JPH07213597A - Twisted yarn of purified collagen-like substance, formed body of twisted yarn and their manufacture - Google Patents

Twisted yarn of purified collagen-like substance, formed body of twisted yarn and their manufacture

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Publication number
JPH07213597A
JPH07213597A JP6011715A JP1171594A JPH07213597A JP H07213597 A JPH07213597 A JP H07213597A JP 6011715 A JP6011715 A JP 6011715A JP 1171594 A JP1171594 A JP 1171594A JP H07213597 A JPH07213597 A JP H07213597A
Authority
JP
Japan
Prior art keywords
twisted yarn
substance
human
collagen
purified collagen
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.)
Pending
Application number
JP6011715A
Other languages
Japanese (ja)
Inventor
Tokuzo Nakagawa
徳三 中川
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BIO ENG LAB KK
Original Assignee
BIO ENG LAB KK
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by BIO ENG LAB KK filed Critical BIO ENG LAB KK
Priority to JP6011715A priority Critical patent/JPH07213597A/en
Publication of JPH07213597A publication Critical patent/JPH07213597A/en
Pending legal-status Critical Current

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Abstract

PURPOSE:To provide twisted yarn of purified collagen-like substance which has superior biocompatibility and mechanical strength, is substitutable with tissue and an internal organ at an affected part of a human body as time passes after application, and can control in vivo decomposability. CONSTITUTION:A thin and long piece of purified collagen-like substance in wet state obtained from human amnions or human villi is dried and twisted, and cross-linked and/or succinylated if necessary, then is formed into a sheet or a tube to be a formed body. Or a film of purified collagen-like substance obtained from human amnions or human villi is laminated on the formed body such as sheet and tube formed from the twisted yarn.

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【産業上の利用分野】本発明は、精製コラーゲン様物質
の撚り糸、この撚り糸から製造された成形体、及びこれ
らの製造方法に関し、更に詳しくは生体適合性、機械的
強度に優れ、適用後、経時的にヒト生体患部の組織や臓
器と置換して、疾患部や損傷部が自己の組織や臓器で修
復することを促進・補助し、自己修復が完了後は生体内
から分解、代謝、排泄され、かつ生体内分解性を所望の
条件に制御することができ、縫合糸、創傷保護材、創傷
補填材、創傷補綴材、癒着防止材などの生体用人工材料
又は人工血管、人工気管、人工食道、人工尿道、人工尿
管、人工皮膚などの人工臓器として利用される精製コラ
ーゲン様物質の撚り糸、この撚り糸から製造された成形
体、及びこれらの製造方法に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a twisted yarn of a purified collagen-like substance, a molded article produced from this twisted yarn, and a method for producing the same. More specifically, it is excellent in biocompatibility and mechanical strength, and after application, It replaces the tissues and organs of the affected part of the human body over time, and promotes and assists the repair of diseased parts and damaged parts with its own tissues and organs.After self-repair is completed, decomposition, metabolism, and excretion from the body And biodegradability can be controlled to desired conditions, and artificial biomaterials such as sutures, wound protectors, wound prostheses, wound prostheses, and adhesion prevention materials, artificial blood vessels, artificial trachea, artificial TECHNICAL FIELD The present invention relates to a twisted yarn of a purified collagen-like substance used as an artificial organ such as an esophagus, an artificial urethra, an artificial ureter, an artificial skin, a molded product produced from the twisted yarn, and a method for producing these.

【0002】[0002]

【従来の技術】生体臓器や生体組織の傷害や疾病を治療
するにあたって、傷害部位の治癒のために用いる創傷保
護材、外科手術により欠損する疾病部位の生体組織や生
体臓器の補綴材や補填材、外科手術による切開部位を縫
合する縫合糸などの生体用人工材料又は人工血管、人工
気管、人工食道、人工尿道、人工尿管、人工皮膚などの
人工臓器が用いられており、合成高分子材料や生体由来
材料から製造されている。
2. Description of the Related Art A wound protective material used for healing an injured portion of a living organ or a living tissue, a prosthesis material or a filling material for a living tissue or a living organ at a diseased portion which is lost by surgery. , Synthetic artificial materials such as bioartificial materials such as sutures for suturing surgical incisions or artificial blood vessels, artificial trachea, artificial esophagus, artificial urethra, artificial ureters, artificial skin, etc. are used. Manufactured from bio-derived materials.

【0003】これらの生体用人工材料や人工臓器は、生
体適合性のあること、安全性や有効性があることが要求
されており、適用後、所望の期間内に、患部の生体組織
や生体臓器を再生、修復しつつ、生体内で分解、代謝、
排泄され、最終的に患部の生体組織や生体臓器と置換し
て自己修復する機能を有するものが好ましく、この点で
は、合成高分子材料は、生体患部の組織や臓器と同化、
生着しない、適用部位がケロイド化又は異形化する、或
は生体内に永久に残存することに起因する不都合な諸症
状があるなどの生体適合性に欠ける問題がある。
[0003] These bioartificial materials and artificial organs are required to be biocompatible, safe and effective, and within a desired period after application, the living tissue or living body of the affected area is required. While regenerating and repairing organs, in vivo decomposition, metabolism,
It is preferably excreted and finally has a function of self-repairing by substituting the living tissue or organ of the affected area, and in this respect, the synthetic polymer material is assimilated with the tissue or organ of the affected area,
There is a problem of lack of biocompatibility, such as non-engraftment, keloidization or deformity of the application site, or various inconvenient symptoms caused by the fact that it permanently remains in the living body.

【0004】他方、生体由来材料として、ブタ、ウシ、
ウマなどの異種動物由来の組織や臓器を原料として用い
た、豚皮由来創傷保護材、ウマ心のう膜由来創傷補綴
材、羊腸由来縫合糸などの生体用人工材料やブタ心臓大
動脈弁由来の生体弁、ウシ頸動脈由来の人工血管などの
人工臓器が研究開発され、その多くが医療用に用いられ
ている。しかしながら、異種動物由来の組織や臓器を用
いているため異種生体反応が起きるなどの生体適合性に
欠けるので、グルタールアルデヒド架橋、サクシニル化
処理などの化学的修飾や熱架橋、或は紫外線照射、電子
線照射、放射線照射による架橋処理などの物理的修飾が
必要となり、これらの化学的修飾や物理的修飾により生
体内分解性と置換性を欠いてしまう。すなわち、治療後
も異物として患者の生体内に異物として残存するため、
合成高分子材料の場合と同様な問題が起きるので、場合
によっては再手術により新しい生体用人工材料又は人工
臓器と取り換える必要がある。
On the other hand, as biological materials, pig, cow,
Using tissue and organs derived from xenogeneic animals such as horses as raw materials, artificial wound materials derived from pig skin, wound prostheses derived from equine pericardium, sutures derived from sheep's intestine, and artificial materials derived from porcine heart aortic valve. Artificial organs such as biological valves and artificial blood vessels derived from bovine carotid arteries have been researched and developed, and most of them are used for medical purposes. However, since it uses a tissue or organ derived from a different animal and lacks biocompatibility such as a different biological reaction, glutaraldehyde cross-linking, chemical modification such as succinylation treatment, heat cross-linking, or UV irradiation, Physical modification such as cross-linking treatment by electron beam irradiation or radiation irradiation is required, and biodegradability and substitutability are lost due to these chemical modification and physical modification. That is, since it remains as a foreign body in the patient's living body even after treatment,
Since the same problem as in the case of the synthetic polymer material occurs, it may be necessary to replace it with a new bioartificial material or artificial organ by reoperation in some cases.

