JP3517358B2 - Anti-adhesion material and method for producing the same - Google Patents
Anti-adhesion material and method for producing the sameInfo
- Publication number
- JP3517358B2 JP3517358B2 JP20564698A JP20564698A JP3517358B2 JP 3517358 B2 JP3517358 B2 JP 3517358B2 JP 20564698 A JP20564698 A JP 20564698A JP 20564698 A JP20564698 A JP 20564698A JP 3517358 B2 JP3517358 B2 JP 3517358B2
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- Prior art keywords
- adhesion
- gelatin
- material according
- film
- sponge
- Prior art date
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Description
【０００１】[0001]
【発明の属する技術分野】本発明は、生体組織同士の癒
着を防止する癒着防止材及びその製造方法に関する。TECHNICAL FIELD The present invention relates to an adhesion preventing material for preventing adhesion between living tissues and a method for producing the same.
【０００２】[0002]
【従来の技術】外科手術後には、しばしば生体組織同士
の癒着が発生し、痛みや機能障害を引き起こすが、癒着
は産婦人科、消化器外科、整形外科および心臓外科分野
においてとくに問題となり、ひどい場合は癒着を剥離す
るための手術が必要になる。また、癒着のため、原疾患
の再手術が困難であることが多い。この癒着を防止する
ために、癒着の発生する恐れのある部位を膜で隔離する
方法があり、一部で使用されている。BACKGROUND OF THE INVENTION After surgery, adhesion between living tissues often occurs, causing pain and dysfunction. Adhesion is a serious problem in the fields of obstetrics and gynecology, gastroenterological surgery, orthopedic surgery and cardiac surgery, and is terrible. You may need surgery to remove the adhesion. Also, because of adhesions, it is often difficult to re-operate the original disease. In order to prevent this adhesion, there is a method of isolating a site where adhesion may occur with a membrane, which is used in part.
【０００３】[0003]
【発明が解決しようとする課題】このような癒着防止法
に現在使用されている材料としては、酸化セルロース膜
やヒアルロン酸・カルボキシメチルセルロース混合膜が
あるが、その効果は極めて不充分で、限られた症例に使
用されているにすぎない。本発明者らは、酸化セルロー
ス膜の癒着防止効果が不充分な理由について種々検討を
行った結果、以下に述べる２つ問題点があることが判明
した。すなわち、第１の問題点は、膜が生体に充分に固
定されず、当初の位置から動いてしまうことである。そ
のため、癒着防止が必要な部位で遮蔽効果が発揮されな
いことになる。これに対して、膜を確実に固定する方法
として接着剤による接着や縫合糸による縫合が考えられ
るが、酸化セルロース膜は強度が弱いために、これらの
方法で固定するのは困難である。また、たとえこのよう
な方法で固定できたとしても、そのような固定処置自体
が逆に癒着を惹起したり促進する可能性があることが、
本発明者らの検討で明らかになった。したがって、優れ
た癒着防止効果を得るためには、生体組織に貼付するだ
けで確実かつ容易に固定できることが必要である。次に
第２の問題は、酸化セルロース膜を生体内に挿入する
と、短時間で形態が崩れて消失し、必要な期間遮蔽効果
を維持できなくなることである。したがって、酸化セル
ロース膜よりも長期間形態を維持できることが必要であ
り、数日間程度は形態を保持しその後は速やかに吸収さ
れる材料が好ましいと考えられる。[Problems that the Invention is to Solve As a material that is currently used for such anti-adhesion method, it is oxidized cellulose film and hyaluronic acid carboxyl caulking chill cellulose mixed film, the effect is quite insufficient, It is only used in a limited number of cases. As a result of various studies on the reason why the adhesion preventing effect of the oxidized cellulose film is insufficient, the present inventors have found that there are two problems described below. That is, the first problem is that the membrane is not sufficiently fixed to the living body and moves from the initial position. Therefore, the shielding effect is not exerted at the site where adhesion prevention is required. On the other hand, as a method for securely fixing the membrane, adhesion with an adhesive or suturing with a suture thread is conceivable, but it is difficult to fix the oxidized cellulose membrane by these methods because of its weak strength. In addition, even if it can be fixed by such a method, there is a possibility that such fixing treatment itself may cause or promote adhesion.
It became clear by the examination of the present inventors. Therefore, in order to obtain an excellent anti-adhesion effect, it is necessary to be able to surely and easily fix the body tissue only by attaching it. Next, the second problem is that when the oxidized cellulose membrane is inserted into the living body, the shape is lost and disappears, and the shielding effect cannot be maintained for a necessary period. Therefore, it is necessary that the morphology can be maintained for a longer period of time than the oxidized cellulose membrane, and it is considered that a material that retains the morphology for several days and is quickly absorbed thereafter is preferable.
【０００４】尚、化学的（ホルムアルデヒド）に架橋さ
れたゼラチン製癒着防止膜が、アップジョン（ＵＰＪＯ
ＨＮ）社よりＧｅｌ ｆｉｌｍ（登録商標）として市販
されているが、この膜は生体内での分解吸収時間が長
く、また生体内での移動や異物反応の点で有用なものと
はいえなかった。An adhesion preventive film made of gelatin that is chemically (formaldehyde) crosslinked is known as UPJO.
It is marketed as Gel film (registered trademark) by HN), but this membrane was not useful in terms of long degradation and absorption time in vivo and migration and foreign body reaction in vivo. .
【０００５】本発明の目的は、このような機能を持った
癒着防止材を提供することにある。すなわち、生体組織
に確実かつ容易に固定できるようにするために、生体に
対して適度な接着性を持ち、生体組織に簡単に貼付で
き、かつ、数日程度の期間は生体内で形態を保持し、そ
の後は速やかに生体に吸収される癒着防止材を提供する
ことにある。さらに他の目的は、そのような癒着防止材
の製造方法を提供することにある。An object of the present invention is to provide an adhesion preventive material having such a function. In other words, in order to be able to securely and easily fix it to the living tissue, it has appropriate adhesiveness to the living body, can be easily attached to the living tissue, and retains its form in the living body for a period of about several days. However, the object of the present invention is to provide an adhesion preventive material that is quickly absorbed by the living body. Still another object is to provide a method for producing such an adhesion preventive material.
