Holes 1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 1
0c, 11c, 12a, 70a Original molded body

─────────────────────────────────────────────────── ─── Continuation of front page (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61L 15/00-33/18 A61B 17/04 A61B 17/58 C08G 63/08 C08L 67/04

Claims (24)

(57) [Claims] 1. A lactic acid-based polymer and bioceramic powder
Is a molded product containing a lactic acid-based polymer
D, L-lactic acid, or D-lactide, L-lactide, D
Any lactide of L (meso) -lactide and glyco
Lido copolymer, caprolactone copolymer,
Copolymer with dioxanone, with ethylene oxide
Copolymer, copolymer with propylene oxide, ethylene
Of all oxide / propylene oxide copolymers
Either alone or as a mixture of several of these copolymers
A shape-memory biodegradable and absorbable material, which is formed of a molded body , and whose shape is restored to a memorized shape even when an external force is not applied, when heated above a predetermined temperature. 2. A lactic acid-based polymer and bioceramic powder
A molded product of a predetermined shape containing lactic acid-based polymer
Is poly-D, L-lactic acid, or D-lactide, L-la.
Lactide of any one of Ctide and DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymers, copolymers with dioxanone, ethylene oxide
Copolymer with side, Copolymer with propylene oxide
Body, ethylene oxide / propylene oxide copolymerization
Any one of these copolymers alone or multiple of these copolymers
A molded body that is a mixture is deformed into a molded body of another shape at a temperature higher than its glass transition temperature and lower than its crystallization temperature (100 ° C when there is no crystallization temperature), and then the temperature is lower than the glass transition temperature as it is. A biodegradable and bioabsorbable material that has been cooled and fixed in shape, and is restored to its original shape in a predetermined shape when heated again above the deformation treatment temperature. Degradable absorbent material. 3. A lactic acid-based polymer and bioceramic powder
A molded product of a predetermined shape containing lactic acid-based polymer
Is poly-D, L-lactic acid, or D-lactide, L-la.
Lactide of any one of Ctide and DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymers, copolymers with dioxanone, ethylene oxide
Copolymer with side, Copolymer with propylene oxide
Body, ethylene oxide / propylene oxide copolymerization
Any one of these copolymers alone or multiple of these copolymers
A molded body that is a mixture is deformed into a molded body of another shape at a temperature higher than its glass transition temperature and lower than its crystallization temperature (100 ° C when there is no crystallization temperature), and then the temperature is lower than the glass transition temperature as it is. After cooling and fixing the shape, this molded body is deformed into a molded body of another shape at a temperature higher than the glass transition temperature and lower than the above deformation treatment temperature, and cooled to a temperature lower than the glass transition temperature as it is. A shape memory biodegradable and absorbable material, which is a biodegradable and absorbable material whose shape is fixed and is restored to the original shape of the molded body when heated again above the initial deformation treatment temperature. Material. 4. A lactic acid-based polymer and bioceramic powder
A porous compact of a predetermined shape which contains the lactate
-Based polymer is poly-D, L-lactic acid or D-lacti
De L-lactide, DL (meso) -lactide
Of lactide and glycolide, caprolact
Tonnes of copolymer, dioxanone copolymer,
Copolymer with Tylene Oxide, Propylene Oxide
Copolymer, ethylene oxide / propylene oxide
Of any one of the copolymers by
A shaped body , which is a mixture of a plurality of bodies, has a crystallization temperature higher than its glass transition temperature (100 in the absence of crystallization temperature).
(° C) is a biodegradable and absorbable material in which a shape is fixed to a substantially non-porous molded body having another shape at a lower temperature, and then cooled to a temperature lower than the glass transition temperature as it is, A shape memory biodegradable and absorbable material, wherein the shape is restored to the original porous body having a predetermined shape when heated again above the deformation treatment temperature. 5. A lactic acid-based polymer and bioceramic powder
A lactic acid-based polymer, which is a cylindrical shaped body containing
Is poly-D, L-lactic acid, or D-lactide or L-lactide.