【0005】また生体由来材料として、ヒト脳硬膜やヒ
ト大腿筋膜を原料として用いた同種置換用創傷補填材が
使用されている。しかしながら、これらの生体用人工材
料はシート状にしか形成できず、その他の形状には成形
できない。さらにヒト脳硬膜やヒト大腿筋膜は、ヒト屍
体のみから採取するため、極めて供給量が乏しく、極め
て高価である、さらには社会通念など医道上に問題があ
る。
Further, as a biologically derived material, a wound replacement material of the same type using human dura mater or human fascia lata as a raw material is used. However, these bioartificial materials can be formed only in a sheet shape, and cannot be formed in other shapes. Further, since human dura mater and human fascia lata are collected only from human corpses, the supply amount is extremely low and extremely expensive, and there is a medical practice problem such as social belief.

【0006】[0006]

【発明が解決しようとする課題】本発明者は、上記した
問題点を解決すべく鋭意検討した結果、医療廃棄物とし
て処分されるヒト胎児膜を構成するヒト羊膜又はヒト絨
毛膜から得られた湿潤状態の精製コラーゲン様物質を乾
燥しながら撚ると、再度湿潤状態にしても撚りが戻ら
ず、かつ優れた機械的強度を保持し、さらに撚り糸はシ
ート状又はチューブ状などに成形することができ、得ら
れた成形体も優れた機械的強度を有することを見出し、
本発明を完成するに至った。すなわち、本発明は、生体
適合性、機械的強度に優れ、適用後は経時的にヒト生体
患部の組織や臓器と置換して疾患部や損傷部が自己の組
織や臓器で修復することを促進、補助し、自己修復が完
了後は生体内から分解、代謝、排泄され、かつ生体内分
解性を制御できる精製コラーゲン様物質の撚り糸、この
撚り糸から製造された成形体及びこれらの製造方法を提
供することを目的とする。
DISCLOSURE OF THE INVENTION The inventors of the present invention have conducted extensive studies to solve the above-mentioned problems, and as a result, obtained from human amniotic membrane or human chorion constituting human fetal membrane to be disposed of as medical waste. When the purified collagen-like substance in a wet state is twisted while being dried, the twist does not return even if it is wet again, and excellent mechanical strength is maintained. Furthermore, the twisted yarn can be formed into a sheet or a tube. Found that the obtained molded body also has excellent mechanical strength,
The present invention has been completed. That is, the present invention is excellent in biocompatibility and mechanical strength, and after application, it is replaced with a tissue or an organ of a human living body affected area over time to promote repair of a diseased portion or a damaged portion with its own tissue or organ. Provided are a twisted yarn of a purified collagen-like substance which can be decomposed, metabolized and excreted from the living body after completion of self-repair, and whose biodegradability can be controlled, a molded article produced from this twisted yarn, and a method for producing these. The purpose is to do.

【0007】[0007]

【課題を解決するための手段】すなわち、本発明は、ヒ
ト羊膜又はヒト絨毛膜から得られた精製コラーゲン様物
質の細長片に撚りをかけた撚り糸;湿潤状態の該精製コ
ラーゲン様物質の細長片を乾燥しながら撚り、必要に応
じて架橋処理及び/またはサクシニル化処理を施す撚り
糸の製造方法;該撚り糸をシート状又はチューブ状に成
形した成形体;該撚り糸を湿潤状態にした後、シート状
又はチューブ状に成形し、次いで必要に応じて架橋処理
及び/またはサクシニル化処理を施した後、乾燥する成
形体の製造方法;該成形体の表面に、ヒト羊膜又はヒト
絨毛膜から得られた精製コラーゲン様物質の膜を積層し
た成形体;並びに該成形体の表面に、ヒト羊膜又はヒト
絨毛膜から得られた精製コラーゲン様物質の膜を積層し
た後、必要に応じて架橋処理及び/またはサクシニル化
処理を施した後、乾燥する成形体の製造方法である。
Means for Solving the Problems That is, the present invention provides a twisted yarn obtained by twisting a strip of a purified collagen-like substance obtained from human amnion or human chorion; a strip of the purified collagen-like substance in a wet state. A twisted yarn which is twisted while being dried, and optionally subjected to a cross-linking treatment and / or a succinylation treatment; a molded article obtained by molding the twisted yarn into a sheet or a tube; Alternatively, a method for producing a molded product, which is formed into a tubular shape, and then optionally subjected to a crosslinking treatment and / or a succinylation treatment, and then dried; on the surface of the molded product, obtained from human amniotic membrane or human chorion membrane A molded article in which a membrane of a purified collagen-like substance is laminated; and a membrane of a purified collagen-like substance obtained from human amniotic membrane or human chorion is laminated on the surface of the molded article, and if necessary. It was subjected to a crosslinking treatment and / or succinylated process, a process for producing a molded article to be dried.

【0008】本発明で用いる精製コラーゲン様物質は、
後述する処理によりヒト羊膜又はヒト絨毛膜から上皮
層、基底膜層及び繊維芽細胞層を除去した緻密層のみか
らなる。緻密層は、ヒトのI型、III型、V型及びX
VI型コラーゲンを主成分としているため、生体皮膜や
繊維芽細胞を増殖するための基質材料として好適な性質
及び生体適合性に優れ、かつ好適な機械的強度を有して
いる。
The purified collagen-like substance used in the present invention is
It consists only of a compact layer obtained by removing the epithelial layer, basement membrane layer and fibroblast layer from human amniotic membrane or human chorion by the treatment described below. Dense layers are human type I, type III, type V and X
Since it contains VI type collagen as a main component, it has excellent properties and biocompatibility suitable as a substrate material for proliferating biological membranes and fibroblasts, and also has suitable mechanical strength.

【0009】精製コラーゲン様物質は、以下のようにし
て製造される。先ず、無感染症産婦の分娩直後の一体と
なったヒト胎児膜、胎盤及び臍帯から胎児膜のみを分離
し、塩化ベンザルコニウム溶液又は臭化ベンザルコニウ
ム溶液中で、羊膜、絨毛膜、被包脱落膜及び床脱落膜の
4層からなる胎児膜から羊膜及び絨毛膜を剥離し、次い
でフィシンを用いた酵素処理を施し、さらに超音波洗浄
処理を施して残存する上皮層、基底膜層及び繊維芽細胞
層を除去してヒトのI型、III型、V型及びXVI型
コラーゲンを主成分とする緻密層のみからなる無菌、無
ウィルス、無異物、及び無発熱性物質の精製コラーゲン
様物質の膜を得る。
The purified collagen-like substance is manufactured as follows. First, only the fetal membrane is separated from the integrated human fetal membrane, placenta and umbilical cord immediately after the delivery of an uninfected mother, and the amniotic membrane, chorion, and the capsular membrane are separated in a benzalkonium chloride solution or a benzalkonium bromide solution. The amnion and chorion were separated from the fetal membrane consisting of four layers, the bursa decidua and the floor decidua, and then treated with enzyme using ficin, and further subjected to ultrasonic cleaning treatment to leave the remaining epithelial layer, basement membrane layer and A purified collagen-like substance which is a sterile, virus-free, foreign-body-free and pyrogen-free substance consisting of a dense layer containing human type I, type III, type V and type XVI collagen as a main component by removing the fibroblast layer To get the film of.