【０００６】[0006]
【課題を解決するための手段】前記目的を達成するため
に、本発明の癒着防止材は、所定形状に成形したゼラチ
ンに、１５Ｗの紫外線を、照射距離６０ｃｍで５〜１５
時間照射して架橋した架橋ゼラチンを含む癒着防止材で
ある。前記ゼラチンは、グリセリンを含むことが好まし
い。前記癒着防止材は、形態がスポンジ状であってもよ
く、スポンジの孔径は５μｍ以下が好ましく、厚みは、
５０〜５００μｍの範囲が好ましい。前記癒着防止材
は、形態がフィルム状であってもよく、厚みは１０〜３
００μｍであることが好ましい。In order to achieve the above object, the anti-adhesion material of the present invention comprises gelatin molded into a predetermined shape and 5 W of ultraviolet rays of 15 W at an irradiation distance of 60 cm.
It is an anti-adhesion material containing cross-linked gelatin cross-linked by irradiation for a time. The gelatin preferably contains glycerin. The anti-adhesion material may have a sponge-like form, and the pore diameter of the sponge is preferably 5 μm or less, and the thickness is
The range of 50 to 500 μm is preferable. The adhesion preventive material may be in the form of a film and has a thickness of 10 to 3
It is preferably 00 μm.
【０００７】また、本発明のその他の癒着防止材は、ゼ
ラチンを含む癒着防止材であって、前記ゼラチン紫外線
照射により架橋しており、前記ゼラチンのグルコース拡
散係数が、４×１０−６〜１×１０−５ｃｍ２／ｓであ
る癒着防止材である。前記ゼラチンは、グリセリンを含
むことが好ましい。前記癒着防止材は、形態がスポンジ
状であってもよく、スポンジの孔径は５μｍ以下が好ま
しく、厚みは、５０〜５００μｍの範囲が好ましい。前
記癒着防止材は、形態がフィルム状であってもよく、厚
みは１０〜３００μｍであることが好ましい。前記紫外
線の照射条件は、例えば、１５Ｗの紫外線を、照射距離
６０ｃｍで５〜１５時間照射するという条件である。Further, another adhesion preventive material of the present invention is an adhesion preventive material containing gelatin, which is cross-linked by irradiation of the gelatin ultraviolet ray, and the glucose diffusion coefficient of the gelatin is 4 × 10 -6 to 1. It is an anti-adhesion material having a density of × 10 −5 cm 2 / s. The gelatin preferably contains glycerin. The anti-adhesion material may have a sponge shape, and the pore diameter of the sponge is preferably 5 μm or less, and the thickness is preferably in the range of 50 to 500 μm. The adhesion preventing material may be in the form of a film, and the thickness thereof is preferably 10 to 300 μm. The irradiation condition of the ultraviolet ray is, for example, a condition that the ultraviolet ray of 15 W is irradiated for 5 to 15 hours at an irradiation distance of 60 cm.
【０００８】本発明のさらにその他の癒着防止材は、ゼ
ラチンを含む癒着防止材であって、前記ゼラチン紫外線
照射により架橋しており、前記ゼラチンの含水率が８５
〜９５重量％の範囲である癒着防止材である。前記ゼラ
チンは、グリセリンを含むことが好ましい。前記癒着防
止材は、形態がスポンジ状であってもよく、スポンジの
孔径は５μｍ以下が好ましく、厚みは、５０〜５００μ
ｍの範囲が好ましい。前記癒着防止材は、形態がフィル
ム状であってもよく、厚みは１０〜３００μｍであるこ
とが好ましい。前記ゼラチンのグルコース拡散係数は、
４×１０−６〜１×１０−５ｃｍ２／ｓであることが好
ましい。前記紫外線の照射条件は、例えば、１５Ｗの紫
外線を、照射距離６０ｃｍで５〜１５時間照射するとい
う条件である。Yet another adhesion preventive material of the present invention is an adhesion preventive material containing gelatin, which is cross-linked by irradiation of the gelatin ultraviolet ray and has a water content of 85.
The anti-adhesion material is in the range of ˜95% by weight. The gelatin preferably contains glycerin. The anti-adhesion material may have a sponge-like shape, and the pore diameter of the sponge is preferably 5 μm or less and the thickness is 50 to 500 μm.
A range of m is preferred. The adhesion preventing material may be in the form of a film, and the thickness thereof is preferably 10 to 300 μm. The glucose diffusion coefficient of the gelatin is
It is preferably 4 × 10 −6 to 1 × 10 −5 cm 2 / s. The irradiation condition of the ultraviolet ray is, for example, a condition that the ultraviolet ray of 15 W is irradiated for 5 to 15 hours at an irradiation distance of 60 cm.
【０００９】本発明のさらにその他の癒着防止材は、所
定形状に成形したゼラチンを、１２０〜１７０℃の温度
で熱処理をすることによりに架橋した架橋ゼラチンを含
む癒着防止材である。前記ゼラチンは、グリセリンを含
むことが好ましい。前記癒着防止材は、形態がスポンジ
状であってもよく、スポンジの孔径は５μｍ以下が好ま
しく、厚みは、５０〜５００μｍの範囲が好ましい。前
記癒着防止材は、形態がフィルム状であってもよく、厚
みは１０〜３００μｍであることが好ましい。前記架橋
ゼラチンの含水率は、８５〜９５重量％の範囲にあるこ
とが好ましい。前記架橋ゼラチンのグルコース拡散係数
が、４×１０−６〜１×１０−５ｃｍ２／ｓであること
が好ましい。Still another adhesion preventive material of the present invention is an adhesion preventive material containing cross-linked gelatin obtained by cross-linking gelatin formed into a predetermined shape by heat treatment at a temperature of 120 to 170 ° C. The gelatin preferably contains glycerin. The anti-adhesion material may have a sponge shape, and the pore diameter of the sponge is preferably 5 μm or less, and the thickness is preferably in the range of 50 to 500 μm. The adhesion preventing material may be in the form of a film, and the thickness thereof is preferably 10 to 300 μm. The water content of the crosslinked gelatin is preferably in the range of 85 to 95% by weight. The glucose diffusion coefficient of the crosslinked gelatin is preferably 4 × 10 −6 to 1 × 10 −5 cm 2 / s.