Lactide, either tide or DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymers, copolymers with dioxanone, ethylene oxide
Copolymer with side, Copolymer with propylene oxide
Body, ethylene oxide / propylene oxide copolymerization
Any one of these copolymers alone or multiple of these copolymers
A shape-memory biodegradable and absorbable material for blood vessel anastomosis , which comprises a molded body which is a mixture, and when heated to a temperature higher than a predetermined temperature, the shape is restored to a memorized small-diameter tubular shape without applying external force. 6. A lactic acid-based polymer and bioceramic powder
A molded body of the small-diameter tubular shape which contains the lactic acid based poly
Is a poly-D, L-lactic acid, or D-lactide, L-
Lactide, either lactide of DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymer, dioxanone-based copolymer, ethylene oxide
Copolymers with oxidants, Copolymers with propylene oxide
Combined, ethylene oxide / propylene oxide
Any one of the polymers or a plurality of these copolymers
The molded body , which is a mixture of the above, is expanded and deformed into a large-diameter cylindrical molded body at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature), and then the glass transition temperature is maintained. It is a biodegradable and absorbable material that has been cooled to a low temperature and fixed in its large-diameter tubular shape, and that when it is heated again above the above deformation treatment temperature, the shape is restored to the original small-diameter tubular shaped body. A shape memory biodegradable and absorbable material for vascular anastomosis. 7. A lactic acid-based polymer and bioceramic powder
A molded body ring shape obtained by containing, lactic acid-based poly
Is a poly-D, L-lactic acid, or D-lactide, L-
Lactide, either lactide of DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymer, dioxanone-based copolymer, ethylene oxide
Copolymers with oxidants, Copolymers with propylene oxide
Combined, ethylene oxide / propylene oxide
Any one of the polymers or a plurality of these copolymers
A shape memory biodegradable and absorbable material for ligating blood vessels, characterized in that the shape is restored to a memorized small-diameter ring shape without applying an external force when it is formed of a molded body that is a mixture of . 8. A lactic acid-based polymer and bioceramic powder
A molded body of the small-diameter tubular shape which contains the lactic acid based poly
Is a poly-D, L-lactic acid, or D-lactide, L-
Lactide, either lactide of DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymer, dioxanone-based copolymer, ethylene oxide
Copolymers with oxidants, Copolymers with propylene oxide
Combined, ethylene oxide / propylene oxide
Any one of the polymers or a plurality of these copolymers
The molded body , which is a mixture of the above, is expanded and deformed into a large-diameter cylindrical molded body at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature), and then the glass transition temperature is maintained. A large-diameter ring-shaped biodegradable and absorbable material that has been cooled to a low temperature and fixed in its large-diameter tubular shape in round slices, and when reheated to above the deformation treatment temperature, the original small-diameter tubular shape A shape-memory biodegradable and absorbable material for ligating blood vessels, characterized in that the shape is restored to a small-diameter ring shape in which the molded body is cut into slices. 9. A lactic acid-based polymer and bioceramic powder
A shaped body of a small diameter ring-shaped which contains a lactic acid-based
The polymer is poly-D, L-lactic acid, or D-lactide,
Either L-lactide or DL (meso) -lactide
Copolymer with cutide and glycolide, caprolactone
Copolymer, dioxanone copolymer, ethylene
Copolymer with propylene oxide, with propylene oxide
By copolymer, ethylene oxide / propylene oxide
Of any one of these copolymers alone or
