JP2000197693A - Porous adhesion preventive material - Google Patents
Porous adhesion preventive materialInfo
- Publication number
- JP2000197693A JP2000197693A JP11285489A JP28548999A JP2000197693A JP 2000197693 A JP2000197693 A JP 2000197693A JP 11285489 A JP11285489 A JP 11285489A JP 28548999 A JP28548999 A JP 28548999A JP 2000197693 A JP2000197693 A JP 2000197693A
- Authority
- JP
- Japan
- Prior art keywords
- adhesion
- porous
- tendon
- caprolactone
- lactic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Polyesters Or Polycarbonates (AREA)
- Materials For Medical Uses (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、腱損傷の治療の際
に腱の癒着を防止するために用いられる多孔性癒着防止
材に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a porous anti-adhesion material used for preventing tendon adhesion when treating tendon damage.
【０００２】[0002]
【従来の技術】腱損傷に対する治療法としては、断裂し
た腱を縫合した後、患部をギプス固定する間に腱を癒合
させ、リハビリを行なって患部を正常な状態に再建する
方法が現在の主流となっている。治療のポイントとして
は、再断裂を防ぐための強固な縫合がなされることと、
早期（術後２週目程度）からリハビリを開始することが
挙げられる。しかし、骨折を伴う場合や損傷が広範囲に
およぶ場合は、早期のリハビリ開始が不可能となり、癒
着の原因となる。2. Description of the Related Art As a treatment method for tendon damage, a method of reconstructing an affected part by rehabilitating the affected part by rehabilitating the torn part after the torn tendon is sutured, and the affected part is cast by fixing the affected part, is now mainstream. It has become. The point of treatment is that strong sutures are made to prevent re-tearing,
Starting rehabilitation from an early stage (about two weeks after surgery) can be cited. However, when a fracture is involved or the damage is widespread, early rehabilitation cannot be started, causing adhesion.
【０００３】例えば、屈筋腱や腱鞘の修復後の癒着は手
術法の発達や術後早期リハビリの導入によってある程度
まで防止できるようになってきた。しかし、早期自動他
動運動が不可能な場合やｇｒｉｄｉｎｇ ｂａｓｅが不
良な場合には、一定期間、腱の癒着を防止し、腱鞘の再
生とともに吸収される材料の使用が望ましい。For example, adhesion after repair of flexor tendons and tendon sheaths can be prevented to some extent by the development of surgical methods and the introduction of early postoperative rehabilitation. However, when the automatic passive exercise cannot be performed early or the gridding base is poor, it is desirable to use a material that prevents adhesion of the tendon for a certain period of time and is absorbed together with regeneration of the tendon sheath.
【０００４】特に、手の外科の領域においては、事故な
どで受傷した手指の機能回復は大きなテーマとなってお
り、指の屈曲運動を担う腱（ＺｏｎｅIIにおける屈腱
筋）が断裂した場合、上記のような重篤な症状では、ギ
プス固定が長期に及ぶため、その間運動が許されない屈
腱筋は周辺組織と癒着を引き起こしやすい。この屈腱筋
の術後癒着は、指の屈曲機能に障害を与える大きな原因
のひとつである。In the field of hand surgery, in particular, the recovery of the function of a finger injured in an accident or the like is a major theme, and when a tendon (flexor tendon in Zone II) responsible for the bending motion of the finger is torn, the above-mentioned problem occurs. In such a severe condition, since the cast is fixed for a long period of time, the tendon muscles that are not allowed to exercise during the fixation tend to cause adhesion with surrounding tissues. This postoperative adhesion of the tendon flexor is one of the major causes of impairment of the flexion function of the finger.
【０００５】このような癒着を防止するために、液状や
膜状のヒアルロン酸、コラーゲンシート、ポリグラクチ
ン９１０メッシュ、ポリテトラフルオロエチレン膜、シ
リコン膜、架橋ゼラチン膜等が癒着防止材として使用さ
れてきたが、操作性、癒着防止効果及び生体吸収性の全
てを満足するものではなかった。In order to prevent such adhesion, liquid or film-like hyaluronic acid, collagen sheet, polyglactin 910 mesh, polytetrafluoroethylene film, silicon film, cross-linked gelatin film and the like have been used as adhesion preventing materials. However, it did not satisfy all of the operability, the adhesion preventing effect, and the bioabsorbability.
【０００６】[0006]
【発明が解決しようとする課題】本発明の目的は、適度
な生体吸収性を持って腱とその周辺組織を物理的に隔離
でき、かつ操作性、栄養物質の透過性及び安全性に優れ
た腱の癒着防止材を提供することにある。SUMMARY OF THE INVENTION It is an object of the present invention to be able to physically isolate a tendon and its surrounding tissue with an appropriate bioabsorbability, and to provide excellent operability, permeability of nutrient substances and safety. An object of the present invention is to provide a tendon adhesion preventing material.
【０００７】[0007]
【課題を解決するための手段】前記課題を解決するため
に、本発明の多孔性癒着防止材は、乳酸とカプロラクト
ンとの共重合体からなることを特徴とする。Means for Solving the Problems In order to solve the above-mentioned problems, the porous adhesion preventing material according to the present invention is characterized by comprising a copolymer of lactic acid and caprolactone.
【０００８】尚、本発明の多孔性癒着防止材において、
前記共重合体の重量平均分子量は５０，０００〜５０
０，０００の範囲が好ましく、前記共重合体中の乳酸と
カプロラクトンとの共重合割合は、重量比で乳酸／カプ
ロラクトン＝８０／２０〜３０／７０の範囲が好まし
い。[0008] In the porous anti-adhesion material of the present invention,
The weight average molecular weight of the copolymer is from 50,000 to 50.
It is preferably in the range of 000, and the copolymerization ratio of lactic acid and caprolactone in the copolymer is preferably in the range of lactic acid / caprolactone = 80/20 to 30/70 by weight.
【０００９】また、本発明の多孔性癒着防止材におい
て、多孔の平均孔径は０．１〜８０μｍの範囲（さらに
好ましくは０．５〜５０μｍの範囲）が好ましく、空隙
率は４０〜９５％の範囲が好ましい。In the porous anti-adhesion material of the present invention, the average pore diameter is preferably in the range of 0.1 to 80 μm (more preferably in the range of 0.5 to 50 μm), and the porosity is preferably in the range of 40 to 95%. A range is preferred.
【００１０】本発明の多孔性癒着防止材において、さら
に、ヒアルロン酸を含有することが好ましい。これによ
り、一層、腱と腱の周辺組織とが癒着することを防止す
ることが可能になる。本発明の多孔性癒着防止材におい
て、ヒアルロン酸は、例えば、前記共重合体からなる多
孔質材に予め保持させてもよいし、使用時に保持させて
もよい。なお、ヒアルロン酸が流れ易い場合に、このよ
うに多孔質癒着防止材に含有させることによって、ヒア
ルロン酸の流失を防止できるという効果もある。It is preferable that the porous anti-adhesion material of the present invention further contains hyaluronic acid. Thereby, it is possible to further prevent the adhesion between the tendon and the tissue surrounding the tendon. In the porous adhesion preventive material of the present invention, the hyaluronic acid may be held in advance, for example, in the porous material made of the copolymer, or may be held when used. In addition, when hyaluronic acid flows easily, by including it in the porous adhesion preventing material in this way, there is also an effect that the loss of hyaluronic acid can be prevented.
