JP3534408B2 - 流動化腸粘膜下組織および注射可能な組織移植体としてのその使用 - Google Patents
流動化腸粘膜下組織および注射可能な組織移植体としてのその使用Info
- Publication number
- JP3534408B2 JP3534408B2 JP51232594A JP51232594A JP3534408B2 JP 3534408 B2 JP3534408 B2 JP 3534408B2 JP 51232594 A JP51232594 A JP 51232594A JP 51232594 A JP51232594 A JP 51232594A JP 3534408 B2 JP3534408 B2 JP 3534408B2
- Authority
- JP
- Japan
- Prior art keywords
- intestinal
- tissue
- submucosa
- mucosa
- composition
- 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.)
- Expired - Lifetime
Links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3695—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this
-
- A—HUMAN NECESSITIES
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- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
-
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/37—Digestive system
- A61K35/38—Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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-
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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-
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
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-
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
- A61L27/367—Muscle tissue, e.g. sphincter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
-
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3691—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
-
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A61F2002/2835—Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
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- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
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- A—HUMAN NECESSITIES
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Description
と使用のための方法に関する。より詳細には本発明は、
腸粘膜下組織から得た注射可能で免疫原性のない組織移
植組成物に関する。生体内において組織欠陥を有する部
位に処置を行うにあたり、本発明による流動化組織移植
組成物は、欠陥を修復する内在性組織の成長を促進させ
る。
する組成物をシート状に形成したものを組織移植材料と
して用い得るという報告がある。米国特許第4902508号
を参照されたい。この米国特許に記載され請求されてい
る好ましい三層構造シート用組成物は、高応諾性、高破
断点および効果的な有孔指数を有するなど、優れた機械
的性質を示すため、血管への移植構造体として用いられ
その利便性を発揮している。当該技術に開示された移植
材料はまた、腱やじん帯の代替物としての応用分野にお
いても有用である。これらの分野で用いる場合には、上
記三層構造の移植構成体の好ましいものは、移植構成体
で置換された組織を再成長させるためのマトリックスと
して機能するものと思われる。この性質は、腸組織由来
の移植構成体がユニークな三層シート構造を取っている
ことによるものと信じられていた。
び/またはプロテアーゼ分解することによって見かけの
生体親和性を低下させることなく流動化させることがで
き、修復が必要なホストの組織に対しより非侵襲的な投
与方法(例えば注射あるいは外用)に用い得ることが見
いだされた。
供するものである。本発明の一態様においては、上記組
成物は粉砕された大小の腸粘膜下組織を好ましくは水性
懸濁液中において含有するものである。本発明は、別の
観点からは、プロテアーゼ分解された腸粘膜下組織を含
有する組成物を提供するものである。
合組織などの軟組織および骨を含む内在性組織を形成さ
れる方法に有利に用いられる。この方法は、粉砕された
腸粘膜下組織やそのプロテアーゼ分解物の懸濁液を含有
する組成物を脊椎動物に注射する段階を包含するもので
あって、その注射の量は、前記流動化組織移植組成物が
注射された場所において内在性の組織成長を誘導するの
に充分な量をもってするものである。本発明において成
長が促進される内在性結合組織としては、コラーゲン、
エラスチン、および筋肉が挙げられる。
物の括約筋機能を増強させるための方法を提供するもの
であって、この方法は、粉砕腸粘膜下組織の水性懸濁液
を含有する組織移植組成物の有効量を括約筋形成組織に
注射する段階を包含する。本発明をさらに別の観点から
述べると、本発明は、注射可能な組成物としてプロテア
ーゼ分解された腸粘膜下組織を含有する組成物を用い
る、括約筋機能の増強方法を提供するものである。
組成物は、広範な組織修復、組織再構築という種々の応
用分野に利用できる。これらの組成物は単独であるいは
米国特許第4902308号に記載された移植材料と共に用い
ることができる。例えば本発明組成物は関節骨同士の界
面におけるコラーゲン性と半月を外科的に再構築するた
めに用い得る。そのような再構築においては、第一の組
織移植組成物のシート(これは温血脊椎動物の腸の粘膜
下組織を含有することが好ましい)が密閉された小袋の
形態に作成され、この小袋には本発明の流動化組織移植
組成物が充填される。
記載する現在認識されている発明を実施するための最良
の形態を例示する好ましい態様の詳細な説明を考慮する
ことにより、当業者にとって明白となろう。
は、温血脊椎動物の腸組織断片の粘膜下組織を粘膜基底
部とともに含有するものである。特に、好ましい出発物
質は、小腸の断片の粘膜下組織を粘膜筋板層および細胞
層とともに含んでおり、断片の粘膜の筋層および管腔部
からそれらの層が層分離される。本明細書中では、この
ような材料を“小腸粘膜下組織(“SIS")または“SIS
三層ラミネート”と呼ぶ。
詳述されており、その開示内容は本明細書の一部を構成
するものとする。まず腸の断片を長手方向の擦過運動に
よって剥離し、外側層(特に、漿膜と筋層)と内側層
(粘膜の管腔部)の両方を除去する。典型的には、SIS
を生理食塩水ですすぎ、使用するまで下記に述べるよう
に水和状態または脱水状態で保存する。
/または当該組織を可溶化しかつ実質的に均質の溶液を
形成するのに十分な時間、トリプシンまたはペプシンな
どのプロテアーゼを用いて粘膜下組織を分解することに
よって、腸粘膜下組織の溶液または懸濁液として調製す
る。腸粘膜下組織から成る出発物質は、裂断、切断、磨