【0010】本発明の撚り糸は、精製コラーゲン様物質
の1本の細長片を撚ったもの、2本以上の細長片を撚り
合わせるか或は編んだもの、或はこれらの2本以上をさ
らに撚り合わせるか或は編んだもの、または三つ編みに
編んだものなどであり、その断面形状は、略円形であっ
ても或は扁平であってもよい。撚り回数は、撚り糸から
製造された生体用人工材料や人工臓器の種類によって異
なるが、2〜20回/cmであることが好ましい。2回/
cm未満では撚りが戻るおそれがあり、20回/cmを超え
ると撚り糸が切断するおそれがあるからである。また撚
り回数は多いほど引張強度が大きく、生体内分解速度の
遅い撚り糸となる。例えば縫合糸として用いる場合は1
0回/cm以上、損傷保護材として用いる場合には5回/
cmであることが好ましい。
The twisted yarn of the present invention is obtained by twisting one elongated piece of a purified collagen-like substance, twisting or knitting two or more elongated pieces, or further combining two or more of these pieces. It may be twisted or braided, or braided, and the cross-sectional shape thereof may be substantially circular or flat. The number of twists depends on the type of bioartificial material or artificial organ produced from the twisted yarn, but is preferably 2 to 20 turns / cm. 2 times /
If it is less than cm, the twist may return, and if it exceeds 20 times / cm, the twisted yarn may be cut. The larger the number of twists, the higher the tensile strength and the slower the biodegradation rate becomes. For example, 1 when used as a suture
0 times / cm or more, 5 times / cm when used as a damage protection material
It is preferably cm.

【0011】撚り糸の径は、生体用人工材料又は人工臓
器などの用途に応じて適宜決めることができ、特に限定
されないが、例えば縫合糸として用いる場合には、通常
用いられている縫合糸の直径と同じ0.33mm(0号)
〜1.016mm(7号)が好ましい。なお断面が扁平な
撚り糸の場合には、その断面積と同じ面積の円の直径を
撚り糸の径とする。撚り糸は、乾燥するとコラーゲン様
物質間で強固に接着し、引張強度などの機械的強度に優
れたものとなり、湿潤状態にしても膨潤して柔軟性を有
するようになるものの、撚りが戻ることはなく、撚り糸
状態及び優れた機械的強度を保持する。
The diameter of the twisted thread can be appropriately determined depending on the use of the artificial material for living body or artificial organ, and is not particularly limited. For example, when it is used as a suture thread, the diameter of a suture thread which is usually used. Same as 0.33mm (No. 0)
.About.1.016 mm (No. 7) is preferable. In the case of a twisted yarn having a flat cross section, the diameter of a circle having the same area as the cross sectional area is the diameter of the twisted yarn. When the twisted yarn is dried, it firmly adheres to the collagen-like substances and becomes excellent in mechanical strength such as tensile strength. Although it becomes swollen and flexible even in a wet state, the twist does not return. No, retains the twisted state and excellent mechanical strength.

【0012】本発明の精製コラーゲン様物質の撚り糸
は、以下のようにして製造される。先ず、上記精製コラ
ーゲン様物質の膜は、エラスチンが含まれるため湿潤状
態では極めて柔軟で弾性に富み、すぐに丸まって安定し
た状態に保持することができないので、塩化ベンザルコ
ニウム溶液又は臭化ベンザルコニウム溶液中で、シワが
ないように伸ばして支持台上に載置し固定した後、乾燥
空気又は乾燥窒素ガスの気流中に保持するか、或は減圧
下に保持して精製コラーゲン様物質の表面に水滴が存在
しなくなる半乾燥状態まで乾燥する。精製コラーゲン様
物質の表面に水滴が存在すると、安定した形状を保持す
ることができず、後述する切断作業が困難になり、一方
精製コラーゲン様物質が保持する水分を完全に除去する
まで乾燥すると、剪断応力が加わると亀裂が発生し、そ
の亀裂が急速に拡大するからである。
The twisted yarn of the purified collagen-like substance of the present invention is manufactured as follows. First, since the membrane of the above-mentioned purified collagen-like substance contains elastin, it is extremely flexible and elastic in a wet state, and it cannot be rolled up and held in a stable state immediately. Therefore, a solution of benzalkonium chloride or benzamide bromide is used. In a ruconium solution, stretch it so that it does not have wrinkles, place it on a support and fix it, then keep it in a stream of dry air or dry nitrogen gas, or keep it under reduced pressure. Dry to a semi-dry state where there are no water droplets on the surface. If water droplets are present on the surface of the purified collagen-like substance, it will not be possible to maintain a stable shape, and the cutting operation described below will be difficult, while drying until the water retained by the purified collagen-like substance is completely removed, This is because when shear stress is applied, a crack is generated and the crack expands rapidly.

【0013】次に支持台上に固定した精製コラーゲン物
質をレーザー光線、熱線、無菌状態の鋭利な刃物で細長
片に切断する。次いで得られたコラーゲン様物質の細長
片に精製水を噴霧或は塗布するか又は精製水中に浸漬し
て湿潤状態にし、適度な力で引っ張りながら撚りをかけ
る。切断幅及び撚りをかける時の張力は所望の撚り糸の
径により適宜決めればよい。この時、過度に水分を吸収
させるとコラーゲン様物質は細長片の形状を保持できず
に丸まってしまうので好ましくない。コラーゲン様物質
の細長片をつなぐ場合には、コラーゲン様物質の細長片
の端部と他のコラーゲン様物質の細長片の端部を過度に
水分を吸収させて重ね合わせ、圧着しながら撚りをかけ
ればよい。次いで乾燥空気又は乾燥窒素ガスの気流中に
保持するか、或は減圧下で乾燥することにより、断面が
略円形の精製コラーゲン様物質の撚り糸が得られる。さ
らに扁平な撚り糸を製造する場合には、乾燥前の撚りを
かけた状態のコラーゲン様物質の細長片又は得られた撚
り糸に水分を吸収させて柔軟性を持たせた後、加熱しな
がらプレスして乾燥すればよい。
Next, the purified collagen material fixed on the support is cut into strips with a laser beam, heat rays and a sharp blade in a sterile condition. Then, the obtained strips of collagen-like substance are sprayed or applied with purified water, or immersed in purified water to be in a wet state, and twisted while being pulled by an appropriate force. The cutting width and the tension for twisting may be appropriately determined according to the desired diameter of the twisted yarn. At this time, if water is excessively absorbed, the collagen-like substance cannot retain the shape of the strip and is curled, which is not preferable. When connecting the strips of collagen-like substance, overlap the ends of the strips of collagen-like substance with the ends of the strips of other collagen-like substances by absorbing excessive moisture, and twist them while crimping. Good. Then, the yarn is maintained in a stream of dry air or dry nitrogen gas, or is dried under reduced pressure to obtain a twisted yarn of a purified collagen-like substance having a substantially circular cross section. In the case of producing a flat twisted yarn, the strips of the collagen-like substance in a twisted state before drying or the obtained twisted yarn are made to absorb moisture to have flexibility, and then pressed while being heated. And dry it.