【００１０】本発明の癒着防止材の製造方法は、架橋ゼ
ラチンを含む癒着防止材の製造方法であって、ゼラチン
を所定形状に成形した後、１５Ｗの紫外線を、照射距離
６０ｃｍで５〜１５時間照射することによりゼラチン内
の分子を架橋させる製造方法である。The method for producing an anti-adhesion material of the present invention is a method for producing an anti-adhesion material containing cross-linked gelatin, which comprises molding gelatin into a predetermined shape and then applying 15 W of ultraviolet light at an irradiation distance of 60 cm for 5 to 15 hours. This is a manufacturing method in which molecules in gelatin are crosslinked by irradiation.
【００１１】本発明の癒着防止材の製造方法は、架橋ゼ
ラチンを含む癒着防止材の製造方法であって、ゼラチン
を所定形状に成形した後、１２０〜１７０℃の温度で熱
処理することによりゼラチン内の分子を架橋させる製造
方法である。The method for producing an anti-adhesion material of the present invention is a method for producing an anti-adhesion material containing cross-linked gelatin. This is a manufacturing method for crosslinking the molecule.
【００１２】[0012]
【発明の実施の形態】本発明において使用するゼラチン
としては、通常市販されているゼラチンを使用すること
ができるが、食品用として供給されているものよりも医
療用に提供されているものの方が好ましく、パイロジェ
ンの含有量が少ないものが特に好ましい。BEST MODE FOR CARRYING OUT THE INVENTION As gelatin used in the present invention, gelatin which is usually commercially available can be used, but gelatin provided for medical use is more preferable than that supplied for food. Those having a low content of pyrogen are particularly preferable.
【００１３】ゼラチンの成形は、ゼラチンの成形法とし
て公知の方法により行なうことができる。例えばフィル
ム状に成形したい場合は、ゼラチンを水または有機溶媒
に溶解し、ガラス板等の平面上に流延して乾燥させれ
ば、フィルム状の成形物を得ることができる。或いは、
無機塩等の造孔剤をゼラチンに混入した後、造孔剤のみ
を溶解させたり、発泡化して凍結乾燥し、スポンジ状の
成形物を得ることもできる。さらに、上記を組み合わせ
てスポンジ状のシートを成形しても良い。The gelatin can be molded by a method known as a gelatin molding method. For example, when it is desired to form a film, a film-like molded product can be obtained by dissolving gelatin in water or an organic solvent, casting it on a flat surface such as a glass plate and drying it. Alternatively,
It is also possible to obtain a sponge-like molded product by mixing a pore-forming agent such as an inorganic salt with gelatin and then dissolving only the pore-forming agent or foaming and freeze-drying. Further, the above may be combined to form a sponge-like sheet.
【００１４】フィルム状の成形物を得た場合に、癒着防
止材としては、１０〜３００μｍの厚みのフィルムとす
ることが好ましい。５０〜１５０μｍの厚みのフィルム
がさらに好ましい。薄すぎると破れやすく、逆に厚すぎ
ると硬く、使いにくい。When a film-shaped molded product is obtained, the adhesion preventing material is preferably a film having a thickness of 10 to 300 μm. A film having a thickness of 50 to 150 μm is more preferable. If it is too thin, it will tear easily, and if it is too thick, it will be hard and difficult to use.
【００１５】スポンジ状の成形物を得た場合に、癒着防
止材としては、厚み５０〜５００μｍ、孔径５μｍ以下
とすることが好ましい。When a sponge-like molded article is obtained, the adhesion preventing material preferably has a thickness of 50 to 500 μm and a pore diameter of 5 μm or less.
【００１６】得られた成形物は、生体内に挿入すると生
体に吸収されるが、癒着防止材として使用するために
は、これよりもゆっくりと吸収される必要がある。本発
明においては、成形物に紫外線を照射することによりゼ
ラチンを架橋し、生体での分解吸収速度（以下、「吸収
速度」ともいう）を遅くする。後述する図１に示される
ように、吸収速度の低下、すなわち、生体での成形物の
残存の程度は、紫外線の照射量と相関があるので、目標
とする吸収速度になるように照射量を調節すれば良い。
例えば、吸収速度を遅くするために成形物に照射する紫
外線照射量を増加させることもできるし、逆に吸収速度
を速くするために紫外線照射量を減少させることもでき
る。The obtained molded product is absorbed into the living body when it is inserted into the living body, but it needs to be absorbed more slowly than this in order to be used as an adhesion preventing material. In the present invention, the gelatin is cross-linked by irradiating the molded product with ultraviolet rays to slow the rate of decomposition and absorption in the living body (hereinafter, also referred to as “absorption rate”). As shown in FIG. 1 which will be described later, the decrease in absorption rate, that is, the degree of remaining of the molded product in the living body has a correlation with the irradiation amount of ultraviolet rays. Just adjust it.
For example, it is possible to increase the ultraviolet ray irradiation amount for irradiating the molded article in order to reduce the absorption rate, and conversely, it is possible to decrease the ultraviolet ray irradiation amount in order to increase the absorption rate.