【００１１】本発明の多孔性癒着防止材において、ヒア
ルロン酸の含量が、多孔性癒着防止材全体の０．１〜１
０重量％の範囲であることが好ましい。In the porous anti-adhesion material of the present invention, the content of hyaluronic acid is 0.1 to 1 of the entire porous anti-adhesion material.
It is preferably in the range of 0% by weight.
【００１２】さらに、本発明の多孔性癒着防止材は、腱
損傷の治療の際に腱の癒着を防止するために用いられる
ことが好ましい。Further, it is preferable that the porous adhesion preventing material of the present invention is used for preventing adhesion of tendon when treating tendon damage.
【００１３】[0013]
【発明の実施の形態】本発明において使用する乳酸とカ
プロラクトンとの共重合体において、乳酸としてはＬ−
乳酸を使用することが好ましい。カプロラクトンとして
は、ε−カプロラクトン、γ−カプロラクトン、δ−カ
プロラクトン等が挙げられるが、ε−カプロラクトンが
好ましい。BEST MODE FOR CARRYING OUT THE INVENTION In the copolymer of lactic acid and caprolactone used in the present invention, the lactic acid is L-
Preference is given to using lactic acid. Examples of caprolactone include ε-caprolactone, γ-caprolactone, δ-caprolactone, and the like, with ε-caprolactone being preferred.
【００１４】前記共重合体の重量平均分子量（Ｍｗ）
は、５０，０００〜５００，０００の範囲が好ましく、
さらに好ましくは２００，０００〜４００，０００の範
囲である。重量平均分子量が５０，０００未満の場合
は、例えば、多孔体として用いた場合、強度が不十分と
なり術中に破損しやすく、医用材料に適さないおそれが
ある。一方、重量平均分子量が５００，０００を超える
と、例えば、剛性が高く、腱に巻き付けることが困難と
なるおそれがある。Weight average molecular weight (Mw) of the copolymer
Is preferably in the range of 50,000 to 500,000,
More preferably, it is in the range of 200,000 to 400,000. When the weight average molecular weight is less than 50,000, for example, when used as a porous body, the strength is insufficient, and it is liable to be broken during surgery, which may not be suitable for a medical material. On the other hand, when the weight average molecular weight exceeds 500,000, for example, the rigidity may be high, and it may be difficult to wrap around the tendon.
【００１５】前記共重合体中の乳酸とカプロラクトンと
の共重合割合は、重量比で、乳酸／カプロラクトン＝８
０／２０〜３０／７０の範囲が好ましく、さらに好まし
くは、乳酸／カプロラクトン＝６５／３５〜４５／５５
の範囲である。乳酸／カプロラクトン重量比が３０／７
０未満の場合は、例えば、剛性が高く、腱に巻き付ける
ことが困難となり、一方、８０／２０を超えても、剛性
が高く、腱に巻き付けることが困難となるおそれがあ
る。The copolymerization ratio of lactic acid and caprolactone in the copolymer is lactic acid / caprolactone = 8 by weight.
The range is preferably 0/20 to 30/70, more preferably lactic acid / caprolactone = 65/35 to 45/55.
Range. Lactic acid / caprolactone weight ratio is 30/7
If it is less than 0, for example, the rigidity is high, and it is difficult to wind it around the tendon. On the other hand, if it exceeds 80/20, the rigidity is high, and it may be difficult to wind it around the tendon.
【００１６】尚、前記共重合体には、乳酸とカプロラク
トン以外の共重合体成分として、例えば、グリコール酸
やバレロラクトン等の脂肪族エステルや、１，４−ジオ
キサノン−２−オン、１，５−ジオキセパン−２−オ
ン、エチレングリコール等を、本発明の効果を損なわな
い範囲で共重合させることも可能である。The above-mentioned copolymer includes, as copolymer components other than lactic acid and caprolactone, for example, aliphatic esters such as glycolic acid and valerolactone, 1,4-dioxanone-2-one, 1,5 It is also possible to copolymerize -dioxepan-2-one, ethylene glycol and the like within a range that does not impair the effects of the present invention.
【００１７】前記共重合体の製造方法としては、例え
ば、常法により、ラクチド（乳酸の環状二量体）とε−
カプロラクトンとを開環重合することにより得る方法等
が挙げられる。As a method for producing the copolymer, for example, lactide (cyclic dimer of lactic acid) and ε-
And a method obtained by ring-opening polymerization of caprolactone.
【００１８】前記共重合体を多孔質体に成形する方法と
しては、通常の多孔質成形法、例えば、前記共重合体と
発泡体とをフィルム状に射出成形して多孔性フィルムを
得る方法、前記共重合体と水溶性塩とを混在させ、プレ
ス法やキャスト法等によりフィルムを作製し、前記フィ
ルムを水洗することで塩を除去して多孔性フィルムを得
る方法、前記共重合体を溶剤に溶解させ、その溶剤を凍
結乾燥することで多孔性フィルムを得る方法等があげら
れる。このような方法により、前記共重合体を多孔性の
成形物とし、本発明の多孔性癒着防止材として使用する
ことができる。As a method for forming the above-mentioned copolymer into a porous body, a conventional method for forming a porous body, for example, a method for injection-molding the above-mentioned copolymer and foam into a film to obtain a porous film, A method of obtaining a porous film by mixing the copolymer and a water-soluble salt, producing a film by a pressing method, a casting method, or the like, and removing a salt by washing the film with water to obtain a porous film, And a method of obtaining a porous film by freeze-drying the solvent. By such a method, the copolymer can be formed into a porous molded product and used as the porous adhesion preventive material of the present invention.
【００１９】本発明の多孔性癒着防止材の厚みは、１０
〜１０００μｍの範囲が好ましく、さらに好ましくは５
０〜４００μｍの範囲である。多孔の平均孔径は、０．
１〜８０μｍの範囲が好ましく、さらに好ましくは０．
５〜５０μｍの範囲、特に好ましくは５〜２０μｍの範
囲である。前記平均孔径が０．１μｍ未満の場合は、例
えば、癒着防止材を通して体液交換が充分に行なわれ
ず、癒着防止材で覆った患部の中心部まで栄養が行き渡
らないおそれがある。一方、前記平均孔径が８０μｍを
超えると、例えば、再生した組織が癒着防止材の孔に侵
入することにより、バリア性が低下して癒着防止が低下
するおそれがある。尚、癒着防止効果の点からは、多孔
の平均孔径は、０．５〜５０μｍの範囲であることが特
に望ましい。The thickness of the porous anti-adhesion material of the present invention is 10
To 1000 μm, more preferably 5 μm.
The range is from 0 to 400 μm. The average pore size of the porosity is 0.
The range is preferably from 1 to 80 µm, more preferably from 0.
The range is 5 to 50 μm, particularly preferably 5 to 20 μm. When the average pore diameter is less than 0.1 μm, for example, the body fluid exchange may not be sufficiently performed through the adhesion preventing material, and nutrition may not reach the central part of the affected area covered with the adhesion preventing material. On the other hand, if the average pore diameter exceeds 80 μm, for example, the regenerated tissue may enter the pores of the adhesion preventing material, and the barrier property may be reduced, and the prevention of adhesion may be reduced. In addition, from the viewpoint of the adhesion preventing effect, it is particularly desirable that the average pore diameter of the porosity is in the range of 0.5 to 50 μm.
