JP4912565B2 - Biodegradable absorbable adhesive medical material - Google Patents
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- JP4912565B2 JP4912565B2 JP2003415974A JP2003415974A JP4912565B2 JP 4912565 B2 JP4912565 B2 JP 4912565B2 JP 2003415974 A JP2003415974 A JP 2003415974A JP 2003415974 A JP2003415974 A JP 2003415974A JP 4912565 B2 JP4912565 B2 JP 4912565B2
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本発明は、生分解性高分子を溶解した水溶液を接着成分とし、生体由来の低分子を硬化成
分とする、生体用組織接着剤等の二成分系の生体内で分解吸収性がある粘着性医用材料に
関する。
The present invention is a water solution of a biodegradable polymer as the adhesive component, the low-molecular-derived biological and curing component, there is resorbable in vivo of the two-component system such as biomedical tissue adhesive The present invention relates to an adhesive medical material.
外科手術における皮膚、臓器、血管などの創部の閉鎖・接合等において、フィブリン系接
着剤、シアノアクリレート系接着剤、ポリウレタン系接着剤などが生体組織用接着剤とし
て臨床的に使用されている。以上に示した接着剤は毒性や接着強度の面において、そのい
ずれかに欠点をもっており、現在は生体高分子を用いた生体内分解吸収性を持つ生体組織
用接着剤が開発されつつある（例えば、特許文献１、２）。
Fibrin-based adhesives, cyanoacrylate-based adhesives, polyurethane-based adhesives and the like are clinically used as biological tissue adhesives in closing and joining wounds such as skin, organs and blood vessels in surgery. The adhesives shown above have disadvantages in either of the toxicity and adhesive strength, and currently, biological tissue adhesives using biopolymers and having biodegradability are being developed (for example, Patent Documents 1 and 2).
本発明者らは、生分解性高分子（コラーゲンやゼラチンなど）の有機溶媒溶液若しくは水
溶液又は水−有機溶媒混合溶液を接着成分とし、クエン酸回路に存在するジ又はトリカル
ボン酸のカルボキシル基を電子吸引性基によって少なくとも１つ以上修飾した低分子誘導
体を硬化成分とする二成分系の生体内分解吸収性粘着性医用材料を開発した（特願２００
３−３５７１０、非特許文献１〜６）。
The present inventors use an organic solvent solution or an aqueous solution of a biodegradable polymer (collagen, gelatin, etc.) or a water-organic solvent mixed solution as an adhesive component, and convert the carboxyl group of di- or tricarboxylic acid present in the citric acid circuit to an electron. A two-component biodegradable absorbable adhesive medical material having a low molecular derivative modified with at least one attractive group as a curing component has been developed (Japanese Patent Application No. 200).
3-35710, non-patent documents 1-6).
本発明者らが開発した上記の二成分系接着剤は、生体軟組織の強度に匹敵する高い接着強
度を有し、生体に対する毒性が低く生体親和性に優れた医療用の二成分系接着剤である。
しかし、接着成分濃度と硬化成分濃度が決まると、硬化時間をコントロールすることがで
きなかった。そこで、この二成分系の接着剤を用いる際に、生体組織の接着部位に応じて
硬化時間を制御できる生体組織用接着剤の開発が望まれている。
The above-mentioned two-component adhesive developed by the present inventors is a two-component adhesive for medical use having high adhesive strength comparable to that of living soft tissue, low toxicity to the living body and excellent biocompatibility. is there.
However, once the adhesive component concentration and the curing component concentration were determined, the curing time could not be controlled. Therefore, when using this two-component adhesive, it is desired to develop an adhesive for living tissue that can control the curing time according to the bonding site of the living tissue.
このような問題点を解決するため、本発明では、二成分系の接着剤の接着成分中に無機塩
を添加すること、又は接着成分をりん酸緩衝溶液に溶解することで硬化時間をコントロー
ルできる生体内分解吸収性粘着性医用材料を開発した。
In order to solve such problems, in the present invention, the curing time can be controlled by adding an inorganic salt to the adhesive component of a two-component adhesive or by dissolving the adhesive component in a phosphate buffer solution. Biodegradable absorbable adhesive medical material was developed.