【0014】本発明の成形体は、上記精製コラーゲン様
物質の撚り糸から製造された平織りや綾織などの織物、
編み物、メッシュシートなどの孔又は隙間を有するシー
ト状成形体;棒などを芯材として撚り糸を円筒状に織成
し、編成し、或は螺旋状に巻きつけた孔又は隙間を有す
るチューブ状成形体;孔又は隙間を有するシート状成形
体の片面又は両面に、或は孔又は隙間を有するチューブ
状成形体の内面及び/または外面に、上記精製コラーゲ
ン様物質の膜を積層し、必要に応じてゼラチン溶液又は
コラーゲン溶液などの接着剤でこれらを一体に固着させ
た孔又は隙間のないシート状又はチューブ状成形体であ
る。上記孔又は隙間を有するシート状又はチューブ状成
形体の孔及び隙間の大きさは、成形体が用いられる生体
用人工材料や人工臓器により異なるので特に限定される
ものではない。
The molded article of the present invention is a woven fabric such as a plain weave or a twill weave produced from a twisted yarn of the above purified collagen-like substance,
A sheet-shaped molded product having holes or gaps such as a knitted fabric or a mesh sheet; a tubular molded product having holes or gaps formed by weaving a twisted yarn in a cylindrical shape with a rod or the like as a core material, knitting, or spirally winding; A film of the above-mentioned purified collagen-like substance is laminated on one surface or both surfaces of the sheet-shaped molded product having pores or gaps, or on the inner surface and / or the outer surface of the tubular molded product having pores or gaps, and if necessary gelatin. It is a sheet-shaped or tube-shaped molded body having no holes or gaps, which are integrally fixed with an adhesive such as a solution or a collagen solution. The sizes of the holes and the gaps of the sheet-shaped or tube-shaped molded product having the above-mentioned holes or gaps are not particularly limited because they vary depending on the bioartificial material or artificial organ in which the molded product is used.

【0015】上記接着剤のゼラチン溶液の原料となるゼ
ラチンとしては、一般の医療用精製ゼラチンを用いるこ
とができ、コラーゲン溶液の原料となるコラーゲンとし
てはヒト由来のコラーゲンを用いる。ゼラチン溶液の濃
度は1.0〜5.0重量%、好ましくは2.0〜3.0
重量%、コラーゲン溶液の濃度は0.001〜3.0重
量%、好ましくは0.002〜3.0重量%である。
As the gelatin used as the raw material of the gelatin solution of the adhesive, general medical purified gelatin can be used, and as the collagen used as the raw material of the collagen solution, human-derived collagen is used. The concentration of the gelatin solution is 1.0 to 5.0% by weight, preferably 2.0 to 3.0.
The concentration of the collagen solution by weight is 0.001 to 3.0% by weight, preferably 0.002 to 3.0% by weight.

【0016】本発明の成形体は、以下のようにして製造
される。孔又は隙間を有するシート状又はチューブ状成
形体の製造方法は、先ず上記乾燥精製コラーゲン様物質
の撚り糸に、精製水を噴霧或は塗布するか又は精製水中
に浸漬して水分を吸収させて柔軟性を付与し、次いで公
知の方法によりシート状に平織りや綾織に織成し、編成
し、又はメッシュシートとするか、或は棒などの芯材の
周囲に撚り糸を円筒状に織成して織物とし、編成して編
み物とし、メッシュとし、又は螺旋状に巻きつけた後、
乾燥空気又は乾燥窒素ガスの気流中に保持するか或は減
圧下で乾燥する。
The molded product of the present invention is manufactured as follows. The method for producing a sheet-shaped or tube-shaped molded product having pores or gaps is as follows. First, the twisted yarn of the above-mentioned dried and purified collagen-like substance is sprayed or applied with purified water, or immersed in purified water to absorb water and soften. Property, and then woven in a sheet form into a plain weave or a twill weave by a known method, knitted, or made into a mesh sheet, or woven by twisting a twisted yarn in a cylindrical shape around a core material such as a rod into a woven fabric, and knitting. After knitting, making a mesh, or winding it in a spiral,
It is kept in a stream of dry air or dry nitrogen gas or dried under reduced pressure.

【0017】孔又は隙間のないシート状又はチューブ状
成形体の製造方法は、上記孔又は隙間を有するシート状
又はチューブ状成形体の表面に、必要に応じて上記接着
剤を塗布もしくはこれらの成形体を上記接着剤中に浸漬
した後、上記精製コラーゲン様物質の膜を、孔又は隙間
を有するシート状成形体の片面又は両面に、或は孔又は
隙間を有するチューブ状成形体の内面及び/または外面
に積層し、次いで上記乾燥条件で乾燥する。なお孔又は
隙間を有するシート状又はチューブ状成形体と精製コラ
ーゲン様物質の膜は乾燥すると接着するが、接着が不充
分な場合には、必要に応じてこれらの成形体の表面に上
記接着剤を塗布もしくはこれらの成形体を上記接着剤中
に浸漬した後、精製コラーゲン様物質の膜を積層し、乾
燥してもよい。
The sheet-shaped or tube-shaped molded product having no holes or gaps can be produced by applying the above-mentioned adhesive to the surface of the sheet-shaped or tube-shaped molded product having the above-mentioned holes or gaps, or molding these, if necessary. After immersing the body in the adhesive, a film of the purified collagen-like substance is provided on one or both sides of the sheet-shaped molded product having pores or gaps, or on the inner surface of the tubular molded product having pores or gaps and / or Alternatively, it is laminated on the outer surface and then dried under the above drying conditions. It should be noted that the sheet-shaped or tube-shaped molded product having pores or gaps and the film of the purified collagen-like substance adhere to each other when dried, but if the adhesion is insufficient, the above-mentioned adhesive is applied to the surface of these molded products as necessary. After coating or immersing these molded bodies in the adhesive, a film of purified collagen-like substance may be laminated and dried.