【００２０】本発明においては、このような多孔質体と
することにより、癒着防止材を通して体液の交換が可能
となり、電気メスによる固定が可能となる。In the present invention, by using such a porous body, body fluid can be exchanged through the adhesion preventing material, and fixation by an electric knife becomes possible.
【００２１】また、本発明の多孔性癒着防止材の空隙率
は、４０〜９５％の範囲が好ましく、さらに好ましくは
６０〜９０％の範囲である。空隙率が４０％未満の場合
は、例えば、剛性が高くなり、癒着防止材としての柔軟
性が減少したり、また、体液の交換が充分に行なわれ
ず、電気メスが安定して使えないおそれがある。一方、
空隙率が９５％を超えると、例えば、強度が小さいため
操作性が悪くなり、術中に破損しやすくなるおそれがあ
る。The porosity of the porous anti-adhesion material of the present invention is preferably in the range of 40 to 95%, more preferably in the range of 60 to 90%. When the porosity is less than 40%, for example, the rigidity is increased, the flexibility as the adhesion preventing material is reduced, or the body fluid is not sufficiently exchanged, so that the electric knife may not be used stably. is there. on the other hand,
When the porosity exceeds 95%, for example, the operability is deteriorated due to the low strength, and the porosity may be easily damaged during the operation.
【００２２】また、本発明の多孔性癒着防止材は、前述
のように、さらにヒアルロン酸を含有してもよい。前記
ヒアルロン酸の含量は、多孔性癒着防止材全体の０．１
〜１０重量％の範囲であることが好ましく、さらに好ま
しくは０．５〜５重量％の範囲である。Further, as described above, the porous adhesion preventive material of the present invention may further contain hyaluronic acid. The content of the hyaluronic acid is 0.1% of the entire porous adhesion preventing material.
It is preferably in the range of 10 to 10% by weight, and more preferably in the range of 0.5 to 5% by weight.
【００２３】このようなヒアルロン酸を含有する多孔性
癒着防止材は、例えば、前述のような共重合体からなる
多孔質性の成形体を、ヒアルロン酸溶液に浸漬させ、こ
れを凍結乾燥等により乾燥することにより製造できる。
前記ヒアルロン酸溶液の濃度は、０．０５〜１０重量％
の範囲であることが好ましく、さらに好ましくは０．５
〜１重量％の範囲である。前記ヒアルロン酸溶液は、例
えば、ヒアルロン酸粉末を、水、生理食塩水等に溶解す
ればよい。なお、前記ヒアルロン酸は、乾燥状態で含有
されてもよいし、液状で含有されてもよい。前記ヒアル
ロン酸の重量平均分子量は、例えば、６０万〜３９０万
の範囲であり、好ましくは、６０万〜１２０万の範囲で
ある。The porous anti-adhesion material containing hyaluronic acid can be obtained by, for example, immersing a porous molded article made of the above-described copolymer in a hyaluronic acid solution and freeze-drying the same. It can be manufactured by drying.
The concentration of the hyaluronic acid solution is 0.05 to 10% by weight.
And more preferably 0.5
-1% by weight. The hyaluronic acid solution may be prepared, for example, by dissolving hyaluronic acid powder in water, physiological saline, or the like. The hyaluronic acid may be contained in a dry state or in a liquid state. The weight average molecular weight of the hyaluronic acid is, for example, in a range of 600,000 to 3.9 million, and preferably in a range of 600,000 to 1.2 million.
【００２４】また、前述のように、例えば、使用時に、
前記共重合体からなる多孔性成形体を腱に巻き付け、こ
れに前記ヒアルロン酸溶液を注入してもよい。As described above, for example, at the time of use,
The porous molded body made of the copolymer may be wound around a tendon, and the hyaluronic acid solution may be injected into the wound.
【００２５】[0025]
【実施例】以下、実施例により本発明をさらに具体的に
説明するが、本発明はこれに限定されるものではない。
尚、以下の例において、空隙率及び癒着発生率以外の
「％」は「重量％」である。EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
In the following examples, “%” other than the porosity and the adhesion occurrence rate is “% by weight”.
【００２６】（実施例１）Ｌ−乳酸とε−カプロラクト
ンとの共重合体（Ｍｗ４０万、乳酸とカプロラクトンと
の共重合体中における重量比：乳酸／カプロラクトン＝
５５／４５）の６重量％ジオキサン溶液をガラス板上に
キャストし、そのガラス板を−１３５℃の冷凍庫内に投
入して、前記溶液を凍結した。その後、凍結乾燥器で溶
剤（ジオキサン）を除去することにより、孔径約１０μ
ｍ（ほぼ均一な孔径であり、平均孔径１０μｍ）、空隙
率８８％、厚み４００μｍの多孔質膜を得た。この多孔
質膜を多孔性癒着防止材として用い、下記に示すニワト
リ足部屈筋腱損傷モデルによる操作性及び癒着防止効果
の評価（３週間埋入後の癒着スコア並びに３週間埋入後
及び１２週間埋入後の肉眼による観察）を行なった。(Example 1) Copolymer of L-lactic acid and ε-caprolactone (Mw 400,000, weight ratio in copolymer of lactic acid and caprolactone: lactic acid / caprolactone =
A 55% / 45% by weight dioxane solution was cast on a glass plate, and the glass plate was placed in a -135 ° C freezer to freeze the solution. Thereafter, the solvent (dioxane) is removed with a freeze dryer to obtain a pore size of about 10 μm.
m (having a substantially uniform pore size and an average pore size of 10 μm), a porosity of 88%, and a thickness of 400 μm. Using this porous membrane as a porous adhesion-preventing material, evaluation of operability and adhesion-preventing effect by a chicken foot flexor tendon injury model shown below (adhesion score after 3 weeks implantation, and 3 weeks after implantation and 12 weeks after implantation) Observation with the naked eye after implantation).
【００２７】その結果、試験サンプル数１４例のうち４
例には、ギプス固定時の過度の圧迫によると思われる炎
症変化が見られたため、癒着防止効果を評価する対象か
ら除外した。実施例における癒着スコアの１０例の平均
値は１．９点であった。また、本実施例の多孔性癒着防
止材は、電気メスを用いて前記癒着防止材同志を融着さ
せることにより、縫合せずに局部に固定することが可能
であり、操作性に優れるものであった。As a result, 4 out of 14 test samples
Examples showed inflammatory changes presumably due to excessive compression during casting, and were therefore excluded from the evaluation of the anti-adhesion effect. The average value of the adhesion scores in 10 cases in the examples was 1.9 points. Further, the porous anti-adhesion material of this embodiment can be fixed to a local portion without sewing by fusing the anti-adhesion materials with each other using an electric scalpel, and is excellent in operability. there were.
【００２８】また、肉眼観察の結果、前記多孔性癒着防
止材は、埋入後３週目においては、埋入時と変わらずほ
ぼ同じ場所を覆っていたが、１２週目においては、肉眼
的に消失しており細かい残骸となって腱周辺に存在して
いた。Further, as a result of a visual observation, the porous adhesion preventing material covered almost the same place at the third week after implantation as in the time of implantation. And disappeared as fine debris around the tendon.