すなわち、本発明は、生分解性高分子と無機塩を溶解した水溶液を接着成分とし、クエン
酸回路に存在するジ又はトリカルボン酸のカルボキシル基を、スクシンイミジル、スルホ
スクシンイミジル、マレイミジル、フタルイミジル、イミダゾールイル、ニトロフェニル
、トレジルの１種又は２種以上の組み合わせから選ばれる電子吸引性基によって、少なく
とも１つ以上修飾した生体由来の低分子を硬化成分とする二成分系の生体内分解吸収性粘
着性医用材料を提供する。
That is, the present invention is an aqueous solution prepared by dissolving a biodegradable polymer and an inorganic salt and an adhesive component, citric
The carboxyl group of the di- or tricarboxylic acid present in the acid circuit is succinimidyl, sulfo
Succinimidyl, maleimidyl, phthalimidyl, imidazolyl, nitrophenyl
Depending on the electron-withdrawing group selected from one or a combination of two or more of trezil,
Both provide one or more modified biodegradable and absorbable adhesive medical material of the two-component system to cure component low-molecular-derived biological.
また、本発明は、生分解性高分子を溶解したりん酸緩衝溶液を接着成分とし、クエン酸回
路に存在するジ又はトリカルボン酸のカルボキシル基を、スクシンイミジル、スルホスク
シンイミジル、マレイミジル、フタルイミジル、イミダゾールイル、ニトロフェニル、ト
レジルの１種又は２種以上の組み合わせから選ばれる電子吸引性基によって、少なくとも
１つ以上修飾した生体由来の低分子を硬化成分とすることを特徴とする二成分系の生体内
分解吸収性粘着性医用材料を提供する。
Further, the present invention is a biodegradable polymer phosphate buffer solution prepared by dissolving the adhesive component, citric Sankai
The carboxyl group of the di- or tricarboxylic acid present in the pathway is succinimidyl, sulfosuku
Cinimidyl, maleimidyl, phthalimidyl, imidazolyl, nitrophenyl,
Depending on the electron-withdrawing group selected from one or a combination of two or more of resiles, at least
Providing one or more modified biodegradable and absorbable adhesive medical material of the two-component system, characterized in that the curing component low-molecular-derived biological.
生分解性高分子と無機塩を溶解する水溶液は、蒸留水、緩衝液が挙げられる。 Aqueous solution for dissolving the biodegradable polymer and the inorganic salt, distilled water, and a buffer.
また、無機塩としては、塩化物塩、硫酸塩、硝酸塩、りん酸塩、炭酸塩、ほう酸塩の１種
又は２種以上の組み合わせが挙げられる。
Examples of the inorganic salts, chlorides, sulfates, nitrates, phosphates, carbonates, and Sega Awa set of one or more borate.
また、接着成分中の生分解性高分子は、コラーゲン、アテロコラーゲン、アルカリ処理コ
ラーゲン、ゼラチン、ケラチン、アルブミン、グロブリン、フィブリノーゲン、グリコサ
ミノグリカン、キチン、キトサンからなる群から選ばれる１種又は２種以上が挙げられる
。また、硬化成分の生体由来低分子は、クエン酸回路に存在するジ又はトリカルボン酸の
カルボキシル基を、電子吸引性基によって少なくとも１つ以上修飾したものが挙げられる
。
The biodegradable polymer in the adhesive component is one or two selected from the group consisting of collagen, atelocollagen, alkali-treated collagen, gelatin, keratin, albumin, globulin, fibrinogen, glycosaminoglycan, chitin, and chitosan. The above is mentioned . In addition, examples of the biologically derived small molecule of the curable component include those obtained by modifying at least one carboxyl group of di- or tricarboxylic acid existing in the citric acid circuit with an electron-withdrawing group.