The molded product, which is a mixture of a plurality of materials, is expanded and deformed into a large-diameter ring-shaped molded product at a temperature higher than the glass transition temperature and lower than the crystallization temperature (100 ° C when there is no crystallization temperature), and the glass transition temperature is maintained as it is. It is a biodegradable and absorbable material that has been cooled to a lower temperature and fixed with its large-diameter ring shape, and the shape can be restored to the original small-diameter ring-shaped molded body when heated again above the above deformation treatment temperature. A shape memory biodegradable and absorbable material for ligating blood vessels, characterized by: 10. A lactic acid-based polymer and bioceramic powder
A flat body having a small opening area and a substantially rectangular tubular shape containing a body , wherein the lactic acid-based polymer is poly-D, L-lactic acid,
Alternatively, D-lactide, L-lactide, DL (meso) -la
Co-weighing with one of the lactides and glycolide
Copolymer, copolymer with caprolactone, dioxanone
Copolymer, ethylene oxide copolymer,
Pyrene oxide copolymer, ethylene oxide / prepolymer
Either of the copolymers of ropylene oxide, either alone or
Is a mixture of a plurality of these copolymers , formed into a substantially rectangular tube shape having a large opening area at a temperature higher than its glass transition temperature and lower than its crystallization temperature (100 ° C. when there is no crystallization temperature). It is a biodegradable and absorbable material in which the body is expanded and deformed, cooled to a temperature lower than the glass transition temperature as it is, and a substantially square tubular shape having a large opening area is fixed, and heated again above the deformation processing temperature. A shape memory biodegradable and absorbable material for tendon junction, characterized in that the shape is restored to the original shape of a substantially rectangular tube having a small flat opening area. 11. A lactic acid-based polymer and bioceramic powder
It is an incised ring-shaped molded body containing the body .
The lactic acid-based polymer is poly-D, L-lactic acid, or D-
Lactide, L-lactide, DL (meso) -lactide
Copolymers and caps of lactide and glycolide
Copolymer with Lactone, Copolymer with Dioxanone
Copolymer, ethylene oxide copolymer, propylene oxide
SID copolymer, ethylene oxide / propylene oxide
Either of the copolymers with xydone or these
It consists of a molded body that is a mixture of multiple copolymers, and when heated above a predetermined temperature, its shape is restored to a memorized small ring incision ring shape without applying external force. Shape memory biodegradable and absorbable material. 12. A lactic acid-based polymer and bioceramic powder
A shaped body of a small diameter ring-shaped which contains the body, lactic acid
-Based polymer is poly-D, L-lactic acid or D-lacti
De L-lactide, DL (meso) -lactide
Of lactide and glycolide, caprolact
Tonnes of copolymer, dioxanone copolymer,
Copolymer with Tylene Oxide, Propylene Oxide
Copolymer, ethylene oxide / propylene oxide
Of any one of the copolymers by
A shaped body , which is a mixture of a plurality of bodies, has a crystallization temperature higher than its glass transition temperature (100 in the absence of crystallization temperature).
(° C), a large-diameter ring-shaped compact was expanded and deformed, cooled to a temperature lower than the glass transition temperature to fix the large-diameter ring, and the large-diameter ring-shaped compact was incised. A biodegradable and bioabsorbable material, which is restored to the original shape by cutting the small-diameter ring-shaped molded product when heated again above the above deformation treatment temperature. Material. 13. A lactic acid-based polymer and bioceramic powder
A shaped body of a small diameter ring-shaped which contains the body, lactic acid
-Based polymer is poly-D, L-lactic acid or D-lacti
De L-lactide, DL (meso) -lactide
Of lactide and glycolide, caprolact
Tonnes of copolymer, dioxanone copolymer,
Copolymer with Tylene Oxide, Propylene Oxide
Copolymer, ethylene oxide / propylene oxide
Of any one of the copolymers by
A shaped body , which is a mixture of a plurality of bodies, has a crystallization temperature higher than its glass transition temperature (100 in the absence of crystallization temperature).