【００２９】尚、平均孔径、重量平均分子量（Ｍｗ）及
び共重合体の組成比の測定方法を以下に示す。The methods for measuring the average pore size, the weight average molecular weight (Mw) and the composition ratio of the copolymer are described below.
【００３０】（操作性及び癒着防止効果の測定方法）ニ
ワトリ（赤玉鶏もみじ、５月齢：以下、同じ）を用い、
その第３趾の中央部の皮膚を約１０ｍｍ切開した後、腱
鞘を切開して前記腱鞘中の深趾屈筋腱を露出させた。そ
して、切開部中央約５ｍｍの部分にある腱周辺組織にバ
イポーラ電気メスで熱傷を与え、損傷部とした。前記損
傷部と接する腱部分に、長さ１０ｍｍ、幅１５ｍｍの多
孔性癒着防止材を巻き付けてから、バイポーラ電気メス
により前記癒着防止材同士を融着固定し、余分な材料は
切除した。次に、５−０ナイロン糸で切開部を縫合し、
術後３週間は指伸展位にてギプス固定を行なった。前記
癒着防止材を埋入してから３週間及び１２週間（ギプス
固定後９週間自由運動）後に、ジエチルエーテルを大量
吸入させてニワトリを犠牲死させた。その後、手術部位
を腱に沿って鋭的に割断し、同一の整形外科医による目
視二重盲検法によって、癒着程度を以下の基準で評価し
た。尚、下記に示す癒着スコアの点数が低いほど癒着は
なく、癒着スコアの点数が高いほど重度の癒着が生じて
いると判断できる。(Method for Measuring Operability and Adhesion Prevention Effect) Using chicken (Akatama chicken maple, 5 months old; the same applies hereinafter),
After incising about 10 mm of the skin at the center of the third toe, the tendon sheath was incised to expose the flexor tendon muscle tendon in the tendon sheath. Then, a tissue around the tendon at the center of the incision at a distance of about 5 mm was burned with a bipolar electric scalpel to obtain a damaged portion. A 10 mm long, 15 mm wide porous anti-adhesion material was wrapped around the tendon portion in contact with the damaged portion, and the anti-adhesion materials were fused and fixed together with a bipolar electric scalpel, and excess material was cut off. Next, the incision is sutured with 5-0 nylon thread,
For three weeks after the operation, the cast was fixed at the finger extension position. After 3 weeks and 12 weeks (free movement for 9 weeks after casting), a large amount of diethyl ether was inhaled and the chickens were sacrificed three weeks after the adhesion preventing material was implanted. Thereafter, the surgical site was severely cut along the tendon, and the degree of adhesion was evaluated by the same orthopedic surgeon by the visual double-blind method according to the following criteria. The lower the score of the adhesion score shown below, the lower the adhesion, and the higher the score of the adhesion score, the more severe the adhesion.
【００３１】癒着程度の評価基準（癒着スコア） １：Ｗｉｔｈｏｕｔ ａｄｈｅｓｉｏｎ ２：Ｆｉｌｍｙ（ｓｅｐａｒａｂｌｅ） ３：Ｍｉｌｄ（ｎｏｔ ｓｅｐａｒａｂｌｅ） ４：Ｍｏｄｅｒａｔｅ（３５〜６０％） ５：Ｓｅｖｅｒｅ（＞６０％）Evaluation criteria of adhesion degree (adhesion score) 1: Without adhesion 2: Filmy (separable) 3: Mild (not separateable) 4: Moderate (35-60%) 5: Severe (> 60%)
【００３２】（平均孔径の測定方法）多孔性癒着防止材
を電子顕微鏡により拡大撮影した。その写真を用いて、
一定範囲内の最前列の孔のサイズを測定し、その平均値
を平均孔径とした。(Measurement Method of Average Pore Size) The porous anti-adhesion material was enlarged and photographed with an electron microscope. Using that photo,
The size of the front row of holes within a certain range was measured, and the average value was defined as the average pore diameter.
【００３３】（重量平均分子量（Ｍｗ）の測定方法）多
孔性癒着防止材２０ｍｇをクロロホルムに溶解し、ＧＰ
Ｃ：ゲルパーミエーションクロマトグラフィー（展開溶
媒：クロロホルム）を用いて、標準ポリスチレン換算に
より重量平均分子量を測定した。(Method for measuring weight average molecular weight (Mw)) 20 mg of a porous anti-adhesion material was dissolved in chloroform,
C: The weight average molecular weight was measured by gel permeation chromatography (developing solvent: chloroform) in terms of standard polystyrene.
【００３４】（共重合体組成の測定方法）乾燥した乳酸
−カプロラクトン共重合体を用いて、1Ｈの核磁気共鳴
スペクトル測定を行なった。５．２ｐｐｍ付近を乳酸、
４．１ｐｐｍ付近をカプロラクトンのピークとし、その
ピークの積分値比によりラクチドとカプロラクトンとの
モル比率を求め、それを重量換算することにより重量比
を求めた。(Method of Measuring Copolymer Composition) Using a dried lactic acid-caprolactone copolymer, 1 H nuclear magnetic resonance spectrum was measured. Lactic acid around 5.2 ppm
The peak of caprolactone was set around 4.1 ppm, the molar ratio of lactide and caprolactone was determined from the integrated value ratio of the peak, and the weight ratio was determined by converting it to the weight.
【００３５】（実施例２）Ｌ−乳酸とε−カプロラクト
ンとの共重合体（Ｍｗ４０万、乳酸とカプロラクトンと
の共重合体中における重量比：乳酸／カプロラクトン＝
５５／４５）の６重量％ジオキサン溶液をガラス板上に
キャストし、そのガラス板を−３０℃の冷凍庫内に投入
して前記溶液を凍結した。その後、凍結乾燥器にて溶剤
（ジオキサン）を除去することにより、孔径２０〜１０
０μｍ（平均孔径８０μｍ）、空隙率８５％、厚み６０
０μｍの多孔質膜を得た。この多孔質膜を多孔性癒着防
止材として用い、前記実施例１と同様にして、操作性及
び癒着防止効果の評価を行なった。Example 2 Copolymer of L-lactic acid and ε-caprolactone (Mw 400,000, weight ratio in copolymer of lactic acid and caprolactone: lactic acid / caprolactone =
A 55% / 45% by weight dioxane solution was cast on a glass plate, and the glass plate was put into a freezer at -30 ° C to freeze the solution. After that, the solvent (dioxane) is removed by a freeze dryer, so that the pore diameter is 20 to 10.
0 μm (average pore diameter 80 μm), porosity 85%, thickness 60
A 0 μm porous membrane was obtained. Using this porous membrane as a porous adhesion preventing material, the operability and the adhesion preventing effect were evaluated in the same manner as in Example 1.
【００３６】その結果、試験サンプル数９例のうち４例
にギプス固定時の過度の圧迫によると思われる炎症変化
が見られたため、癒着防止効果を評価する対象から除外
した。癒着スコアの５例の平均値は３．０点であった。
また、この癒着防止材は、前述と同様に、電気メスを用
いて前記癒着防止材同士を融着させることにより、縫合
せずに局部に固定することが可能であり、操作性に優れ
るものであった。As a result, four out of nine test samples showed inflammatory changes presumably due to excessive compression during casting, and were excluded from the subjects for evaluation of the adhesion preventing effect. The average value of the adhesion scores in the five cases was 3.0 points.