本発明の医用材料は、生分解性高分子を溶解した水溶液中の無機塩の濃度又はりん酸緩衝
溶液のりん酸の濃度を変化させることで、硬化時間を制御することが可能である。また、
塩濃度又はりん酸の濃度を増加させることにより、硬化時間を短くすることができる。
Medical material of the present invention, by changing the concentration of the phosphoric acid concentrations or phosphate buffer solution of an inorganic salt in the aqueous solution obtained by dissolving the biodegradable polymer, it is possible to control the curing time. Also,
By increasing the concentration of the salt concentration or phosphoric acid, it is possible to shorten the curing time.
以上のような、本発明の二成分系の生体内分解吸収性粘着性医用材料は、生体用組織接着
剤として用いる場合、硬化時間を所望の時間に制御することが可能である。また、硬化時
間を短くすることができるため、短時間で組織を接着・封鎖することが可能になる。
When the two-component biodegradable and absorbable adhesive medical material of the present invention as described above is used as a biological tissue adhesive, the curing time can be controlled to a desired time. Further, since the curing time can be shortened, the tissue can be adhered and sealed in a short time.
生分解性高分子には、天然の生分解性高分子として、コラーゲン（数１０種類のタイプに
よらない）、アテロコラーゲン（数１０種類のタイプによらない）、アルカリ可溶化コラ
ーゲン（数１０種類のタイプによらない）、ゼラチン（数１０種類のタイプによらない）
、ケラチン、アルブミン、グロブリン、フィブリノーゲン、グリコサミノグリカン、キチ
ン、キトサン（脱アセチル化度、分子量によらない）からなる群から選ばれる１種又は２
種以上が挙げられる。
Biodegradable polymers include natural biodegradable polymers such as collagen (does not depend on tens of types), atelocollagen (does not depend on tens of types), alkali-solubilized collagen (several tens of types). Type), gelatin (does not depend on tens of types)
1 or 2 selected from the group consisting of keratin, albumin, globulin, fibrinogen, glycosaminoglycan, chitin, chitosan (degree of deacetylation, regardless of molecular weight)
More than species .
グリコサミノグリカンには、コンドロイチン硫酸、デルマタン硫酸、ヒアルロン酸、ペパ
ラン硫酸、ヘパリン、ケラタン硫酸、又はこれらの誘導体の１種又は２種の組み合わせが
含まれる。これらのグリコサミノグリカンは、分子量、由来する生物によらない。
無機塩には、例えば、塩化ナトリウム、硫酸ナトリウム、硝酸ナトリウム、リン酸水素二
ナトリウム、リン酸二水素ナトリウム、りん酸一ナトリウム、りん酸二ナトリウム、りん
酸三ナトリウム、炭酸ナトリウム、炭酸水素ナトリウム、又はこれらの１種又は２種以上
の組み合わせを用いることができる。無機塩中の陽イオンはナトリウムの他、カリウム等
の一価の陽イオン、もしくはカルシウム等の二価の陽イオン又はアルミニウム等の三価の
陽イオンを用いることができる。無機塩中の陰イオンは、塩化物イオン、硫酸イオン、硝
酸イオン、りん酸イオン、炭酸イオン、ほう酸塩イオンの１種又は２種以上の組み合わせ
であることが挙げられる。陰イオンは、１価よりも２価以上のものがより硬化時間短縮に
効果的であるため、生体に対する親和性を考慮しつつ、１価と２価の陰イオンを持つ無機
塩を組み合わせることが好ましい。
Glycosaminoglycans include one or two combinations of chondroitin sulfate, dermatan sulfate, hyaluronic acid, pepalan sulfate, heparin, keratan sulfate, or derivatives thereof. These glycosaminoglycans are independent of the molecular weight and the organism from which they are derived.
Inorganic salts include, for example, sodium chloride, sodium sulfate, sodium nitrate, disodium hydrogen phosphate, sodium dihydrogen phosphate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium carbonate, sodium bicarbonate, Alternatively, one or a combination of two or more of these can be used. As the cation in the inorganic salt, a monovalent cation such as potassium, a divalent cation such as calcium, or a trivalent cation such as aluminum can be used in addition to sodium. Examples of the anion in the inorganic salt include chloride ions, sulfate ions, nitrate ions, phosphate ions, carbonate ions, and borate ions. Since anions having a valence of 2 or more than monovalent are more effective for shortening the curing time, it is possible to combine inorganic salts having monovalent and divalent anions while taking into consideration the affinity for the living body. preferable.