【００１７】紫外線照射量としては、特に限定されるも
のではないが、生体内での吸収分解性の点から、例えば
１５ワットの紫外線を６０ｃｍの距離で５〜１５時間照
射することが好ましい。紫外線の照射時間が５時間未満
の場合は、分解が速すぎるため、充分に損傷組織を隔離
できない。逆に１５時間を超えると、生体内での吸収分
解が遅くなり、異物反応を引き起こし、かえって癒着を
引き起こす。The irradiation amount of ultraviolet rays is not particularly limited, but from the viewpoint of absorption and decomposition in the living body, it is preferable to irradiate ultraviolet rays of, for example, 15 watts at a distance of 60 cm for 5 to 15 hours. When the irradiation time of ultraviolet rays is less than 5 hours, the decomposition is too fast to sufficiently isolate the damaged tissue. On the other hand, if it exceeds 15 hours, absorption and decomposition in the body will be delayed, causing a foreign body reaction and conversely causing adhesion.
【００１８】上記のように紫外線処理を行なったゼラチ
ンからなる本発明の癒着防止材は、含水率８５〜９５重
量％、グルコース拡散係数４×１０-6〜１×１０-5ｃｍ
2／ｓという性質を有する。The adhesion preventive material of the present invention comprising gelatin which has been subjected to the ultraviolet ray treatment as described above has a water content of 85 to 95% by weight and a glucose diffusion coefficient of 4 × 10 -6 to 1 × 10 -5 cm.
It has the property of 2 / s.
【００１９】含水率が９５重量％を超えると、分解吸収
時間が短くなる（消失が速いと癒着防止効果も低下す
る）。一方、含水率が８５重量％未満の場合は、柔軟性
が低下し、生体組織にフィットし難くなるため、癒着防
止効果が低下する。また、含水率が低い場合には、分解
吸収時間が長くなり、体内での滞留時間が長いと生体内
での異物反応が顕著になり、逆に癒着防止の効果は低下
する。When the water content exceeds 95% by weight, the decomposition and absorption time is shortened (the faster the disappearance, the lower the adhesion prevention effect). On the other hand, when the water content is less than 85% by weight, the flexibility is lowered and it becomes difficult to fit the living tissue, and thus the adhesion preventing effect is lowered. In addition, when the water content is low, the decomposition and absorption time becomes long, and when the residence time in the body is long, the foreign body reaction in the body becomes remarkable, and conversely the effect of preventing adhesion decreases.
【００２０】グルコース拡散係数が１×１０-5ｃｍ2／
ｓ を超えると、細胞浸潤や体液成分の透過が昂進し、
癒着防止効果が低下する。一方、グルコース拡散係数が
４×１０-6ｃｍ2／ｓ 未満の場合は、癒着防止を目的と
する生体部位への栄養透過が低下し、組織修復が遅くな
る。The glucose diffusion coefficient is 1 × 10 -5 cm 2 /
When it exceeds s, cell infiltration and permeation of body fluid components are accelerated,
The anti-adhesion effect is reduced. On the other hand, when the glucose diffusion coefficient is less than 4 × 10 −6 cm 2 / s, the nutrient transmission to the body part for the purpose of preventing adhesion is lowered and the tissue repair is delayed.
【００２１】また架橋の目的では、紫外線照射以外に熱
処理なども使用することができる。熱処理の温度として
は１２０〜１７０℃で処理するのが好ましい。For the purpose of crosslinking, heat treatment or the like can be used in addition to ultraviolet irradiation. The heat treatment temperature is preferably 120 to 170 ° C.
【００２２】フィルム状成形物を生体に密着しやすくす
るためには、優れた柔軟性を有することが好ましいが、
グリセリンを添加することにより、成形物の柔軟性を向
上することができる。グリセリンは、成形前にゼラチン
に混合し成形する。グリセリンの添加量は、ゼラチンに
対して５０重量％程度までが適当である。It is preferable that the film-shaped molded article has excellent flexibility in order to easily adhere to the living body.
By adding glycerin, the flexibility of the molded product can be improved. Glycerin is mixed with gelatin before molding and molded. An appropriate amount of glycerin added is about 50% by weight of gelatin.
【００２３】[0023]
【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、「部」は「重量部」であり、癒
着発生率以外の「％」は「重量％」である。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
In the following examples, "part" is "part by weight", and "%" other than the adhesion occurrence rate is "% by weight".
【００２４】［実施例１］ゼラチン（新田ゼラチン製Ｇ
０５４５Ｐ）を水に溶解して１０％水溶液を調製し、こ
れを撥水処理したガラス板上に流延して乾燥し、厚さ約
１００μｍのフィルムを得た。殺菌用の紫外線ランプ
（東芝（株）製、ＧＬ−１５）を使用して、得られたゼ
ラチンフィルムに１５ワットの紫外線を６０ｃｍの距離
で１０、２０、４０時間照射し（表と裏を半分の時間ず
つ）、以下の癒着防止効果の評価に使用した。尚、比較
品として市販の癒着防止材料も同様に評価に供した。ル
ムを得た。[Example 1] Gelatin (G manufactured by Nitta Gelatin
0545P) was dissolved in water to prepare a 10% aqueous solution, which was cast on a water-repellent treated glass plate and dried to obtain a film having a thickness of about 100 μm. Using a UV lamp for sterilization (GL-15, manufactured by Toshiba Corp.), the resulting gelatin film was irradiated with 15 watts of UV light at a distance of 60 cm for 10, 20, 40 hours (half the front and the other half). For each time), and used for the evaluation of the following adhesion prevention effect. As a comparative product, a commercially available anti-adhesion material was similarly evaluated. Got Rum.