In addition, this adhesion preventing material can be fixed to a local portion without sewing by fusing the adhesion preventing materials to each other using an electric scalpel as described above, and is excellent in operability. there were.
【００３７】また、肉眼観察の結果、前記多孔性融着防
止材は、埋入後３週目においては、埋入時と変わらずほ
ぼ同じ場所を覆っていたが、１２週目においては、肉眼
的に消失しており細かい残骸となって腱周辺に存在して
いた。As a result of visual observation, it was found that the porous anti-fusing material covered almost the same place in the third week after implantation as in the time of implantation, but in the 12th week, It disappeared and became fine remnants around the tendon.
【００３８】（比較例１）損傷部に多孔性癒着防止材を
使用せずに、そのまま閉創した以外は、前記実施例１と
同様にして操作を行ない、癒着防止効果の評価を行なっ
た。(Comparative Example 1) An operation was performed in the same manner as in Example 1 except that the wound was not wound and the porous adhesion preventing material was not used, and the adhesion preventing effect was evaluated.
【００３９】その結果、試験サンプル数１５例のうち５
例に、ギプス固定時の過度の圧迫によると思われる炎症
変化が見られたため、癒着防止効果を評価する対象から
除外した。１０例の癒着スコアの平均値は、３．８点で
あった。As a result, 5 out of 15 test samples
In an example, an inflammatory change which was considered to be caused by excessive compression when the cast was fixed was excluded from the subject for which the anti-adhesion effect was evaluated. The average value of the adhesion score of 10 cases was 3.8 points.
【００４０】また、肉眼観察の結果、腱組織は、術後３
週目において、一部又は腱の全周に渡って周辺組織と癒
着を起こしていた。As a result of the visual observation, the tendon tissue was found to be 3 postoperatively.
At week, adhesions had occurred with surrounding tissue over part or the entire circumference of the tendon.
【００４１】（比較例２）多孔性癒着防止材の代りに、
厚み１００μｍの熱架橋したゼラチンフィルムを使用し
た以外は、実施例１と同様に操作を行ない、操作性及び
癒着防止効果の評価を行なった。(Comparative Example 2) Instead of the porous adhesion preventing material,
The operation was performed in the same manner as in Example 1 except that a thermally crosslinked gelatin film having a thickness of 100 μm was used, and the operability and the adhesion preventing effect were evaluated.
【００４２】その結果、試験サンプル数３例の癒着スコ
ア平均値は２点であった。前記ゼラチンフィルムをうま
く腱に巻き付けることができず、また、腱への固定に用
いた縫合糸が前記ゼラチンフィルムを破損してしまいや
すかったため、操作性は良好とは言えなかった。また、
肉眼観察の結果、前記ゼラチンフィルムは、術後３週間
目において、肉眼的に消失していた。As a result, the average value of the adhesion scores of the three test samples was two. The operability was not good because the gelatin film could not be wound around the tendon well, and the suture used for fixing to the tendon was liable to damage the gelatin film. Also,
As a result of macroscopic observation, the gelatin film had disappeared macroscopically three weeks after the operation.
【００４３】上記の実施例１〜２及び比較例１〜２の結
果からわかるように、実施例１の多孔性癒着防止材が癒
着防止効果において最も良好な結果を示した。これは適
度な孔径を持つ実施例の癒着防止材においては、腱周辺
組織の細胞が孔内に侵入することが抑制されたためと考
えられる。As can be seen from the results of Examples 1 and 2 and Comparative Examples 1 and 2, the porous anti-adhesion material of Example 1 showed the best results in the anti-adhesion effect. This is presumably because in the anti-adhesion material of the embodiment having an appropriate pore diameter, the cells of the tissue around the tendon were prevented from entering the pores.
【００４４】尚、実施例１〜２の評価実験において、腱
の連続性異常や感染の疑いがある例が含まれたが、コン
トロールである比較例１の評価実験においてもほぼ同率
に生じているため、このような疑いが多孔性癒着防止材
の埋入による副作用とは考えられない。腱の連続性に異
常があるものや感染の疑いがある例を除き、膜が原因と
思われる明らかな炎症反応は見られなかった。従って、
本発明の癒着防止材は副作用がなく、安全性においても
優れたものである。In the evaluation experiments of Examples 1 and 2, there were cases where tendon continuity was abnormal or infection was suspected, but in the evaluation experiment of Comparative Example 1 which was a control, almost the same rate occurred. Therefore, such suspicion is not considered to be a side effect due to the implantation of the porous adhesion preventing material. Except for those with abnormal tendon continuity or suspected infection, there was no apparent inflammatory response attributed to the membrane. Therefore,
The adhesion preventing material of the present invention has no side effects and is excellent in safety.
【００４５】（実施例３）Ｌ−乳酸とε−カプロラクト
ンとの共重合体（Ｍｗ４０万、乳酸とカプロラクトンと
の共重合体中における重量比：乳酸／カプロラクトン＝
５５／４５）の６重量％ジオキサン溶液をガラス板上に
キャストし、そのガラス板を−１３５℃の冷凍庫内に投
入して、前記溶液を凍結した。その後、凍結乾燥器で溶
剤（ジオキサン）を除去することにより、平均孔径１０
μｍ、空隙率８８％、厚み２００μｍの多孔質膜を得
た。そして、分子量約２２０万のヒアルロン酸粉末（紀
文社製）を０．５重量％の濃度になるように生理食塩水
に添加して、オートクレーブにより溶解させたヒアルロ
ン酸水溶液（以下同じ）に前記多孔質膜を浸漬し、これ
を凍結乾燥させた。このヒアルロン酸を含有する多孔質
膜を多孔性癒着防止材として用い、計１８例の損傷サン
プルについて癒着防止効果の評価を行なった。前記癒着
防止効果の評価は、第３趾の中央部の皮膚を約１５ｍｍ
切開したこと、長さ１５ｍｍ、幅１５ｍｍの前記癒着防
止材を使用したこと以外は、前記実施例１と同様にして
行なった。Example 3 Copolymer of L-lactic acid and ε-caprolactone (Mw 400,000, weight ratio in copolymer of lactic acid and caprolactone: lactic acid / caprolactone =
A 55% / 45% by weight dioxane solution was cast on a glass plate, and the glass plate was placed in a -135 ° C freezer to freeze the solution. Thereafter, the solvent (dioxane) was removed with a freeze dryer to obtain an average pore size of 10%.
A porous membrane having a thickness of 200 μm, a porosity of 88%, and a thickness of 200 μm was obtained. Then, hyaluronic acid powder having a molecular weight of about 2.2 million (manufactured by Kibunsha Co., Ltd.) was added to physiological saline to a concentration of 0.5% by weight, and the solution was added to a hyaluronic acid aqueous solution (hereinafter the same) dissolved in an autoclave. The membrane was soaked and lyophilized. Using this porous membrane containing hyaluronic acid as a porous anti-adhesion material, an anti-adhesion effect was evaluated for a total of 18 damaged samples. The evaluation of the adhesion prevention effect was performed by measuring the skin at the center of the third toe by about 15 mm.