硬化成分の生体由来低分子は、生体内のクエン酸回路に存在するジ又はトリカルボン酸の
カルボキシル基を電子吸引性基によって少なくとも１つ以上修飾したものが挙げられる。
クエン酸回路に存在するジ又はトリカルボン酸は、例えば、リンゴ酸、オキサル酢酸、ク
エン酸、cis−アコニット酸、２−ケトグルタル酸、又はこれらの誘導体である。
Biological low-molecular curing component include those carboxyl groups of di- or tricarboxylic acids present in the citric acid cycle in vivo and at least one or more modified by electron attractive groups.
The di- or tricarboxylic acid present in the citric acid cycle is, for example, malic acid, oxalic acetic acid, citric acid, cis-aconitic acid, 2-ketoglutaric acid, or derivatives thereof.
クエン酸回路に存在するジ又はトリカルボン酸を修飾する電子吸引性基としては、スクシ
ンイミジル、スルホスクシンイミジル、マレイミジル、フタルイミジル、イミダゾールイ
ル、ニトロフェニル、トレジルの１種又は２種以上の組み合わせである。添加する無機塩
の濃度は０．０１Ｍから１０．０Ｍであり、水溶液中に無機塩が溶けうる濃度範囲でよい
。より好ましくは、０．１Ｍから１．０Ｍである。
Examples of the electron withdrawing group for modifying a di- or tricarboxylic acid is present in the citric acid cycle, succinimidyl, sulfosuccinimidyl, maleimidyl, phthalimidyl, imidazolyl, nitrophenyl, in one or more combinations of Toreji Le is there. The concentration of added inorganic salt is 10.0M from 0.01 M, inorganic salt may range in concentration can dissolve in an aqueous solution. More preferably, it is 0.1M to 1.0M.
生分解性高分子と生体由来低分子の割合は、無機塩を添加した蒸留水、緩衝液等の水溶液
中の生分解性高分子０．０１〜８０重量％に対し、生体由来低分子が水溶液に溶けうる濃
度範囲でよく、すなわち、０．０１〜１０００ｍＭとする。水溶液中の生分解性高分子の
より好ましい範囲は、生分解性高分子が水溶液に溶けうる濃度範囲でよく、すなわち、１
０〜６０重量％である。好ましくは、０〜１００℃、より好ましくは、生分解性高分子の
変性が起こらないなるべく低い温度範囲、すなわち、４〜６０℃で反応させる。なお、生
分解性高分子と生体由来低分子の配合に際しては、均一に反応させるため、双方を適宜濃
度の溶液として混合するのが好ましい。
The proportion of the biodegradable polymer and biological low-molecular, the distilled water with the addition of inorganic salts, to the biodegradable polymer 0.01 to 80 wt% in aqueous solution such as a buffer solution, biogenic low-molecular May be in a concentration range that can be dissolved in an aqueous solution , that is, 0.01 to 1000 mM. A more preferred range of the biodegradable polymer in the aqueous solution may be in the range of concentrations biodegradable polymer may dissolve in the aqueous solution, i.e., 1
0 to 60% by weight. The reaction is preferably performed at 0 to 100 ° C., more preferably at a temperature range as low as possible without denaturation of the biodegradable polymer, that is, 4 to 60 ° C. Note that when compounding the biodegradable polymer and biological low-molecular, in order to uniformly react, preferably mixed as a solution of appropriate concentration both.
また、接着成分及び硬化成分を作成するための溶媒としては、生理食塩水、炭酸水素ナト
リウム緩衝液、ホウ酸緩衝液、リン酸緩衝液に無機塩を添加した溶媒が挙げられる。これ
らの溶媒を使用することにより、接着剤を付着させた周囲の生体組織を浸透圧、ｐＨの変
化により壊死させないようにすることができる。
Examples of the solvent for preparing the adhesive component and the curing component include a solvent obtained by adding an inorganic salt to physiological saline, sodium bicarbonate buffer, borate buffer, and phosphate buffer. By using these solvents, it is possible to prevent the surrounding living tissue to which the adhesive is attached from being necrotic due to changes in osmotic pressure and pH.