【００２５】麻酔下で７週齢のＷｉｓｔａｒラット腹部
を剃毛し、腹部を消毒後、腹部の皮膚および筋組織を正
中線で切開した。腹壁内側の腸骨静脈を切断し、絹糸を
結んで止血した。血管切断部および絹糸を覆うように腹
壁に、酸化エチレンガスにて滅菌した１×１．５ｃｍの
フィルムを貼付して、腹部を縫合した。１週間後に開腹
して、癒着の有無を観察し、癒着防止効果を評価した。
結果は以下の通りである。Under anesthesia, the abdomen of a 7-week-old Wistar rat was shaved, the abdomen was disinfected, and the skin and muscle tissues of the abdomen were incised at the midline. The iliac vein inside the abdominal wall was cut and tied with silk thread to stop bleeding. A 1 × 1.5 cm film sterilized with ethylene oxide gas was attached to the abdominal wall so as to cover the blood vessel cut portion and the silk thread, and the abdomen was sutured. One week later, the abdomen was opened, and the presence or absence of adhesion was observed to evaluate the effect of preventing adhesion.
The results are as follows.
【００２６】
＜紫外線照射時間＞ ＜癒着発生率（％）＞
対照*1 ８９
０*2 ６２
１０ ４２
２０ ７７
４０ ９３
Interceed*3 ７０
Seprafilm*4 ８３
＊１：フィルムを貼付しない。
＊２：紫外線照射していないフィルムを貼付する。
＊３：Ｅｔｈｉｃｏｎ社製、登録商標。織布（ニット）
を貼付。
＊４：Ｇｅｎｚｙｍｅ社製、登録商標。フィルムを貼
付。<Ultraviolet irradiation time><Adhesion occurrence rate (%)> Control * 1 890 * 2 62 10 42 20 77 40 93 Interceed * 3 70 Seprafilm * 4 83 * 1: No film is attached. * 2: Attach a film that has not been irradiated with ultraviolet light. * 3: A registered trademark manufactured by Ethicon. Woven cloth (knit)
Attached. * 4: A registered trademark manufactured by Genzyme. Attach the film.
【００２７】上記の結果から明らかなように、紫外線を
１０時間照射したフィルムが最も高い癒着防止効果を示
した。紫外線を照射して架橋しないと分解が速すぎるた
め、癒着防止効果が低く、一方２０時間以上の紫外線照
射では、分解吸収が遅く、異物反応を誘発し逆に癒着を
引き起こしてしまう。As is clear from the above results, the film irradiated with ultraviolet rays for 10 hours showed the highest anti-adhesion effect. If it is not cross-linked by irradiating with ultraviolet rays, the decomposition will be too fast, and the effect of preventing adhesion will be low. On the other hand, if irradiated with ultraviolet rays for 20 hours or more, decomposition and absorption will be slow, and foreign matter reaction will be induced to cause adhesion.
【００２８】［実施例２］殺菌用の紫外線ランプ（東芝
（株）製、ＧＬ−１５）を使用して、実施例１で得られ
たゼラチンフィルムに１５ワットの紫外線を６０ｃｍの
距離で５、１０、２０、４０時間照射し（表と裏を半分
の時間ずつ）、以下の生体吸収分解性試験の評価に使用
した。結果は図１に示す通りである。[Example 2] Using a UV lamp for sterilization (GL-15, manufactured by Toshiba Corp.), the gelatin film obtained in Example 1 was exposed to 15 watts of ultraviolet light at a distance of 60 cm for 5 minutes. Irradiation was carried out for 10, 20, and 40 hours (half time for front and back), and used for evaluation of the following bioabsorption-degradability test. The results are shown in FIG.
【００２９】フィルム（１×１．５ｃｍ）を酸化エチレ
ンガス滅菌し、次のようにして埋入試験を行なった。フ
ィルムの乾燥重量を測定した後、７週齢のＷｉｓｔａｒ
ラットの腹腔内に埋入した。一定期間後にラットを犠牲
死させ、腹腔内からフィルムを摘出した。摘出したフィ
ルムを軽く洗浄し、真空乾燥器を用いて完全に乾燥させ
た後、重量を測定した。フィルムの初期重量と残存重量
との比からゼラチンフィルムの分解性を測定した。The film (1 × 1.5 cm) was sterilized with ethylene oxide gas, and an embedding test was conducted as follows. After measuring the dry weight of the film, Wistar at 7 weeks of age
The rat was implanted in the abdominal cavity. After a certain period of time, the rat was sacrificed and the film was removed from the abdominal cavity. The excised film was lightly washed, completely dried using a vacuum drier, and then weighed. The degradability of the gelatin film was measured from the ratio of the initial weight of the film and the residual weight.
【００３０】図１から明らかなように、紫外線を１０時
間照射して架橋させたゼラチンフィルムは２日間で分解
し生体に吸収されているため、実施例１にみられるよう
に、優れた癒着防止効果を示したものと考えられる。一
方、紫外線を２０時間以上照射して架橋させたゼラチン
フィルムは分解して吸収されるまでに２日以上を要した
ため、低い癒着防止効果を示したものと考えられる。As is apparent from FIG. 1, the gelatin film cross-linked by irradiating with ultraviolet rays for 10 hours is decomposed in 2 days and absorbed by the living body. Therefore, as shown in Example 1, excellent adhesion prevention was observed. It is considered to have shown the effect. On the other hand, the gelatin film cross-linked by irradiating ultraviolet rays for 20 hours or more took 2 days or more to be decomposed and absorbed, and therefore, it is considered that the gelatin film showed a low adhesion preventing effect.
【００３１】図１に示されるように、５〜１５時間紫外
線照射されたゼラチンフィルムは１〜７日間程度の生体
分解吸収時間を有するものと推測され、高い癒着防止効
果が期待できる。As shown in FIG. 1, the gelatin film irradiated with ultraviolet rays for 5 to 15 hours is estimated to have a biodegradation and absorption time of about 1 to 7 days, and a high anti-adhesion effect can be expected.
【００３２】［実施例３］殺菌用の紫外線ランプ（東芝
（株）製、ＧＬ−１５）を使用して、実施例１で得られ
たゼラチンフィルムに１５ワットの紫外線を６０ｃｍの
距離で１、５、１０、２０、４０時間照射し（表と裏を
半分の時間ずつ）、以下に示す方法で含水率を測定し、
結果を図２に示した。[Example 3] Using a UV lamp for sterilization (GL-15, manufactured by Toshiba Corp.), the gelatin film obtained in Example 1 was irradiated with 15 watts of ultraviolet ray at a distance of 60 cm for 1, Irradiate for 5, 10, 20, 40 hours (half time for front and back), and measure the water content by the following method.