The procedure was performed in the same manner as in Example 1 except that the incision was made and the adhesion preventing material having a length of 15 mm and a width of 15 mm was used.
【００４６】（実施例４）前記実施例３と同様にして、
平均孔径１０μｍ、空隙率８８％、厚み２００μｍの多
孔質膜を作製した。これを、損傷部に接する腱に巻き付
け、前記多孔質膜同士を融着固定した後、前記多孔質膜
にヒアルロン酸ナトリウム製剤（関節内注射液アルツ、
分子量約６０万〜１２０万、濃度１重量％、科研製薬社
製：以下同じ）を注入したものを多孔性癒着防止材とし
た以外は、前記実施例３と同様にして、計２例の損傷サ
ンプルについて、癒着防止効果の評価を行なった。(Example 4) In the same manner as in Example 3,
A porous membrane having an average pore diameter of 10 μm, a porosity of 88%, and a thickness of 200 μm was produced. This is wrapped around a tendon in contact with the injured portion, and the porous membranes are fused and fixed to each other. Then, the sodium hyaluronate preparation (articular intra-articular injection solution,
A total of two cases of damage were carried out in the same manner as in Example 3 except that a porous adhesion-preventing material was used, which had a molecular weight of about 600,000 to 1.2 million, a concentration of 1% by weight, and manufactured by Kaken Pharmaceutical Co., Ltd .; The samples were evaluated for adhesion prevention effects.
【００４７】（実施例５）前記ヒアルロン酸ナトリウム
製剤の代りに、前記実施例３と同様の０．５重量％ヒア
ルロン酸水溶液を用いた以外は、前記実施例４と同様に
して、計１７例の損傷サンプルについて、癒着防止効果
の評価を行なった。Example 5 A total of 17 examples were prepared in the same manner as in Example 4 except that the 0.5% by weight aqueous solution of hyaluronic acid used in Example 3 was used instead of the sodium hyaluronate preparation. The anti-adhesion effect of the damaged sample was evaluated.
【００４８】実施例３〜５における癒着スコア平均値は
それぞれ、実施例３が１．８点、実施例４が１．０点、
実施例５が１．５点であった。これより、本発明の多孔
性癒着防止材がさらにヒアルロン酸を含有することによ
って、一層癒着防止効果が向上することがわかる。The average values of the adhesion scores in Examples 3 to 5 were 1.8 in Example 3, 1.0 in Example 4, and 1.0 respectively.
Example 5 had 1.5 points. From this, it is understood that the adhesion preventing effect is further improved when the porous adhesion preventing material of the present invention further contains hyaluronic acid.
【００４９】（実施例６および比較例３）本発明の多孔
性癒着防止材を用いて、指屈曲機能回復効果の評価およ
び病理組織学的評価を行なった。使用した多孔性癒着防
止材および評価の方法を以下に示す。(Example 6 and Comparative Example 3) Using the porous anti-adhesion material of the present invention, the effect of restoring the finger flexing function and the histopathological evaluation were evaluated. The porous adhesion preventing material used and the evaluation method are shown below.
【００５０】（多孔性癒着防止材） （１）ＬＬＡ／ＣＬ 実施例１と同様にして作製した厚み２００μｍ、平均孔
径１０μｍ、空隙率８８％の多孔質膜を多孔性癒着防止
材（以下、「ＬＬＡ／ＣＬ」という）として用いた。 （２）ＨＡ−ＬＬＡ／ＣＬ 実施例３と同様にして作製した厚み２００μｍ、平均孔
径１０μｍ、空隙率８８％のヒアルロン酸含有多孔質膜
を多孔性癒着防止材（以下、「ＨＡ−ＬＬＡ／ＣＬ」と
いう）として用いた。 （３）ＬＬＡ／ＣＬ＋ＨＡ 実施例３と同様にして作製した厚み２００μｍ、平均孔
径１０μｍ、空隙率８８％の多孔質膜を、以下に示す損
傷部と接する腱に巻き付け、融着固定した後に、実施例
５と同様にして前記ヒアルロン酸水溶液を注入し、これ
を多孔性癒着防止材（以下、「ＬＬＡ／ＣＬ＋ＨＡ」と
いう）とした。(Porous Adhesion Preventing Material) (1) LLA / CL A porous film having a thickness of 200 μm, an average pore diameter of 10 μm, and a porosity of 88% produced in the same manner as in Example 1 was used as a porous anti-adhesion material (hereinafter, referred to as “A”). LLA / CL "). (2) HA-LLA / CL A hyaluronic acid-containing porous membrane having a thickness of 200 μm, an average pore diameter of 10 μm, and a porosity of 88% produced in the same manner as in Example 3 was coated with a porous anti-adhesion material (hereinafter, “HA-LLA / CL”). "). (3) LLA / CL + HA A porous membrane having a thickness of 200 μm, an average pore diameter of 10 μm, and a porosity of 88% produced in the same manner as in Example 3 was wound around a tendon in contact with the damaged part shown below, and then fixed by fusion. The hyaluronic acid aqueous solution was injected in the same manner as in Example 5, and this was used as a porous adhesion preventive material (hereinafter, referred to as “LLA / CL + HA”).
【００５１】（指屈曲機能回復効果の評価方法）体重
１．６〜１．８ｋｇの範囲であるニワトリ（赤玉鶏もみ
じ、５月齢）を用い、その第３趾の中央部の皮膚を約２
２ｍｍ切開した後、腱鞘を切開して前記腱鞘中の深趾屈
筋腱を露出させた。そして、切開部中央約７ｍｍの部分
にある腱周辺組織にバイポーラ電気メスで熱傷を与え、
損傷部とした。前記損傷部と接する腱部分に、長さ２２
ｍｍ、幅１５ｍｍの多孔性癒着防止材を巻き付けてか
ら、バイポーラ電気メスにより前記癒着防止材同士を融
着固定し、余分な材料は切除した。次に、５−０ナイロ
ン糸で切開部を縫合し、術後３週間は指伸展位にてギプ
ス固定を行なった。(Evaluation method of the effect of restoring the finger flexing function) Using a chicken (Akadama maple, 5 months old) weighing 1.6 to 1.8 kg, the skin at the center of the third toe was reduced by about 2 mm.
After 2 mm incision, the tendon sheath was incised to expose the flexor digital tendon in the tendon sheath. Then, the tissue around the tendon in the center of the incision about 7 mm is burned with a bipolar electric scalpel,
Damaged part. At the tendon part in contact with the damaged part, length 22
After winding a porous anti-adhesion material having a width of 15 mm and a width of 15 mm, the anti-adhesion materials were fused and fixed to each other with a bipolar electric knife, and excess material was cut off. Next, the incision was sutured with 5-0 nylon thread, and cast was fixed at the finger extension position for 3 weeks after the operation.