砕、剪断などによって粉砕する。冷凍または凍結乾燥状
態で粘膜下組織を磨砕するのが好ましい。しかし、粘膜
下組織の破片の懸濁液を高速(高剪断)の混合器内で処
理し、もし必要であれば、過剰な水分を遠心分離するか
他の容器に移ることによって脱水しても良好な結果を得
ることができる。粉砕した腸粘膜下組織を乾燥して粘膜
下組織粉末とすることもできる。その後、それを水和、
即ち、水または緩衝化された生理食塩水、および他の任
意の薬学的に許容される賦形剤と混合し、25℃で約2cps
〜約300,000cpsの粘度を有する流体として組織移植組成
物を調製する。粘度が高い移植組成物はゲルまたはペー
ストの固さを有する。本発明の組成物は、電離放射線に
さらすなどの本技術分野で知られた殺菌技術を用いて殺
菌することができる。
野で知られたハイブリドーマの技術を使用して米国特許
第4902508号に記載された組織移植材料に対する抗体を
生産するために使用できる。SISから得た流動化粘膜下
組織を免疫的にコンピテントな動物に注射し、その動物
の脾臓内での抗体生成リンパ球の生成を引き起こす。リ
ンパ球を骨髄腫細胞と融合させハイブリッド細胞(ハイ
ブリドーマ)を形成し、粘膜下組織抗体生成能を有する
ものをスクリーニングする。選択されたハイブリドーマ
を培養することによって産生されたモノクロール抗体を
分離し、生体内および試験管内において粘膜下組織を検
出するのに使用する。
修復が必要な組織のための注射可能の異種移植として、
または、最も典型的には外傷または疾病によって引き起
こされた組織の欠陥を修復するための増強移植としても
使用できる。また、本発明の流動化粘膜下組織組成物
は、移植構造物のためのフィラーとして使用するのが有
利であり、例えば、そのフィラーは密閉された(縫合さ
れた)小袋、即ち“枕”状に形成された1個またはそれ
以上のSISのシートを含んでおり、美容外科手術または
外傷処置手術に使用される。
さみ、単刃の安全かみそり、または他の好適な切断具を
使用して任意の小片に切り刻む。底が平坦なステンレス
製の容器にサンプルを入れ、液体窒素を容器内に導入す
ることによってサンプルを冷凍し、それらを粉砕するた
めの準備を行う。
する。この様な処理は、例えば、冷凍サンプの上に置か
れた円筒状の真鍮インゴットを具備する手動式のアーバ
ープレスを用いて行われる。真鍮インゴットは、サンプ
ルとプレスのアーバーとの間の仲介物として機能する。
典型的には、液体窒素をSISサンプルに定期的に加える
ことによりサンプルを凍結状態に保つ必要がある。
に、別の方法によってSISサンプルを粉砕してもよい。
例えば、SISサンプルを凍結乾燥し、それを手動式アー
バープレスまたは他の磨砕手段を用いて磨砕することが
できる。それに替え、SISを高剪断混合器内で処理し、
脱水と乾燥を行うことによってSIS粉末を生産してもよ
い。
を磨砕することにより、均一でより微細に分割された製
品を生産できる。この場合も、必要に応じて液体窒素を
使用し、最終磨砕の間、冷凍粒子を固形の状態に維持す
る。その粉末は、例えば、緩衝化した生理食塩水を使用
して容易に水和させることができ、これにより本発明の
流動化組織移植材料を所望の粘度で生産できる。
った容器に入れる。そして、粉末をタンパク質分解し、
実質的に均一な溶液を作成する。ある例では、HClでpH
を2.5に調整した0.1Mの酢酸中において、1mg/mlのペプ
シン(シグマ・ケミカル社、ミズーリ州セントルイス)
を用いて室温下48時間かけて粉末を分解する。反応培地
を水酸化ナトリウムを用いて中和し、ペプシン活性を不
活化する。可溶化された粘膜下組織を、溶液の塩析出に
よって濃縮し、更なる精製および/または凍結乾燥のた
めに分離し、プロテアーゼによって可溶化された腸粘膜
下組織を粉末として調製する。
下組織成分の濃度と水和の程度とを制御することによっ
て操作できる。粘度は、25℃において約2cps〜約300,00
0cpsの範囲に調整できる。粘度が低い粘膜下組織組成物
は、関節内への適用または体腔内への適用に適してい
る。ゲルなどの高粘度組成物は、SIS分解溶液のpHを約
6.0〜約7.0に調整することによって調製できる。粘膜下
組織の懸濁液または粘膜下組織の分解溶液などの本発明