The results are shown in Fig. 2.
【００３３】フィルムをリン酸緩衝水溶液（ＰＢＳ
（−））に２５℃で２時間浸漬した後、さらに蒸留水に
２５℃で６時間浸漬した。このフィルムの重量を測定
し、湿潤重量とした。その後、このフィルムを真空乾燥
器中で完全に乾燥させ、重量を測定し、乾燥重量とし、
以下の式に従い、含水率を算出した。
含水率（％）＝［（湿潤重量−乾燥重量）／湿潤重量］
×１００The film is treated with a phosphate buffered aqueous solution (PBS).
After dipping in (-)) at 25 ° C for 2 hours, it was further dipped in distilled water at 25 ° C for 6 hours. The weight of this film was measured and taken as the wet weight. Then, this film is completely dried in a vacuum dryer, and the weight is measured to obtain the dry weight,
The water content was calculated according to the following formula. Moisture content (%) = [(wet weight-dry weight) / wet weight]
× 100
【００３４】図２から明らかなように、紫外線を５〜１
５時間照射したゼラチンフィルムは８５〜９５％の範囲
の含水率を示しており、癒着防止膜として使用する場
合、生体組織に対する追従性（フィット）が優れてい
る。As is apparent from FIG.
The gelatin film irradiated for 5 hours shows a water content in the range of 85 to 95%, and when used as an adhesion-preventing film, it has excellent conformability (fit) to living tissue.
【００３５】［実施例４］殺菌用の紫外線ランプ（東芝
（株）製、ＧＬ−１５）を使用して、実施例１で得られ
たゼラチンフィルムに１５ワットの紫外線を６０ｃｍの
距離で５、１０、２０、４０時間照射し（表と裏を半分
の時間ずつ）、以下に示す方法でグルコース透過性を測
定し、結果を図３に示した。Example 4 Using a UV lamp for sterilization (GL-15, manufactured by Toshiba Corp.), the gelatin film obtained in Example 1 was exposed to 15 watts of ultraviolet light at a distance of 60 cm for 5 minutes. Irradiation was performed for 10, 20 and 40 hours (half time for front and back), and glucose permeability was measured by the following method, and the results are shown in FIG.
【００３６】フィルムをリン酸緩衝水溶液（ＰＢＳ
（−））に２０℃で２時間浸漬した後、２チャンバー拡
散セルを用いてグルコースの透過性を次のようにして評
価した。含水したフィルムをポリエステルメッシュで挟
み、ドナーチャンバーとレセプターチャンバーの間に挿
入した。ドナーチャンバーに１０ｍｇ／ｍｌに調製した
グルコースのＰＢＳ（−）溶液を５ｍｌ入れ、レセプタ
ーチャンバーにはＰＢＳ（−）溶液を５ｍｌ入れた。両
チャンバーを３７℃で一定速度で攪拌しつつ、経時的に
レセプターチャンバーより２０μｌずつ採取し、グルコ
ースＢ−テストワコー（和光純薬株式会社）を用いてグ
ルコース濃度を測定した。ゼラチンフィルムの拡散係数
は、以下のＦｉｃｋの法則に従う。
ｌｎ（１−２ＣB／Ｃ0）＝（−２ＡＤ／ＬＶ）×ｔThe film was treated with an aqueous phosphate buffer solution (PBS
After dipping in (-)) at 20 ° C. for 2 hours, glucose permeability was evaluated as follows using a two-chamber diffusion cell. The hydrated film was sandwiched by polyester mesh and inserted between the donor chamber and the receptor chamber. 5 ml of PBS (-) solution of glucose adjusted to 10 mg / ml was placed in the donor chamber, and 5 ml of PBS (-) solution was placed in the receptor chamber. While agitating both chambers at 37 ° C. at a constant rate, 20 μl of each sample was sampled from the receptor chamber over time, and the glucose concentration was measured using Glucose B-Test Wako (Wako Pure Chemical Industries, Ltd.). The diffusion coefficient of a gelatin film follows Fick's law below. ln (1-2C B / C 0) = (- 2AD / LV) × t
【００３７】ここで、ＣB は、ｔ秒後のレセプターチャ
ンバー中のグルコース濃度（ｍｇ／ｍｌ）を示す。Ｃ0
はドナーチャンバーの初期濃度（ｍｇ／ｍｌ）を示す。
Ａは拡散孔に面したゼラチンフィルムの面積（ｃｍ2）
、Ｄはグルコースの拡散係数（ｃｍ2／秒） 、Ｌはゼ
ラチンフィルムの厚さ（ｃｍ）、Ｖはチャンバー内水溶
液の体積（ｍｌ）を示す。Here, C B represents the glucose concentration (mg / ml) in the receptor chamber after t seconds. C 0
Indicates the initial concentration (mg / ml) in the donor chamber.
A is the area of the gelatin film facing the diffusion holes (cm 2 ).
, D is the diffusion coefficient of glucose (cm 2 / sec), L is the thickness of the gelatin film (cm), and V is the volume (ml) of the aqueous solution in the chamber.
【００３８】時間ｔに対し、ｌｎ（１−２ＣB／Ｃ0）を
プロットしたグラフから、傾きを読取り、拡散係数Ｄを
算出した。The slope was read from the graph in which ln (1-2C B / C 0 ) was plotted against the time t, and the diffusion coefficient D was calculated.
【００３９】図３から明らかなように、５〜１５時間紫
外線照射したゼラチンフィルムは好ましいグルコース透
過性を示している。As is clear from FIG. 3, the gelatin film irradiated with ultraviolet rays for 5 to 15 hours shows favorable glucose permeability.