【0018】本発明の精製コラーゲン様物質からなる撚
り糸及びこの撚り糸から製造された成形体は、精製コラ
ーゲン様物質の生体内分解性を制御し、かつ接着剤によ
り互いに接着した精製コラーゲン様物質の織物、編み
物、メッシュシートなどと精製コラーゲン様物質の膜を
一体に固着化するために、架橋処理を施す。特にコラー
ゲン分子中の全てのアミノ基を架橋反応させると撚り糸
及びこの撚り糸から製造された成形体を、全く抗原性が
なくかつ生体内非分解吸収性とすることができる。
The twisted yarn composed of the purified collagen-like substance of the present invention and the molded article produced from the twisted yarn are the woven fabric of the purified collagen-like substance which controls the biodegradability of the purified collagen-like substance and is adhered to each other with an adhesive. A cross-linking treatment is performed to integrally fix the knitted fabric, mesh sheet, etc. and the film of the purified collagen-like substance. In particular, when all the amino groups in the collagen molecule are subjected to a crosslinking reaction, the twisted yarn and the molded article produced from this twisted yarn can be made completely free of antigenicity and non-degradable and absorbable in vivo.

【0019】架橋処理としては、グルタールアルデヒド
架橋、熱架橋、又はガンマ線照射、電子線照射、紫外線
照射による架橋がある。グルタールアルデヒド架橋は、
濃度0.03〜3.0重量%、好ましくは0.05〜
2.0%重量のグルタールアルデヒド溶液に浸漬した後
風乾すればよい。濃度が0.03%重量未満の場合には
コラーゲン様物質が容易に剥離し、3.0%重量を超え
る場合にはコラーゲン様物質が硬化し生体親和性を失う
からである。なおグルタールアルデヒド架橋は、コラー
ゲン分子中のアミノ基とグルタールアルデヒドのアルデ
ヒド基とが反応して進行するものと考えられる。
Examples of the cross-linking treatment include glutaraldehyde cross-linking, thermal cross-linking, cross-linking by gamma ray irradiation, electron beam irradiation, and ultraviolet ray irradiation. Glutaraldehyde cross-linking
Concentration 0.03 to 3.0% by weight, preferably 0.05 to
It may be soaked in a 2.0% by weight glutaraldehyde solution and then air dried. This is because when the concentration is less than 0.03% by weight, the collagen-like substance is easily peeled off, and when it exceeds 3.0% by weight, the collagen-like substance is hardened and loses biocompatibility. It is considered that the glutaraldehyde cross-linking proceeds when the amino group in the collagen molecule reacts with the aldehyde group of glutaraldehyde.

【0020】熱架橋は、真空中で、90〜200℃、好
ましくは105〜150℃に加熱し脱水して架橋すれば
よい。加熱時間は、加熱温度、減圧度、所望する架橋度
などにより適宜調整されるが、通常6〜24時間程度で
ある。なおコラーゲンの熱架橋は、主として、コラーゲ
ン分子中の糖鎖や酸化により生じたアルデヒド基とコラ
ーゲン分子中のリジンやヒドロキシリジンなどとのシッ
フ塩基形成、アルドール縮合などにより進行すると考え
られる。
The thermal crosslinking may be carried out by heating in vacuum to 90 to 200 ° C., preferably 105 to 150 ° C., dehydration and crosslinking. The heating time is appropriately adjusted depending on the heating temperature, the degree of pressure reduction, the desired degree of crosslinking, etc., but is usually about 6 to 24 hours. It is considered that the thermal cross-linking of collagen mainly proceeds by Schiff base formation, aldol condensation or the like between sugar chains in the collagen molecule or aldehyde groups generated by oxidation and lysine or hydroxylysine in the collagen molecule.

【0021】ガンマー線、電子線、紫外線などの照射に
よる架橋は、湿度75%以上の雰囲気下で行う。湿度が
75%未満の湿度でガンマー線、電子線、紫外線などを
照射する場合には、精製コラーゲン様物質が分解するか
らである。また精製コラーゲン様物質の含有水分は、そ
の線量にもよるが20%以上にする。含有水分量が、2
0%未満の場合にはコラーゲン様物質の分解が架橋より
も優先するからである。電子線及び放射線の照射量は、
1×106 〜1×107 レントゲンが好ましい。106
レントゲン未満になると精製コラーゲン様物質の架橋が
不充分となり、107 レントゲンを超えると精製コラー
ゲン様物質の分解が多くなるからである。紫外線の照射
量は、照射距離及び照射出力により決まるが、おおむね
4ワットの紫外線燈で10cmの距離から1.5時間の照
射が好ましい。
Crosslinking by irradiation with gamma rays, electron beams, ultraviolet rays, etc. is carried out in an atmosphere having a humidity of 75% or more. This is because the purified collagen-like substance is decomposed when gamma rays, electron beams, ultraviolet rays, etc. are irradiated at a humidity of less than 75%. The water content of the purified collagen-like substance should be 20% or more, depending on the dose. Water content is 2
When it is less than 0%, the decomposition of the collagen-like substance has priority over the crosslinking. The dose of electron beam and radiation is
1 × 10 6 to 1 × 10 7 roentgen is preferable. 10 6
This is because if it is less than roentgen, the cross-linking of the purified collagen-like substance is insufficient, and if it exceeds 10 7 roentgen, the purified collagen-like substance is decomposed much. The irradiation amount of ultraviolet rays is determined by the irradiation distance and the irradiation output, but irradiation with an ultraviolet lamp of approximately 4 watts from a distance of 10 cm for 1.5 hours is preferable.

【0022】さらに本発明の撚り糸及び撚り糸から製造
された成形体は、抗凝血性及び溶血性を付与し抗原性を
除去するためにサクシニル化処理を施すことができる。
サクシニル化は、コラーゲン分子中の残りの大部分のア
ミノ基を無水コハク酸と反応させるものである。このサ
クシニル化は通常行われている方法でよく、例えば、
0.02M ホウ酸緩衝液(pH9.0)250mlと5%無
水コハク酸アセトン溶液50mlとの混合液に、1〜48
時間、好ましくは12〜24時間浸漬後、水洗し、次い
で減圧乾燥すればよい。なおコラーゲン様物質がサクシ
ニル化されていることを確認するためには、サクシニル
化された撚り糸及び成形体を、0.33重量%のニンヒ
ドリン水溶液に3〜5分間浸漬すればよい。ニンヒドリ
ンの発色反応は、コラーゲン中のアミノ基とニンヒドリ
ンが反応して生じる縮合生成物に基づくものであるの
で、サクシニル化されるほど、コラーゲン様膜は染色さ
れ難くなる。
Further, the twisted yarn of the present invention and the molded product produced from the twisted yarn can be subjected to succinylation treatment in order to impart anticoagulant property and hemolytic property and remove antigenicity.
Succinylation causes most of the remaining amino groups in the collagen molecule to react with succinic anhydride. This succinylation may be performed by a commonly used method, for example,
1 to 48 of a mixture of 250 ml of 0.02M borate buffer (pH 9.0) and 50 ml of 5% acetone solution of succinic anhydride.
After dipping for a time, preferably 12 to 24 hours, it may be washed with water and then dried under reduced pressure. In order to confirm that the collagen-like substance is succinylated, the succinylated twisted yarn and the molded body may be immersed in a 0.33 wt% ninhydrin aqueous solution for 3 to 5 minutes. Since the color reaction of ninhydrin is based on the condensation product generated by the reaction between the amino group in collagen and ninhydrin, the more succinylated, the less likely the collagen-like membrane is stained.