生分解性高分子を溶解した水溶液を接着成分とする場合は、無機塩の濃度を変化させるこWhen using an aqueous solution in which a biodegradable polymer is dissolved as an adhesive component, the concentration of the inorganic salt can be changed.
とによって硬化成分による硬化時間を制御できる。And the curing time by the curing component can be controlled.
生分解性高分子を溶解したりん酸緩衝溶液を接着成分とする場合はりん酸の濃度を変化さ
せることによって硬化成分による硬化時間を制御できる。りん酸緩衝溶液のｐＨは、５〜
８までの範囲の増減が可能である。りん酸二水素ナトリウムとりん酸水素二ナトリウムの
濃度を、０．０１Ｍから０．３Ｍまで制御することによってｐＨ変化が可能である。
Of changing the concentration when the biodegradable polymer phosphate buffer solution prepared by dissolving the adhesive component is phosphoric acid
It was able to control the curing time by curing components by Rukoto. The pH of the phosphate buffer solution is 5 to
The range up to 8 can be increased or decreased. The sodium dihydrogen phosphate and the concentration of phosphate disodium hydrogen, it is possible to p H change by controlling the 0.01M to 0.3 M.
以上のような二成分系の生体内分解吸収性粘着性医用材料は、生体用組織接着剤として、
皮膚と皮膚などの軟組織間の接着、骨と骨などの硬組織間の接着、骨と軟骨などの硬組織
と軟組織の接着を目的として用いられる。また、止血剤、血管塞栓材、シーラント、又は
動脈瘤の封止剤としても用いられる。なお、本発明の医療用接着材料は当該用途に適用後
は、一定期間経過すると吸収、消失する特性があり、体内に異物として残存することがな
い。
The two-component biodegradable absorbable adhesive medical material as described above is used as a tissue adhesive for living organisms.
It is used for adhesion between soft tissues such as skin and skin, adhesion between hard tissues such as bone and bone, and adhesion between hard tissues and soft tissue such as bone and cartilage. It is also used as a hemostatic agent, vascular embolic material, sealant, or aneurysm sealant. The medical adhesive material of the present invention has a characteristic of absorbing and disappearing after a certain period of time after being applied to the application, and does not remain as a foreign substance in the body.
二成分系の生体内分解吸収性粘着性医用材料の硬化時間について以下の実験により確認し
た。接着剤の硬化時間の計測は、以下の手順で行った。濃度を調整済みの無機塩添加水溶
液に接着成分である生分解性高分子としてゼラチン（豚由来の酸処理ゼラチン、SIGMA,G2
500、分子量5〜10万、等電点7〜9）を２５重量％となるように溶解する。このゼラチン溶
液を５０℃の湯浴中にて加熱しておく。室温にて同組成の無機塩添加水溶液に硬化成分で
あるクエン酸のカルボキシル基をＮ−ヒドロキシスクシンイミドで修飾した誘導体（ＣＡ
Ｄ）を接着成分に対して１００mＭとなるように溶解する。ゼラチン溶液４量に対して、
クエン酸誘導体（ＣＡＤ）溶液１量を加え、均一に混合する。従って、この混合溶液の最
終ゼラチン濃度は２０重量％である。
The curing time of the two-component biodegradable absorbable adhesive medical material was confirmed by the following experiment. The adhesive curing time was measured according to the following procedure. Concentrated inorganic salt added water
Acid-treated gelatin derived from gelatin (porcine a biodegradable polymer that is adhesive component to the liquid, SIGMA, G2
500, molecular weight 50,000 to 100,000,
D) is dissolved to 100 mM with respect to the adhesive component. For 4 gelatin solutions
Add 1 volume of citric acid derivative (CAD) solution and mix uniformly. Therefore, the final gelatin concentration of this mixed solution is 20% by weight.