【００４０】[0040]
【発明の効果】本発明の癒着防止材は、生体組織とよく
密着する他、高い含水率及びグルコース透過性を示し、
かつ生体吸収性で適度の吸収速度を有している。EFFECTS OF THE INVENTION The anti-adhesion material of the present invention has good water content and glucose permeability in addition to being well adhered to living tissues.
It is bioabsorbable and has an appropriate absorption rate.
【図１】実施例２において、紫外線照射時間を変化させ
た各種ゼラチンフィルムの生体吸収分解性試験の結果を
示すグラフである。FIG. 1 is a graph showing the results of a bioabsorption-degradability test of various gelatin films with different ultraviolet irradiation times in Example 2.
【図２】実施例３において、紫外線照射時間を変化させ
たゼラチンフィルムの含水率を示すグラフである。FIG. 2 is a graph showing the water content of a gelatin film obtained by changing the ultraviolet irradiation time in Example 3.
【図３】実施例４において、紫外線照射時間を変化させ
たゼラチンフィルムのグルコース透過性を示すグラフで
ある。FIG. 3 is a graph showing the glucose permeability of a gelatin film of Example 4 in which the ultraviolet irradiation time was changed.
───────────────────────────────────────────────────── フロントページの続き (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 (56)参考文献 特開 平６−306095（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) A61L 15/00 - 33/00 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hiroo Iwata 1-5-5 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka Prefecture 8-203 (72) Yoshito Rai, 2nd Gogasho-Okaya, Uji City, Kyoto Prefecture 182 (56) Reference Document JP-A-6-306095 (JP, A) (58) Fields investigated (Int.Cl. 7 , DB name) A61L 15/00-33/00
Claims (35)
の紫外線を、照射距離６０ｃｍで５〜１５時間照射して
架橋した架橋ゼラチンを含む癒着防止材。 1. Gelatin molded into a predetermined shape, 15 W
UV rays of 5 to 15 hours at an irradiation distance of 60 cm
An anti-adhesion material containing cross-linked gelatin.
項１記載の癒着防止材。 2. The gelatin contains glycerin.
Item 1. An adhesion preventing material according to item 1.
２記載の癒着防止材。 3. The method according to claim 1, wherein the form is sponge.
The anti-adhesion material described in 2.
項３記載の癒着防止材。 4. The sponge has a pore size of 5 μm or less.
Item 4. The adhesion preventing material according to item 3.
請求項３または 4 記載の癒着防止材。 5. The thickness is in the range of 50 to 500 μm.
The adhesion preventing material according to claim 3 or 4 .
２に記載の癒着防止材。 6. The film according to claim 1 or 2.
The anti-adhesion material described in 2.
る請求項６記載の癒着防止材。 7. The film has a thickness of 10 to 300 μm.
The adhesion prevention material according to claim 6.
記ゼラチンが紫外線照射により架橋しており、前記ゼラ
チンのグルコース拡散係数が、４×１０ −６ 〜１×１０
−５ ｃｍ ２ ／ｓである癒着防止材。 8. An adhesion preventive material containing gelatin, which comprises :
The gelatin is cross-linked by UV irradiation,
The glucose diffusion coefficient of Chin is 4 × 10 −6 to 1 × 10
An adhesion preventive material having a density of −5 cm 2 / s.
項８記載の癒着防止材。 9. The gelatin contains glycerin.
Item 8. An adhesion preventing material according to item 8.
は９に記載の癒着防止材。 10. The method according to claim 8, wherein the form is sponge.
Is the anti-adhesion material described in 9.
求項１０記載の癒着防止材。 11. A contract in which the sponge has a pore diameter of 5 μm or less.
The adhesion preventing material according to claim 10.
る請求項１０または１１記載の癒着防止材。 12. The thickness is in the range of 50 to 500 μm.
The anti-adhesion material according to claim 10 or 11.
は９に記載の癒着防止材。 13. The method according to claim 8, which is in the form of a film.
Is the anti-adhesion material described in 9.
ある請求項１３記載の癒着防止材。 14. A film having a thickness of 10 to 300 μm
The adhesion preventive material according to claim 13.
外線を、照射距離６０ｃｍで５〜１５時間照射するとい
う条件である請求項８から１４のいずれかに記載の癒着
防止材。 15. The irradiation condition of the ultraviolet ray is 15 W of purple.
Irradiate an outside line at an irradiation distance of 60 cm for 5 to 15 hours
The adhesion according to any one of claims 8 to 14, which is a condition to
Preventive material.
前記ゼラチンが紫外線照射により架橋しており、前記ゼ
ラチンの含水率が８５〜９５重量％の範囲である癒着防
止材。 16. An anti-adhesion material containing gelatin, comprising :
The gelatin is cross-linked by UV irradiation,
Adhesion prevention with a water content of ratin in the range of 85 to 95% by weight
Stop material.
求項１６記載の癒着防止材。 17. The contract in which the gelatin contains glycerin.
The adhesion prevention material according to claim 16.
たは１７に記載の癒着防止材。 18. The method according to claim 16, wherein the form is sponge.
Or the anti-adhesion material according to item 17.
求項１８記載の癒着防止材。 19. A contract in which the pore diameter of the sponge is 5 μm or less.
The adhesion prevention material according to claim 18.
る請求項１８または１９記載の癒着防止材。 20. The thickness is in the range of 50 to 500 μm.
The anti-adhesion material according to claim 18 or 19.
たは１７に記載の癒着防止材。 21. The method according to claim 16, wherein the form is a film.
Or the anti-adhesion material according to item 17.
ある請求項２１記載の癒着防止材。 22. A film having a thickness of 10 to 300 μm
The anti-adhesion material according to claim 21.
が、４×１０ −６ 〜１×１０ −５ ｃｍ ２ ／ｓである請求
項１６から２２のいずれかに記載の癒着防止材。 23. Glucose diffusion coefficient of the gelatin
Is 4 × 10 −6 to 1 × 10 −5 cm 2 / s.