【0023】以上の工程により製造された本発明の精製
コラーゲン様物質の撚り糸は、縫合糸などに適用するこ
とができ、さらに撚り糸から製造された成形体は、生体
内に埋設される創傷保護材、創傷補填材、創傷補綴材、
癒着防止材などの生体用人工材料又は人工血管、人工気
管、人工食道、人工尿道、人工尿管、人工皮膚などの人
工臓器などに応用することができる。
The twisted yarn of the purified collagen-like substance of the present invention produced by the above steps can be applied to sutures and the like, and the molded article produced from the twisted yarn is a wound protection material embedded in a living body. , Wound prosthesis, wound prosthesis,
It can be applied to artificial materials for living organisms such as anti-adhesion materials or artificial blood vessels, artificial trachea, artificial esophagus, artificial urethra, artificial ureters, artificial organs such as artificial skin, and the like.

【0024】[0024]

【実施例】次に、本発明を実施例に基づいてより詳細に
説明する。 実施例1精製コラーゲン様物質の製造 肝炎、HIV等のウィルスや性病等の病原菌に感染して
いないことを確認した産婦から、分娩直後に排泄された
胎児膜、胎盤、臍帯から鋭利な刃物を用いて胎児膜のみ
を切除・分離し、直ちに2リットルの0.1%日本薬局
方・塩化ベンザルコニウム液中に浸漬した後、日本薬局
方・生理食塩水の流水中で胎児膜に付着する血液を十分
に洗浄、除去し、得られた胎児膜を2リットルの新しい
0.1%日本薬局方・塩化ベンザルコニウム液中に浸漬
した。得られた胎児膜は、羊膜、絨毛膜、被包脱落膜お
よび床壁脱落膜の4層からなる略円筒状であった。次い
で新しい0.1%塩化ベンザルコニウム液中で、鋭利な
刃物を用いて円筒状の胎児膜を切開して平面状とした
後、10リットルの新しい0.1%日本薬局方・塩化ベ
ンザルコニウム液中で静かに濯ぐように揺り動かして羊
膜を剥離、分離した。絨毛膜は残部膜から殆どが剥離し
た状態であったので、指で残部膜から絨毛膜を完全に剥
離、分離した。分離した羊膜及び絨毛膜を別の新しい
0.1%塩化ベンザルコニウムに浸漬した。
EXAMPLES Next, the present invention will be described in more detail based on examples. Example 1 Production of Purified Collagen-Like Substance Using a sharp knife from the fetal membrane, placenta, and umbilical cord excreted immediately after delivery from a mother confirmed to have not been infected with pathogens such as hepatitis, virus such as HIV, and sexually transmitted diseases. Blood that adheres to the fetal membrane in the running water of physiological saline of Japan Pharmacopeia after being immersed in 2 liters of 0.1% Japanese Pharmacopoeia / benzalkonium chloride solution immediately after removing and separating only the fetal membrane Was thoroughly washed and removed, and the obtained fetal membrane was immersed in 2 liters of a new 0.1% Japanese Pharmacopoeia benzalkonium chloride solution. The fetal membrane obtained was in a substantially cylindrical shape consisting of four layers of amniotic membrane, chorion, encapsulating decidua and floor wall decidua. Then, in a new 0.1% benzalkonium chloride solution, a cylindrical fetal membrane was incised with a sharp blade to make it flat, and then 10 liters of a new 0.1% Japanese Pharmacopoeia benzalcochloride. The amniotic membrane was peeled and separated by gently shaking it in a nitric acid solution so as to shake it. Most of the chorion was peeled from the residual membrane, so the chorion was completely peeled and separated from the residual membrane with a finger. The separated amnion and chorion were immersed in another fresh 0.1% benzalkonium chloride.

【0025】次いで高密度ポリエチレン製の作業台上
に、上記方法により得られた羊膜を延伸展開した後、無
菌・医療用ポリプロピレン製の枠2枚を用いて作業台上
に固定し、無菌・パイロジェンフリーの流水中で、60
分間超音波洗浄(周波数20〜50kHz )を行った。次
いで超音波洗浄した羊膜を、2%のNaN3 を溶解した
0.01%フィシンのpH7.4、0.2M のリン酸緩衝
液(フィシン調整液)中に、室温で24時間浸漬した。
フィシン処理後の羊膜を、60分間再度超音波洗浄(周
波数20〜50KHz )を行った。羊膜の重量は、2回の
超音波洗浄前と比較して23%減量した。2回の超音波
洗浄により羊膜は、羊膜に付着した生体組織由来の物質
やヒト羊膜基質物質であるコラーゲン様膜の表層の一部
が除去されて、ヒト羊膜の緻密層からなる精製コラーゲ
ン様物質の膜が得られた。この精製コラーゲン様物質
は、日本薬局方の無菌試験法、発熱性物質試験法及び人
工血管製造承認基準で定めた異物観察試験法などの試験
をした結果、無菌、発熱物質及び異物がないことを確認
した。
Then, the amniotic membrane obtained by the above method was stretched and developed on a work bench made of high-density polyethylene, and then fixed on the work bench using two frames of sterile polypropylene for medical use, and aseptic pyrogen. 60 in free running water
Ultrasonic cleaning (frequency 20 to 50 kHz) was performed for a minute. Then, the ultrasonically washed amniotic membrane was immersed in a 0.01% ficin pH 7.4, 0.2M phosphate buffer solution (Ficin preparation solution) in which 2% NaN 3 was dissolved at room temperature for 24 hours.
The amniotic membrane after the ficin treatment was subjected to ultrasonic cleaning (frequency 20 to 50 kHz) again for 60 minutes. The weight of the amniotic membrane was reduced by 23% as compared with before the two ultrasonic cleanings. The amniotic membrane is a purified collagen-like substance composed of a dense layer of human amniotic membrane, which is obtained by removing the part of the surface layer of the collagen-like membrane that is a substance derived from living tissue or a human amniotic membrane substrate substance attached to the amniotic membrane by two ultrasonic cleanings. A film of was obtained. This purified collagen-like substance was tested for sterility, pyrogen test method, foreign body observation test method, etc. defined in the approval criteria for artificial blood vessel production of the Japanese Pharmacopoeia, and as a result, it was confirmed that there is no sterility, pyrogen and foreign material. confirmed.