によるゲル組成物は、典型的には注射器またはカテーテ
ルを用いて皮下または筋肉内へ適用するのが好ましい。
用した。即ち、通常の雑種成犬の内側半月を除去し、新
たに構成したSIS半月によって置き換えた。このSIS半月
は、半円形の枕状に形成したSISのシート(細胞層を
“内部”に有する)によって構成した。この枕をSISの
懸濁液で充填し、枕の縫合線を内側側副靱帯により取り
付けた。これにより、枕の物質は、内側の大腿関節と脛
骨プラトーとの間において荷重を受ける衝撃吸収体とし
て機能した。5匹の内3匹を実験の犠牲にした。1番目
のイヌは手術後4カ月と4日が経過した時に犠牲にし
た。2番目のイヌは手術後3カ月と21日が経過した時に
犠牲にした。4番目の動物は手術後4カ月と3日が経過
した時に犠牲にした。これら3匹の動物の何れも結果は
類似していた。SIS/半月は、組織学的方法では通常の半
月の繊維軟骨と区別できない、部分的に組織化された繊
維軟骨材料を形成した。この新たに形成された半月の形
状は通常の半月とは異なるが、本研究の目的は、結合組
織の再構築(remodeling)が起きるか否か、および好ま
しくない反応が生じるか否かを見るだけであった。拒絶
反応、炎症、もしくは感染の兆候は全く無かった。3番
目と5番目のイヌはまだ生きている。上記の研究では、
ブタSISをイヌホストに使用した。
さらに、溶液(pH=8.0)を膣壁の粘膜下組織位置に、
また膝の内側側副靱帯領域に注射した。ホスト動物の拒
絶反応、感染、もしくは異常な生理学的反応の兆候はな
かった。注射した部位は肥厚する。注射物質として生理
食塩水を使用したコントロール部位では材料が完全に吸
収され、結合組織の肥厚は見られなかった。
使用した。SIS材料の懸濁液を、エンドスコピーを介し
て、またラパロスコピーを介して、ブタの膀胱の粘膜下
組織および漿膜下の位置に注射した。さらに、その材料
(約4ml)を、尿道口周囲の両側における粘膜下組織位
置および膀胱壁に注射した。最初の注射から9週間経過
した後に1匹のブタを実験の犠牲にした。平滑筋運動が
陽性である、紡錘体形の筋繊維芽細胞の浸潤を伴った結
合組織の再構築を示した。この種の結合組織反応は、動
脈位置におけるSISチューブを使用した場合に見られた
ものと非常に類似している。注射物質として生理食塩水
を使用したコントロール位置では反応が見られなかっ
た。SISは、適切な結合組織の再構築を促進し、懸濁し
たSIS材料を用いることによって膀胱壁および/または
膀胱括約筋を増強できると結論づけられる。
び修復の両面において広範な用途がある。欠陥が存在す
る領域内において生来の結合組織または骨の再成長を誘
発するために、流動化粘膜下組織組成物を本発明の方法
に従って使用する。治癒すべき組織欠陥または負傷の在
る場所に有効量の粘膜下組織組成物を注射することによ
り、より侵襲的な外科手術を行うことなく、移植組成物
の生体親和性を簡単に利用することができる。
領域内の生来の組織の再成長を誘発する能力である。治
癒すべき組織欠陥または負傷の在る場所に有効量の流動
化粘膜下組織組成物を注射することにより、大きな侵襲
的手術を行うことなく、この驚くべき特性を簡単に利用
できる。
が、下記の請求の範囲に記載され定義された発明の範囲
および精神の範囲で種々の変化および変更が存在する。
Claims (32)
- 【請求項1】組織移植組成物を調製する方法であって、
腸粘膜下組織を含む腸組織を粉砕する工程と、得られた
粉砕腸組織を水和して25℃で約2cps〜約300,000cpsの粘
度を有する流体として前記組織移植構造体を提供する工
程とを含む方法。 - 【請求項2】粉砕工程が、腸組織を冷凍し、冷凍した腸
粘膜下組織を磨砕する工程を含む請求項1に記載の方
法。 - 【請求項3】粉砕工程が、腸組織を凍結乾燥し、凍結乾
燥した腸組織を磨砕する工程を含む請求項1に記載の方
法。 - 【請求項4】粉砕工程が、腸組織を高剪断混合器内で処
理する工程を含む請求項1に記載の方法。 - 【請求項5】組織移植組成物を殺菌する工程を更に含む
請求項1に記載の方法。 - 【請求項6】腸組織が粘膜下組織と粘膜基底部とを含ん
でおり、前記粘膜下組織と粘膜基底部は、温血脊椎動物