【００５２】前記癒着防止材を埋入してから３週間後
に、ジエチルエーテルを大量吸入させてニワトリを犠牲
死させ、手術した指の付け根部分を切断し、前記付け根
から約５ｍｍの深趾屈筋腱だけを露出させた。これを引
張り試験機（製品名ＡＧＳ−５Ｄ：島津製作所社製）の
治具に取り付けてから、前記治具を前記引張り試験機に
セットした。そして、前記引張り試験機のチャックに前
記深趾屈筋腱を挟み、引張り強度１０ｍｍ／分、最大荷
重５００ｇｆの条件で引張り試験を行ない、同時にこれ
をビデオカメラで撮影した。Three weeks after embedding the adhesion preventing material, the chicken was sacrificed by inhaling a large amount of diethyl ether, and the root of the operated finger was cut off. Only exposed. This was mounted on a jig of a tensile tester (product name: AGS-5D: manufactured by Shimadzu Corporation), and then the jig was set on the tensile tester. Then, the flexor toe flexor tendon was sandwiched between chucks of the tensile tester, and a tensile test was performed under the conditions of a tensile strength of 10 mm / min and a maximum load of 500 gf, and at the same time, this was photographed with a video camera.
【００５３】そして、測定結果から荷重が５００ｇｆに
達するのに要した時間を割り出し、録画したビデオテー
プから、その時間における指の屈折角を分度器で計測す
ることにより、荷重５００ｇｆで前記深趾屈筋腱を引張
った時の指の屈曲率：Totalangle motion（ＴＡＭ）を
求めた。Then, the time required for the load to reach 500 gf was determined from the measurement result, and the refraction angle of the finger at that time was measured from the recorded videotape with a protractor. Of the finger when the finger was pulled: Total angle motion (TAM) was determined.
【００５４】ＬＬＡ／ＣＬ、ＨＡ−ＬＬＡ／ＣＡおよび
ＬＬＡ／ＣＬ＋ＨＡに対し、それぞれ計８例の損傷サン
プルについての評価を行ない、これらの平均を求めた。
また、比較例３は、損傷部に処理を行なわずにそのまま
閉創した以外は、前述と同様にして操作を行ない、計３
７例の損傷サンプルについての評価の平均を求めた。こ
れらの結果を下記表１に示す。Evaluation was performed on a total of eight damaged samples for each of LLA / CL, HA-LLA / CA and LLA / CL + HA, and the average thereof was determined.
In Comparative Example 3, an operation was performed in the same manner as described above, except that the wound was directly closed without performing any processing.
The average of the evaluations for the seven damaged samples was determined. The results are shown in Table 1 below.
【００５５】（病理組織学的検査）前記指屈曲機能回復
効果の評価方法と同様にして、損傷部に多孔性癒着防止
材を３週間埋入させた後、図１に示すように、前記多孔
性癒着防止材の埋入部中心３、前記埋入部の端部２、
４、埋入部周囲の非埋入部１、５における腱の断面組織
を切り出した。なお、同図において、矢印（Ｐｒｏｘｉ
ｍａｌ）は、体の中心方向を示し、矢印（Ｄｉｓｔａ
ｌ）は、末端方向を示す。これらの組織切片を１０重量
％中性ホルマリン溶液により固定した後、プランクリュ
クロ法により脱灰し、水溶性パラフィン包理液を用いて
包理した。これを厚み約１０μｍに切り取り、ヘマトキ
シリン−エオシン（ＨＥ）染色により染色したものをガ
ラススライドに封入した後、光学顕微鏡（４００倍）で
観察し、円形（直径０．１７８ｍｍ、０．０２５ｍ
ｍ2）内の細胞核数を測定した。そして、各切片の任意
の３箇所について測定を行ない、その平均細胞核数を求
めた。なお、コントロールとして、未処理の深趾屈筋腱
を使用し、水溶性パラフィン包理液の代りにキシレン含
有パラフィン包理液を用いた以外は、同様にして測定を
行なった。これらの結果を図２のグラフに示す。図２に
おいて、縦軸は腱の細胞核数を示し、横軸の数字は腱の
切片部位、ａはＬＬＡ／ＣＬ、ｂはＬＬＡ／ＣＬ＋Ｈ
Ａ、ｃはＨＡ−ＬＬＡ／ＣＬ、ｄはコントロールを示
す。(Histopathological Examination) In the same manner as in the above-mentioned method of evaluating the effect of restoring the finger bending function, a porous adhesion preventive material was embedded in the damaged portion for 3 weeks, and as shown in FIG. Center 3 of the embedded portion of the anti-adhesive material, end 2 of the embedded portion,
4. The cross-sectional tissue of the tendon in the non-implanted portions 1 and 5 around the implanted portion was cut out. Note that, in FIG.
mal) indicates the center direction of the body, and an arrow (Dista)
l) indicates the terminal direction. After fixing these tissue sections with a 10% by weight neutral formalin solution, the tissues were decalcified by the plan-cruchro method and embedded with a water-soluble paraffin embedding solution. This was cut into a thickness of about 10 μm, stained with hematoxylin-eosin (HE), sealed in a glass slide, observed with an optical microscope (× 400), and circular (diameter: 0.178 mm, 0.025 m).
The number of cell nuclei in m 2 ) was determined. Then, measurement was performed at three arbitrary points on each section, and the average number of cell nuclei was determined. As a control, the measurement was performed in the same manner except that an untreated flexor tendon muscle tendon was used and a paraffin-embedded solution containing xylene was used instead of the water-soluble paraffin-embedded solution. These results are shown in the graph of FIG. In FIG. 2, the ordinate indicates the number of cell nuclei in the tendon, the number on the abscissa indicates the section of the tendon, a indicates LLA / CL, and b indicates LLA / CL + H.
A and c indicate HA-LLA / CL, and d indicates a control.
【００５６】[0056]
【表１】 サンプル数 ＴＡＭ（平均値±ＳＤ） 実施例６ （１）ＬＬＡ／ＣＬ ８ １６±１０ （２）ＨＡ−ＬＬＡ／ＣＡ ８ ２７±２８ （３）ＬＬＡ／ＣＬ＋ＨＡ ８ ５９±５４比較例３ ３７ １２±２２ ＳＤ：標準偏差Table 1 Number of Samples TAM (Average ± SD) Example 6 (1) LLA / CL 8 16 ± 10 (2) HA-LLA / CA 8 27 ± 28 (3) LLA / CL + HA 8 59 ± 54 Comparative Example 337 12 ± 22 SD: standard deviation
【００５７】前記表１に示すように、実施例６の各多孔
性癒着防止材は、比較例に比べて、優れた屈曲角を示
し、特に、多孔質膜にヒアルロン酸を注入した多孔質性
癒着防止材（ＬＬＡ／ＣＬ＋ＨＡ）は、最も優れた屈曲
率を示した。前述のように、前記多孔質膜にヒアルロン
酸を含有させることにより、腱と腱周辺組織との癒着が
さらに防止されるため、指の屈曲機能もより回復される
といえる。As shown in Table 1, each of the porous adhesion preventive materials of Example 6 exhibited an excellent bending angle as compared with the comparative example, and in particular, the porous film obtained by injecting hyaluronic acid into the porous film was used. The anti-adhesion material (LLA / CL + HA) showed the best bending rate. As described above, by including hyaluronic acid in the porous membrane, adhesion between the tendon and the tissue surrounding the tendon is further prevented, so that it can be said that the bending function of the finger is further restored.