この混合溶液を動的粘弾性装置（Haake社RheoStress１）に導入し、硬化時間（ゲル化時
間）を計測した。計測時の温度は生体内を模擬して３７℃とした。硬化時間は動的粘弾性
測定により得られる貯蔵弾性率（以下、G'）と損失弾性率（以下、G"）の値が一致する点
である。硬化前はG'＜G"であるのに対して硬化後はG'＞G"となる。
This mixed solution was introduced into a dynamic viscoelastic device (Hahe RheoStress 1), and the curing time (gelation time) was measured. The temperature at the time of measurement was set to 37 ° C. by simulating in vivo. Curing time is the point where the storage elastic modulus (hereinafter referred to as G ') obtained by dynamic viscoelasticity measurement and the loss elastic modulus (hereinafter referred to as G ") coincide. G'<G" before curing On the other hand, after curing, G ′> G ″.
上記の混合溶液において、水溶液に無機塩として硫酸ナトリウ(Na2SO4)を無添加、０．１
モル、０．２モル、０．３モル添加した場合の硬化時間を測定した。また、無機塩添加水
溶液に代えて、りん酸緩衝溶液（ｐＨ７）を用い、りん酸の濃度を無添加、０．１モル、
０．２モル、０．３モル添加した場合の硬化時間も同様に測定した。
In the above mixed solution, sodium sulfate (Na 2 SO 4 ) is not added as an inorganic salt to the aqueous solution,
The curing time when mol, 0.2 mol, and 0.3 mol were added was measured. Also, inorganic salt added water
Instead of the solution , a phosphate buffer solution (pH 7) was used, the concentration of phosphoric acid was not added, 0.1 mol,
The curing time when 0.2 mol and 0.3 mol were added was also measured in the same manner.
図１は、測定結果を示すグラフである。硫酸ナトリウムを添加することによりその濃度の
増加に応じて硬化時間は短縮される。また、同様に、りん酸緩衝溶液のりん酸の濃度の増
加に応じて硬化時間は短縮される。いずれの場合も、濃度０．２〜０．３モルで硬化時間
の大幅な短縮が可能であることが分かる。
FIG. 1 is a graph showing the measurement results. By adding sodium sulfate, the curing time is shortened as the concentration increases. Similarly, the curing time is shortened as the concentration of phosphate in the phosphate buffer solution increases. In any case, it can be seen that the curing time can be significantly shortened at a concentration of 0.2 to 0.3 mol.
本発明は、硬化時間をコントロールできる生体内分解吸収性粘着性医用材料を提供するも
ので、用途としては、生体用組織接着剤の他に止血材、血管栓塞材、シーラント、動脈瘤
の封止剤等、医療現場で二成分の接着材料を混合及び硬化させて用いる医用材料に用いる
ことができる。
The present invention provides a biodegradable and absorbable adhesive medical material capable of controlling the curing time. In addition to a biomedical tissue adhesive, the present invention includes a hemostatic material, a vascular plugging material, a sealant, and an aneurysm sealing. It can be used as a medical material used by mixing and curing a two-component adhesive material such as an agent in a medical field.
Claims (7)
ブミン、グロブリン、フィブリノーゲン、グリコサミノグリカン、キチン、キトサン、か
らなる群から選ばれる１種又は２種以上の生分解性高分子を溶解した水溶液を接着成分と
する二成分系の粘着性材料において、
クエン酸回路に存在するジ又はトリカルボン酸のカルボキシル基を、スクシンイミジル、
スルホスクシンイミジル、マレイミジル、フタルイミジル、イミダゾールイル、ニトロフ
ェニル、トレジルの１種又は２種以上の組み合わせから選ばれる電子吸引性基によって、
少なくとも１つ以上修飾した生体由来の低分子を硬化成分とし、
かつ前記水溶液に０．０１Ｍから１０．０Ｍの濃度の無機塩が溶解されていることを特徴
とする二成分系の生体内分解吸収性粘着性医用材料。 Collagen, atelocollagen, alkali solubilized collagen, gelatin, keratin, al
Bumine, globulin, fibrinogen, glycosaminoglycan, chitin, chitosan, or
In a two-component adhesive material having an adhesive component as an aqueous solution in which one or more biodegradable polymers selected from the group consisting of:
The carboxyl group of the di- or tricarboxylic acid present in the citric acid cycle is succinimidyl,
By an electron-withdrawing group selected from one or a combination of two or more of sulfosuccinimidyl, maleimidyl, phthalimidyl, imidazolyl, nitrophenyl, and trezyl,
At least one or more modified biologically derived small molecules are used as curing components,
A two-component biodegradable absorbable adhesive medical material, wherein an inorganic salt having a concentration of 0.01M to 10.0M is dissolved in the aqueous solution.