【0026】断面が略円形の撚り糸の製造 次に得られた精製コラーゲン様物質を無菌ブース内で3
0℃の無菌の空気気流中に72時間放置して表面に水滴
が存在しなくなるまで乾燥した。次いで半乾燥状態の得
られた精製コラーゲン様物質を無菌状態の鋭利な刃物で
切断して、幅1cm、長さ15cmの精製コラーゲン様物質
の細長片とした。次に得られた精製コラーゲン様物質の
細長片に精製水を1分間噴霧して湿潤状態にした後、枠
から外し、1本の細長片に撚りをかけて撚り糸とし、先
端部10mmは他のコラーゲン様膜を重ね合わせて撚りを
かけて、直径2mm、長さ54cmの断面が略円形の撚り糸
を製造した。撚り糸の撚り数は5回/cmであった。次い
で60℃の無菌の気流中で3分間乾燥して精製コラーゲ
ン様物質の撚り糸を製造した。得られた撚り糸は、引張
強度などの機械的強度に優れ、剛直な撚り糸であった。
湿潤状態にしても撚りは戻らず、かつ優れた機械的強度
を有していた。
Manufacture of a twisted yarn having a substantially circular cross section . The purified collagen-like substance obtained next was placed in a sterile booth for 3 times.
It was left for 72 hours in a sterile air stream at 0 ° C. and dried until there were no water droplets on the surface. Then, the obtained purified collagen-like substance in a semi-dried state was cut with a sharp blade in a sterile state to obtain a strip of the purified collagen-like substance having a width of 1 cm and a length of 15 cm. Next, purified water is sprayed onto the obtained strips of the purified collagen-like substance for 1 minute so as to be in a wet state, then removed from the frame, and one strip is twisted to form a twisted yarn. Collagen-like membranes were overlapped and twisted to produce a twisted yarn having a diameter of 2 mm and a length of 54 cm, which had a substantially circular cross section. The number of twists of the twisted yarn was 5 times / cm. Then, it was dried in a sterile air stream at 60 ° C. for 3 minutes to produce a yarn of purified collagen-like substance. The obtained twisted yarn was excellent in mechanical strength such as tensile strength and was a rigid twisted yarn.
The twist did not return even in the wet state, and it had excellent mechanical strength.

【0027】断面が扁平な撚り糸の製造 また上記撚り糸に精製水を噴霧して湿潤状態にした後、
130℃に加熱しながらプレスした後、60℃の無菌の
気流中で3分間乾燥して扁平状の精製コラーゲン様物質
からなる撚り糸を製造した。得られた撚り糸は、断面が
略円形状の撚り糸と同様に引張強度などの機械的強度に
優れ、剛直な撚り糸であった。湿潤状態にしても撚りが
戻らず、かつ優れた機械的強度を有していた。
Manufacture of a twisted yarn having a flat cross section Further, after the above twisted yarn is sprayed with purified water to make it wet,
After pressing while heating to 130 ° C., it was dried in a sterile air stream at 60 ° C. for 3 minutes to produce a flat twisted yarn made of a purified collagen-like substance. The obtained twisted yarn was excellent in mechanical strength such as tensile strength like the twisted yarn having a substantially circular cross section, and was a rigid twisted yarn. The twist did not return even in a wet state, and it had excellent mechanical strength.

【0028】孔のないシート状成形体の製造 得られた断面が略円形状の撚り糸を、30℃の水を10
分間噴霧して軟化させた後、平織りの織布に織成した。
得られた平均孔径2mmの織布(10cm×10cm)に、
0.002重量%コラーゲン水溶液を塗布した後、上記
精製コラーゲン様物質(10cm×10cm)の膜を貼り合
わ、それをさらに37℃の乾燥温風下で24時間乾燥し
た。次いでこれを0.05重量%のグルタールアルデヒ
ド水溶液中に10分間浸漬、静置した後、精製水を用い
て未反応のグルタールアルデヒド溶液を洗浄、除去し
た。得られたシートを0.33重量%のニンヒドリン水
溶液に浸漬して、コラーゲン中のアミノ基が残存し、サ
クシニル化できる余地が残っていることを確認した。
Manufacture of a sheet-shaped molded product having no pores The obtained twisted yarn having a substantially circular cross section is treated with water at 30 ° C. for 10 times.
After spraying for a minute to soften the fabric, it was woven into a plain weave fabric.
On the obtained woven fabric (10 cm x 10 cm) having an average pore diameter of 2 mm,
After applying a 0.002% by weight collagen aqueous solution, a film of the above-mentioned purified collagen-like substance (10 cm × 10 cm) was attached, and it was further dried for 24 hours under hot dry air at 37 ° C. Next, this was immersed in a 0.05% by weight aqueous solution of glutaraldehyde for 10 minutes and allowed to stand, and then unreacted glutaraldehyde solution was washed and removed using purified water. The obtained sheet was immersed in a 0.33 wt% ninhydrin aqueous solution, and it was confirmed that the amino groups in collagen remained and there was room for succinylation.

【0029】隙間のあるチューブ状成形体の製造 直径5mmの医療用ポリプロピレンの棒の表面に、日本薬
局方・グリセリンを塗布し、30℃の水を噴霧しなが
ら、その棒を芯として断面が略円形の上記撚り糸を1mm
の隙間をあけて巻きつけた後、60℃の無菌の気流中で
5分間乾燥し、芯を抜き取って、内径5mm、厚み2mm、
隙間1mmの隙間を有するチューブ状成形体を得た。
Manufacture of a tubular molded article with a gap The surface of a medical polypropylene rod having a diameter of 5 mm was coated with Japanese Pharmacopoeia glycerin and sprayed with water at 30 ° C., and the cross section was made substantially with the rod as a core. 1mm of the above round yarn
After wrapping with a gap between them, it is dried in a sterile air stream at 60 ° C for 5 minutes, the core is removed, and the inner diameter is 5 mm, the thickness is 2 mm,
A tubular molded body having a gap of 1 mm was obtained.

【0030】隙間のないチューブ状成形体の製造 上記した方法で製造した孔のないシート状成形体を無菌
状態の鋭利な刃物で切断して5mm幅の細長片とし、この
細長片を上記した隙間のあるチューブ状成形体の製造方
法と同様にして芯に巻きつけた後乾燥して、内径5mm、
厚み2mmの隙間のないチューブ状成形体を得た。
Manufacture of tube-shaped molded product having no gap The sheet-shaped molded product having no hole produced by the above-mentioned method is cut with a sharp blade in an aseptic state to obtain a strip having a width of 5 mm, and the strip is provided with the above-mentioned gap. In the same manner as in the method for producing a tubular molded body having
A tubular molded body having a thickness of 2 mm and having no gap was obtained.

【0031】生体適合性の向上 前記方法で製造した、断面が円形状の撚り糸、断面が扁
平な撚り糸、孔のないシート状成形体、隙間のあるチュ
ーブ状成形体及び隙間のないチューブ状成形体を、0.
02M 、pH9.0のホウ酸緩衝液500mlと5%無水コ
ハク酸アセトン溶液100mlの混合溶液中に4〜8時間
浸漬してサクシニル化処理を施した。サクシニル化され
た材料を、0.33%のニンヒドリン水溶液に浸漬し
て、コラーゲン中に残存のアミノ基がないこと(生体適
合性が向上したこと)を確認した。
Improvement of biocompatibility A twisted yarn having a circular cross section, a twisted yarn having a flat cross section, a sheet-shaped molded product having no holes, a tube-shaped molded product having a gap and a tube-shaped molded product having no gap produced by the above method. To 0.
A succinylation treatment was carried out by immersing in a mixed solution of 500 ml of a borate buffer solution of 02M, pH 9.0 and 100 ml of a 5% acetone succinic anhydride solution for 4 to 8 hours. The succinylated material was immersed in a 0.33% aqueous ninhydrin solution to confirm that there were no residual amino groups in the collagen (improved biocompatibility).