【００５８】また、本発明の多孔性癒着防止材を用いれ
ば、前述のように、腱周辺の癒着を防止することができ
るが、腱を周辺組織から覆うことにより、外部から物資
が補給されにくく、治癒が遅くなるというおそれがあっ
た。このため、図２に示すように、本発明の多孔性癒着
防止材（ＬＬＡ／ＣＬ）ａを用いた場合、コントロール
ｄに比べて、特に損傷部と接する腱（図１の断面３）に
おいて、細胞核が減少するという傾向が見られていた。
しかしながら、図２に示すように、前記多孔質膜にヒア
ルロン酸を含有させたＬＬＡ／ＣＬ＋ＨＡ（ｂ）および
ＨＡ−ＬＬＡ／ＣＬ（ｃ）によれば、細胞核の減少が抑
制されたことがわかる。Further, the use of the porous anti-adhesion material of the present invention can prevent the adhesion around the tendon, as described above. However, by covering the tendon from the surrounding tissue, it is difficult to supply materials from the outside. However, there is a fear that healing is delayed. For this reason, as shown in FIG. 2, when the porous adhesion preventing material (LLA / CL) a of the present invention is used, especially in the tendon (cross section 3 in FIG. 1) in contact with the damaged part, compared to the control d. There was a tendency for cell nuclei to decrease.
However, as shown in FIG. 2, according to LLA / CL + HA (b) and HA-LLA / CL (c) in which the porous membrane contained hyaluronic acid, it was found that the reduction of cell nuclei was suppressed.
【００５９】このように、本発明の多孔性癒着防止材が
ヒアルロン酸を含有することにより、腱と腱周辺部位と
の癒着がより一層防止されるだけではなく、屈曲機能の
回復にも優れた効果を示し、腱組織の壊死も抑制するこ
とができた。As described above, since the porous anti-adhesion material of the present invention contains hyaluronic acid, not only the adhesion between the tendon and the site around the tendon can be further prevented, but the recovery of the bending function is excellent. It showed an effect and was able to suppress the necrosis of tendon tissue.
【００６０】[0060]
【発明の効果】本発明の多孔性癒着防止材は、腱と周辺
組織とを物理的に隔離することができるため、腱の癒着
を効果的に防止することができる。また、適度な柔軟性
を持つため、操作性に優れる。また、多孔性膜であるた
め、栄養物質の透過性に優れ、腱の癒合を阻害しない。
また、生体吸収性に優れ、さらに、生体にとって副作用
が少なく、安全性においても優れる。As described above, the porous adhesion preventing material of the present invention can physically separate the tendon from the surrounding tissue, thereby effectively preventing the adhesion of the tendon. In addition, since it has moderate flexibility, it is excellent in operability. Moreover, since it is a porous membrane, it is excellent in the permeability of nutrient substances and does not inhibit the healing of tendons.
In addition, it is excellent in bioabsorbability, has few side effects on living organisms, and is excellent in safety.
【図１】本発明の多孔性癒着防止材の一実施例におけ
る、損傷サンプルの切断部位を示す模式図である。FIG. 1 is a schematic view showing a cut portion of a damaged sample in one embodiment of the porous adhesion preventing material of the present invention.
【図２】前記実施例において、多孔性癒着防止材を用い
て腱の各部位における細胞核数を測定した結果を示すグ
ラフである。FIG. 2 is a graph showing the results of measuring the number of cell nuclei at each site of a tendon using the porous adhesion preventing material in the above example.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 山内 康治 京都府綾部市青野町棗ヶ市46番地 グンゼ 株式会社研究開発部内 (72)発明者 富田 直秀 三重県名張市木屋町814 町井方 (72)発明者 岩田 博夫 大阪府三島郡島本町若山台１丁目５番地８ −203 (72)発明者 筏 義人 京都府宇治市五ケ庄広岡谷２番地182 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Koji Yamauchi 46, Natsuga-shi, Aono-cho, Ayabe-shi, Kyoto Gunze R & D Dept. Inventor Hiroo Iwata 1-5-8 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka Prefecture -203 (72) Inventor Yoshito Raft 2-182 Gokasho Hirookadani, Uji City, Kyoto Prefecture
Claims (9)
なる多孔性癒着防止材。1. A porous anti-adhesion material comprising a copolymer of lactic acid and caprolactone.
０〜５００，０００である請求項１に記載の多孔性癒着
防止材。2. A copolymer having a weight average molecular weight of 50,000.
The porous adhesion preventing material according to claim 1, wherein the amount is from 0 to 500,000.
共重合割合が重量比で乳酸／カプロラクトン＝８０／２
０〜３０／７０である請求項１又は２に記載の多孔性癒
着防止材。3. The copolymerization ratio of lactic acid and caprolactone in the copolymer is lactic acid / caprolactone = 80/2 by weight.
The porous adhesion preventing material according to claim 1, wherein the ratio is 0 to 30/70.
る請求項１〜３のいずれか１項に記載の多孔性癒着防止
材。4. The porous adhesion-preventing material according to claim 1, wherein the average pore size of the pores is 0.1 to 80 μm.
る請求項４に記載の多孔性癒着防止材。5. The porous anti-adhesion material according to claim 4, wherein the average pore diameter of the pores is 0.5 to 50 μm.
５のいずれか１項に記載の多孔性癒着防止材。6. A porosity of 40 to 95%.
6. The porous adhesion preventing material according to any one of items 5 to 5.
〜６のいずれか１項に記載の多孔質性癒着防止材7. The method according to claim 1, further comprising hyaluronic acid.
The porous adhesion preventive material according to any one of Items 1 to 6,
材全体の０．１〜１０重量％の範囲である請求項１〜７
のいずれか１項に記載の多孔性癒着防止材。8. The method according to claim 1, wherein the content of hyaluronic acid is in the range of 0.1 to 10% by weight of the whole porous adhesion preventing material.
The porous adhesion preventing material according to any one of the above.
ために用いられる請求項１〜８のいずれか１項に記載の
多孔性癒着防止材。9. The porous anti-adhesive material according to claim 1, which is used for preventing tendon adhesion in treating tendon damage.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28548999A JP4405003B2 (en) | 1998-10-19 | 1999-10-06 | Porous anti-adhesive material |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29672298 | 1998-10-19 | ||
| JP10-296722 | 1998-10-19 | ||
| JP28548999A JP4405003B2 (en) | 1998-10-19 | 1999-10-06 | Porous anti-adhesive material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000197693A true JP2000197693A (en) | 2000-07-18 |
| JP4405003B2 JP4405003B2 (en) | 2010-01-27 |
Family
ID=26555914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28548999A Expired - Lifetime JP4405003B2 (en) | 1998-10-19 | 1999-10-06 | Porous anti-adhesive material |
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| Country | Link |
|---|---|
| JP (1) | JP4405003B2 (en) |
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| JP2008272453A (en) * | 2007-03-30 | 2008-11-13 | Jms Co Ltd | Process for production of porous body and uses thereof |
| JP2013226410A (en) * | 2012-03-29 | 2013-11-07 | Jms Co Ltd | Composite of lactide-caprolactone copolymer film and method for manufacturing the same |
| JP2014200199A (en) * | 2013-04-05 | 2014-10-27 | 株式会社ダイセル | Biocompatible porous body and manufacturing method of the same |
| JP2018089370A (en) * | 2016-12-05 | 2018-06-14 | グンゼ株式会社 | Nerve anti-conglutinate wrapping material |
| WO2023134146A1 (en) * | 2022-01-11 | 2023-07-20 | 长春圣博玛生物材料有限公司 | Use of lactic acid in product for regulating and promoting tissue growth |
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