ブミン、グロブリン、フィブリノーゲン、グリコサミノグリカン、キチン、キトサン、か
らなる群から選ばれる１種又は２種以上の生分解性高分子を溶解したりん酸緩衝溶液を接
着成分とする二成分系の粘着性材料において、
クエン酸回路に存在するジ又はトリカルボン酸のカルボキシル基を、スクシンイミジル、
スルホスクシンイミジル、マレイミジル、フタルイミジル、イミダゾールイル、ニトロフ
ェニル、トレジルの１種又は２種以上の組み合わせから選ばれる電子吸引性基によって、
少なくとも１つ以上修飾した生体由来の低分子を硬化成分とし、
かつ前記りん酸緩衝溶液のりん酸二水素ナトリウム又はりん酸水素二ナトリウムの濃度が
０．０１Ｍ〜０．３Ｍ、ｐＨが５〜８に調整されていることを特徴とする二成分系の生体
内分解吸収性粘着性医用材料。 Collagen, atelocollagen, alkali solubilized collagen, gelatin, keratin, al
Bumine, globulin, fibrinogen, glycosaminoglycan, chitin, chitosan, or
In a two-component adhesive material using a phosphate buffer solution in which one or more biodegradable polymers selected from the group consisting of the above are dissolved as an adhesive component,
The carboxyl group of the di- or tricarboxylic acid present in the citric acid cycle is succinimidyl,
By an electron-withdrawing group selected from one or a combination of two or more of sulfosuccinimidyl, maleimidyl, phthalimidyl, imidazolyl, nitrophenyl, and trezyl,
At least one or more modified biologically derived small molecules are used as curing components,
In addition, the concentration of sodium dihydrogen phosphate or disodium hydrogen phosphate in the phosphate buffer solution is adjusted to 0.01 M to 0.3 M and the pH is adjusted to 5 to 8. Biodegradable absorbable adhesive medical material.
又は２種以上の組み合わせであることを特徴とする二成分系の生体内分解吸収性粘着性医
用材料。 The inorganic salt according to claim 1 is one or a combination of two or more of hydrochloride, sulfate, nitrate, phosphate, carbonate and borate, and is a two-component biodegradation Absorbable adhesive medical material.
特徴とする軟組織と軟組織、軟組織と硬組織、又は硬組織と硬組織を接着する生体用組織
接着剤。 A soft tissue and soft tissue, a soft tissue and a hard tissue, or a soft tissue and a hard tissue, or a biomedical tissue that adheres a hard tissue and a hard tissue, comprising the biodegradable and absorbable adhesive medical material according to claim 1 or 2 adhesive.
特徴とする止血材、血管栓塞材、シーラント又は動脈瘤の封止剤。 A hemostatic material, a vascular embolization material, a sealant, or an aneurysm sealant comprising the two-component biodegradable and absorbable adhesive medical material according to claim 1 or 2.
する請求項１記載の二成分系の生体内分解吸収性粘着性医用材料の使用方法。 The method for using a two-component biodegradable absorbable adhesive medical material according to claim 1, wherein the curing time by the curing component is controlled by changing the concentration of the inorganic salt.
することを特徴とする請求項２記載の二成分系の生体内分解吸収性粘着性医用材料の使用
方法。 3. The method for using a biodegradable bioabsorbable bioadhesive medical material according to claim 2, wherein the curing time by the curing component is controlled by changing the concentration of phosphoric acid in the phosphate buffer solution.
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