Item 23. The adhesion preventive material according to any one of items 16 to 22.
外線を、照射距離６０ｃｍで５〜１５時間照射するとい
う条件である請求項１６から２３のいずれかに記載の癒
着防止材。 24. The irradiation condition of the ultraviolet ray is 15 W of purple
Irradiate an outside line at an irradiation distance of 60 cm for 5 to 15 hours
The healing according to any one of claims 16 to 23, which is a condition that
Anti-wear material.
０〜１７０℃の温度で熱処理をすることによりに架橋し
た架橋ゼラチンを含む癒着防止材。 25. Gelatin molded into a predetermined shape is
It is crosslinked by heat treatment at a temperature of 0 to 170 ° C.
Anti-adhesion material containing cross-linked gelatin.
求項２５記載の癒着防止材。 26. The contract in which the gelatin contains glycerin.
The adhesion preventing material according to claim 25.
たは２６記載の癒着防止材。 27. The method according to claim 25, wherein the form is sponge.
Or the anti-adhesion material described in 26.
求項２７記載の癒着防止材。 28. A contract in which the sponge has a pore diameter of 5 μm or less.
The adhesion prevention material according to claim 27.
る請求項２７または２８記載の癒着防止材。 29. The thickness is in the range of 50 to 500 μm.
The adhesion preventing material according to claim 27 or 28.
たは２６に記載の癒着防止材。 30. The method according to claim 25, wherein the form is a film.
Or the anti-adhesion material described in 26.
ある請求項３０記載の癒着防止材。 31. A film having a thickness of 10 to 300 μm
31. The adhesion preventing material according to claim 30.
９５重量％の範囲にある請求項２５から３１のいずれか
に記載の癒着防止材。 32. The water content of the crosslinked gelatin is from 85 to 85.
32. Any of claims 25 to 31 in the range of 95% by weight.
The anti-adhesion material described in.
数が、４×１０ −６ 〜１×１０ −５ ｃｍ ２ ／ｓである請
求項２５から３２のいずれかに記載の癒着防止材。 33. The glucose diffusion coefficient of the crosslinked gelatin
Contracts whose number is 4 × 10 −6 to 1 × 10 −5 cm 2 / s
The adhesion preventive material according to any one of claims 25 to 32.
方法であって、ゼラチンを所定形状に成形した後、１５
Ｗの紫外線を、照射距離６０ｃｍで５〜１５時間照射す
ることによりゼラチン内の分子を架橋させる製造方法。 34. Production of anti-adhesion material containing cross-linked gelatin
A method of forming gelatin into a predetermined shape,
Irradiate W ultraviolet light at an irradiation distance of 60 cm for 5 to 15 hours.
A method of manufacturing by which the molecules in gelatin are crosslinked.
方法であって、ゼラチンを所定形状に成形した後、１２
０〜１７０℃の温度で熱処理することによりゼラチン内
の分子を架橋させる製造方法。 35. Production of anti-adhesion material containing cross-linked gelatin
A method of forming gelatin into a predetermined shape,
Inside gelatin by heat treatment at a temperature of 0-170 ℃
Manufacturing method of cross-linking the molecules of.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20564698A JP3517358B2 (en) | 1998-07-21 | 1998-07-21 | Anti-adhesion material and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20564698A JP3517358B2 (en) | 1998-07-21 | 1998-07-21 | Anti-adhesion material and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000037450A JP2000037450A (en) | 2000-02-08 |
| JP3517358B2 true JP3517358B2 (en) | 2004-04-12 |
Family
ID=16510348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20564698A Expired - Fee Related JP3517358B2 (en) | 1998-07-21 | 1998-07-21 | Anti-adhesion material and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3517358B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8741969B2 (en) | 2005-08-05 | 2014-06-03 | Gunze Limited | Anti-adhesion membrane |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268400C (en) | 2001-06-15 | 2006-08-09 | 郡是株式会社 | Synechia inhibitory material |
| JP4295482B2 (en) * | 2002-08-08 | 2009-07-15 | グンゼ株式会社 | Anti-adhesive material |
| JP4554916B2 (en) * | 2002-12-16 | 2010-09-29 | グンゼ株式会社 | Medical film |
| CA2509622C (en) | 2002-12-16 | 2012-02-21 | Gunze Limited | Medical film comprising gelatin and reinforcing material |
| JP5413786B2 (en) * | 2009-09-09 | 2014-02-12 | 国立大学法人大阪大学 | Cross-linked structure of protein polymer |
| JP5578874B2 (en) * | 2010-02-10 | 2014-08-27 | グンゼ株式会社 | Bioabsorbable self-adhesive anti-adhesion material |
| EP2740499B1 (en) | 2011-08-02 | 2018-09-26 | Dainichiseika Color & Chemicals Mfg. Co., Ltd. | Anti-adhesion medical material and method for producing same |
| JP6944858B2 (en) * | 2016-12-05 | 2021-10-06 | グンゼ株式会社 | Nerve adhesion prevention wrapping material |
| JP7042730B2 (en) | 2018-10-31 | 2022-03-28 | 株式会社ハイレックスコーポレーション | In vivo non-degradable adhesion inhibitor |
| EP4032557A4 (en) * | 2019-09-18 | 2023-10-18 | National Institute for Materials Science | Biological tissue adhesive sheet , biological tissue reinforcing material kit, and method for producing biological tissue adhesive sheet |
| WO2021054232A1 (en) * | 2019-09-18 | 2021-03-25 | 国立研究開発法人物質・材料研究機構 | Biological tissue adhesive sheet, biological tissue reinforcing material kit, and method for manufacturing biological tissue adhesive sheet |
-
1998
- 1998-07-21 JP JP20564698A patent/JP3517358B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8741969B2 (en) | 2005-08-05 | 2014-06-03 | Gunze Limited | Anti-adhesion membrane |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2000037450A (en) | 2000-02-08 |
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