(° C) at a temperature lower than that of the large-diameter ring-shaped formed body by expansion deformation processing, the large-diameter ring-shaped formed body is incised, and one end portion thereof is bent and deformed into a shape that can be engaged with the suture needle, It is a biodegradable and absorbable material that is cooled to a temperature lower than the glass transition temperature and fixed in its shape, and when it is heated again above the above deformation treatment temperature, the original small-diameter ring-shaped molded body is restored to the cut shape. A shape memory biodegradable and absorbable material for suturing, which is characterized in that: 14. A lactic acid-based polymer and bioceramic powder
A lactic acid-based polymer, which is a thread-shaped molded body containing a body
Is poly-D, L-lactic acid, or D-lactide, L-la.
Lactide of any one of Ctide and DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymers, copolymers with dioxanone, ethylene oxide
Copolymer with side, Copolymer with propylene oxide
Body, ethylene oxide / propylene oxide copolymerization
Any one of these copolymers alone or multiple of these copolymers
A shape-memory biodegradable and absorbable material for suture , comprising a molded body which is a mixture, and when heated to a predetermined temperature or higher, the shape is shortened and restored to a stored thick thread shape without applying external force. 15. A lactic acid-based polymer and bioceramic powder
A thick thread-shaped molded body containing a body ,
The limer is poly-D, L-lactic acid, or D-lactide, L
-Lactide, DL (meso) -lactide
Caprolactone, a copolymer of tide and glycolide
Copolymer, dioxanone copolymer, ethylene
Oxide copolymer, propylene oxide copolymer
Polymer, ethylene oxide / propylene oxide
Any one of these copolymers or a mixture of these copolymers
A mixture of several shaped bodies is stretched and deformed at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature) into a shape of a filament longer and thinner than the above-mentioned shaped bodies. However, it is a biodegradable and absorbable material in which the thin thread shape is fixed by cooling it to a temperature lower than the glass transition temperature as it is, and when it is heated again above the deformation treatment temperature, it shortens to form the original thick thread shape. A shape memory biodegradable and absorbable material for suturing, wherein the shape is restored to the body. 16. A lactic acid-based polymer and bioceramic powder
A rod-shaped molded body containing a body , which is a lactic acid-based polymer
Is poly-D, L-lactic acid, or D-lactide, L-la.
Lactide of any one of Ctide and DL (meso) -lactide
And glycolide copolymer, caprolactone
Copolymers, copolymers with dioxanone, ethylene oxide
Copolymer with side, Copolymer with propylene oxide
Body, ethylene oxide / propylene oxide copolymerization
Any one of these copolymers alone or multiple of these copolymers
A shape memory raw material for osteosynthesis, characterized by comprising a molded body that is a mixture, and when heated above a predetermined temperature, its shape is restored to a memorized rod shape thicker and shorter than the above rod shape without applying external force. Biodegradable and absorbable material. 17. A lactic acid-based polymer and bioceramic powder
A molded article of a thick rod shape which contains the body, lactic acid-based port
The limer is poly-D, L-lactic acid, or D-lactide, L
-Lactide, DL (meso) -lactide
Caprolactone, a copolymer of tide and glycolide
Copolymer, dioxanone copolymer, ethylene
Oxide copolymer, propylene oxide copolymer
Polymer, ethylene oxide / propylene oxide
Any one of these copolymers or a mixture of these copolymers
A mixture of a number of molded bodies is deformed into a rod-shaped molded body longer and thinner than the above-mentioned molded body at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature). , A biodegradable and absorbable material in which the thin rod shape is fixed by cooling to a temperature lower than the glass transition temperature as it is, and when heated again above the deformation treatment temperature, the shape of the original thick rod-shaped molded body is changed. A shape memory biodegradable and absorbable material for osteosynthesis characterized by being restored. 18. The shape memory material according to claim 17, wherein the molded body which has been deformed into a long and thin rod shape is cooled to fix the shape and further cut into a predetermined pin shape. Biodegradable and absorbable material. 19. A molded body containing a bioceramic powder in a lactic acid-based polymer , which has a shape in which two or more arm portions are inclined and protruded outward from the peripheral edges of both end faces of a cylindrical portion.