【0032】滅菌 上記方法で製造した、断面が略円形の撚り糸、断面が扁
平な撚り糸、孔のないシート状成形体、隙間のあるチュ
ーブ状成形体及び隙間のないチューブ状成形体を、酸化
エチレンガス20%と炭酸ガス80%の混合ガスを用
い、50℃、湿度40%の条件で7時間滅菌した。また
2.0メガラドのガンマー線を照射して滅菌した。滅菌
後、日本薬局方の無菌試験法、発熱性物質試験法に従っ
て試験した結果、全ての撚り糸及び成形体に物性の変化
はなく、無菌であり、発熱性物質がないことを確認し
た。
Sterilization A twisted yarn having a substantially circular cross section, a twisted yarn having a flat cross section, a sheet-shaped molded product having no pores, a tubular molded product having a gap and a tubular molded product having no gap produced by the above-mentioned method are treated with ethylene oxide. Using a mixed gas of 20% gas and 80% carbon dioxide gas, it was sterilized for 7 hours under the conditions of 50 ° C. and 40% humidity. It was also sterilized by irradiation with 2.0 megarads of gamma rays. After sterilization, as a result of testing according to the Japanese Pharmacopoeia sterility test method and pyrogen test method, it was confirmed that all the twisted yarns and molded articles had no change in physical properties, were sterile, and had no pyrogen.

【0033】[0033]

【発明の効果】本発明の撚り糸は、乾燥すると精製コラ
ーゲン様物質間で強固に接着し、湿潤状態にして柔軟性
を持たせても撚りが戻ることはない。撚り糸及び成形体
は、生体適合性、引張強度などの機械的強度に優れ、適
用後生体内での分解に伴って経時的にヒト生体患部の組
織や臓器と置換して、縫合部、疾患部又は損傷部が自己
の臓器や組織で修復することを促進・補助し、自己修復
が完了後は生体内から分解、代謝、排泄される。また架
橋処理により架橋度を調整して、生体内分解性を所望の
条件に制御することができる。さらにサクシニル化によ
り抗凝血性及び溶血性が付与できる。成形体は、機械的
強度の優れた本発明の撚り糸を用いて製造されているの
で、合成高分子材料などの補強材を用いなくても機械的
強度に優れている。したがって、縫合糸、創傷保護材、
創傷補填材、創傷補綴材、癒着防止材などの生体用人工
材料又は人工血管、人工気管、人工食道、人工尿道、人
工尿管、人工皮膚などの人工臓器などに適用することが
できる。
EFFECTS OF THE INVENTION When the twisted yarn of the present invention is dried, it firmly adheres to the purified collagen-like substance, and even if it is made wet to have flexibility, the twist does not return. Twisted yarns and molded articles are excellent in biocompatibility, mechanical strength such as tensile strength, and are replaced with tissues or organs of a human body affected area over time due to decomposition in vivo after application, and sutured portions, diseased portions or It promotes and assists the damaged area to repair with its own organs and tissues, and is decomposed, metabolized, and excreted from the body after completion of self-repair. Further, the degree of cross-linking can be adjusted by the cross-linking treatment to control the biodegradability to desired conditions. Furthermore, succinylation can impart anticoagulant and hemolytic properties. Since the molded product is manufactured using the twisted yarn of the present invention having excellent mechanical strength, it has excellent mechanical strength without using a reinforcing material such as a synthetic polymer material. Therefore, sutures, wound protectors,
The present invention can be applied to artificial materials for living bodies such as wound filling materials, wound prosthesis materials, and adhesion preventing materials, or artificial blood vessels, artificial trachea, artificial esophagus, artificial urethra, artificial ureters, artificial organs such as artificial skin, and the like.

Claims (6)

【特許請求の範囲】[Claims] 【請求項1】 ヒト羊膜又はヒト絨毛膜から得られた精
製コラーゲン様物質の細長片に撚りをかけた撚り糸。
1. A twisted yarn obtained by twisting a strip of a purified collagen-like substance obtained from human amnion or human chorion.
【請求項2】 ヒト羊膜又はヒト絨毛膜から得られた湿
潤状態の精製コラーゲン様物質の細長片を乾燥しながら
撚り、必要に応じて架橋処理及び/またはサクシニル化
処理を施すことを特徴とする撚り糸の製造方法。
2. A strip of a purified collagen-like substance in a wet state obtained from human amniotic membrane or human chorion is twisted while being dried, and is optionally subjected to a crosslinking treatment and / or a succinylation treatment. Manufacturing method of twisted yarn.
【請求項3】 請求項1に記載の撚り糸をシート状又は
チューブ状に成形した成形体。
3. A molded product obtained by molding the twisted yarn according to claim 1 into a sheet shape or a tube shape.
【請求項4】 請求項1に記載の撚り糸を湿潤状態にし
た後、シート状又はチューブ状に成形し、次いで必要に
応じて架橋処理及び/またはサクシニル化処理を施した
後、乾燥することを特徴とする成形体の製造方法。
4. A method in which the twisted yarn according to claim 1 is moistened, shaped into a sheet or a tube, and optionally crosslinked and / or succinylated, and then dried. A method for manufacturing a featured molded article.
【請求項5】 請求項1に記載の撚り糸をシート状又は
チューブ状に成形した成形体の表面に、ヒト羊膜又はヒ
ト絨毛膜から得られた精製コラーゲン様物質の膜を積層
した成形体。
5. A molded product obtained by laminating a film of a purified collagen-like substance obtained from human amnion or human chorion on the surface of the molded product obtained by molding the twisted yarn according to claim 1 into a sheet or tube.
【請求項6】 請求項1に記載の撚り糸をシート状又は
チューブ状に成形した成形体の表面に、ヒト羊膜又はヒ
ト絨毛膜から得られた精製コラーゲン様物質の膜を積層
した後、必要に応じて架橋処理及び/またはサクシニル
化処理を施した後、乾燥することを特徴とする成形体の
製造方法。
6. A layer of purified collagen-like substance obtained from human amniotic membrane or human chorion is laminated on the surface of a molded body obtained by molding the twisted yarn according to claim 1 into a sheet or tube, and then, if necessary. A method for producing a molded article, which comprises subjecting the material to a crosslinking treatment and / or a succinylation treatment, and then drying.
JP6011715A 1994-02-03 1994-02-03 Twisted yarn of purified collagen-like substance, formed body of twisted yarn and their manufacture Pending JPH07213597A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP6011715A JPH07213597A (en) 1994-02-03 1994-02-03 Twisted yarn of purified collagen-like substance, formed body of twisted yarn and their manufacture

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP6011715A JPH07213597A (en) 1994-02-03 1994-02-03 Twisted yarn of purified collagen-like substance, formed body of twisted yarn and their manufacture

Publications (1)

Publication Number Publication Date
JPH07213597A true JPH07213597A (en) 1995-08-15

Family

ID=11785745

Family Applications (1)

Application Number Title Priority Date Filing Date
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Country Status (1)

Country Link
JP (1) JPH07213597A (en)

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