And the lactic acid-based polymer is poly-D, L-lactic acid,
Is D-lactide, L-lactide, DL (meso) -lac
Copolymerization with glycolide with one of the lactides
And copolymers of caprolactone and dioxanone
Copolymer, ethylene oxide copolymer, propene
Copolymer with lenoxide, ethylene oxide / pro
Pyrene oxide copolymer either alone or
A molded body , which is a mixture of a plurality of these copolymers, is treated at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature), and each arm portion is aligned with the axial direction of the cylindrical portion. A biodegradable and absorbable material that is bent and deformed inward at the base of each arm so that it is parallel, and then cooled to a temperature lower than the glass transition temperature to fix its shape. A shape memory biodegradable and absorbable material for osteosynthesis, wherein the shape is restored to the original molded body when heated again. 20. Bioseed to a lactic acid-based polymer having a shape in which two or more petal-shaped protrusions are inclined and protruded outward from the peripheral edge of the upper surface of a cylindrical plug portion having a hemispherical lower surface.
A molded product containing Lamix powder , which is a lactic acid-based powder.
The limer is poly-D, L-lactic acid, or D-lactide, L
-Lactide, DL (meso) -lactide
Caprolactone, a copolymer of tide and glycolide
Copolymer, dioxanone copolymer, ethylene
Oxide copolymer, propylene oxide copolymer
Polymer, ethylene oxide / propylene oxide
Any one of these copolymers or a mixture of these copolymers
A mixture of a number of molded bodies at a temperature higher than the glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature) so that each petal-shaped protrusion is parallel to the axial direction of the cylindrical plug. It is a biodegradable and absorbable material that is bent and deformed inward at the root of each petal-shaped protrusion so that it is cooled to a temperature lower than the glass transition temperature and its shape is fixed. A shape memory biodegradable and absorbable material for preventing bone cement outflow in the medullary cavity, characterized in that the shape is restored to the original molded body when heated again. 21. having a mesh-like cylindrical shape with a plurality of perforated cylindrical or mesh with a hole was formed, moldings der which contains a bioceramics powder in lactic acid-based polymer
Therefore, the lactic acid-based polymer is poly-D, L-lactic acid, or D
Of lactide, L-lactide, DL (meso) -lactide
Copolymer with either lactide and glycolide
Copolymer with prolactone, Copolymer with dioxanone
Copolymer, copolymer with ethylene oxide, propylene oxide
Copolymer with xide, ethylene oxide / propylene
Oxide copolymers either alone or these
The molded product, which is a mixture of a plurality of copolymers, is bent and deformed at a temperature higher than its glass transition temperature and lower than the crystallization temperature (100 ° C. when there is no crystallization temperature) into a bent cylindrical molded product. However, it is a biodegradable and absorbable material whose shape is fixed by cooling it to a temperature lower than the glass transition temperature as it is, and that the shape is restored to the original molded body when heated again above the deformation treatment temperature. A shape-memory biodegradable and absorbable material for preventing vascular restenosis. 22. Poly-D, L-lactic acid is obtained by ring-opening polymerization of DL (meso) -lactide, a copolymer obtained by ring-opening polymerization of a mixture of D-lactide and L-lactide. 22. Any one of the following copolymers, a copolymer obtained by polymerizing a mixture of L-lactic acid and D-lactic acid, or a mixture thereof. The shape memory biodegradable and absorbable material according to claim 1. 23. The bioceramics powder is a surface bioactive hydroxyapatite, bioglass or crystallized glass biomedical glass, bioabsorbable wet hydroxyapatite, dicalcium phosphate, tricalcium phosphate, tetracalcium. The shape memory biodegradable and absorbable material according to any one of claims 1 to 22, wherein any one of a phosphate, an octacalcium phosphate, a calcite, and a diopsite, or a mixture of two or more thereof. 24. The shape memory biodegradable and absorbable material according to any one of claims 1 to 23, wherein the material contains a drug.