の腸粘膜の筋層および管腔部から分層されるものである
請求項1に記載の方法。 - 【請求項7】腸組織が本質的に脊椎動物の腸断片の粘膜
下組織、粘膜筋層および細胞層からなるものである請求
項6に記載の方法。 - 【請求項8】粉砕した腸組織を、組織を可溶化して組織
移植組成物を実質的に均質な溶液として提供するのに十
分な時間、プロテアーゼを用いて分解する工程を更に含
む請求項1に記載の方法。 - 【請求項9】実質的に均質な溶液を中和してプロテアー
ゼを不活化する工程を更に含む請求項8に記載の方法。 - 【請求項10】腸組織が粘膜下組織と粘膜基底部とを含
んでおり、前記粘膜下組織と粘膜基底部は、温血脊椎動
物の腸粘膜の筋層および管腔部から分層されるものであ
る請求項8に記載の方法。 - 【請求項11】腸組織が本質的に脊椎動物の腸断片の粘
膜下組織、粘膜筋層および細胞層からなるものである請
求項10に記載の方法。 - 【請求項12】実質的に均質な溶液から可溶化した組織
を分離する工程を更に含む請求項10に記載の方法。 - 【請求項13】組織移植組成物を調製する方法であっ
て、腸粘膜下組織を、この粘膜下組織を可溶化して実質
的に均質な溶液を形成するのに十分な時間、水溶液中に
おいてプロテアーゼを用いて分解する工程を含む方法。 - 【請求項14】実質的に均質な溶液を中和してプロテア
ーゼを不活化する工程を更に含む請求項13に記載の方
法。 - 【請求項15】実質的に均質な溶液から可溶化した組織
を分離する工程を更に含む請求項13に記載の方法。 - 【請求項16】腸組織が粘膜下組織と粘膜基底部とを含
んでおり、前記粘膜下組織と粘膜基底部は、脊椎動物の
腸粘膜の筋層および管腔部から分層されるものである請
求項13に記載の方法。 - 【請求項17】腸組織が本質的に脊椎動物の腸断片の粘
膜下組織、粘膜筋層および細胞層からなるものである請
求項16に記載の方法。 - 【請求項18】流動化された腸粘膜下組織を含む粉砕し
た腸組織を水溶性の媒体に懸濁した懸濁液を含む組織組
成物。 - 【請求項19】25℃で約2cps〜約300,000cpsの粘度を有
する請求項18に記載の組成物。 - 【請求項20】腸組織が温血脊椎動物の小腸断片の粘膜
下組織と粘膜基底部とを含んでおり、前記粘膜下組織と
粘膜基底部は、小腸の前記断片の粘膜の筋層および管腔
部から分層されるものである請求項18に記載の組成物。 - 【請求項21】腸組織が本質的に脊椎動物の腸断片の粘
膜下組織、粘膜筋層および細胞層からなるものである請
求項20に記載の組成物。 - 【請求項22】流動化された腸粘膜下組織を含む、プロ
テアーゼ分解した腸組織を水溶性キャリア中に含有する
組成物。 - 【請求項23】25℃で約2cps〜約300,000cpsの粘度を有
する請求項22に記載の組成物。 - 【請求項24】腸組織が温血脊椎動物の小腸断片の粘膜
下組織と粘膜基底部とを含んでおり、前記粘膜下組織と
粘膜基底部は、小腸の前記断片の粘膜の筋層および管腔
部から分層されるものである請求項22に記載の組成物。 - 【請求項25】腸組織が本質的に脊椎動物の腸断片の粘
膜下組織、粘膜筋層および細胞層からなるものである請
求項24に記載の組成物。 - 【請求項26】プロテアーゼを実質的に含有しない請求
項22に記載の組成物。 - 【請求項27】密閉された小袋の形態に作成され、 粉砕された流動化された腸組織またはプロテアーゼ分解
され流動化された腸組織の懸濁液を含む流動化された組
織移植組成物を含有する組織移植構成体であって、 前記腸組織が粘膜下組織と粘膜基底部とを含んでおり、
この粘膜下組織と粘膜基底部は、温血脊椎動物の腸粘膜
の筋層および管腔部から分層されるものである組織移植
構成体。 - 【請求項28】腸組織が本質的に脊椎動物の腸断片の粘
膜下組織、粘膜筋層および細胞層からなるものである請
求項27に記載の組織移植構成体。 - 【請求項29】粉末形態である、乾燥腸粘膜下組織。
- 【請求項30】粉末形態である、乾燥プロテアーゼ可溶
化腸粘膜下組織。 - 【請求項31】流動化された腸粘膜下組織を含む粉砕し
た腸組織を水溶性の媒体に懸濁した懸濁液を含み、投与
するための注射用具入った、注射可能な組織組成物。 - 【請求項32】流動化された腸粘膜下組織を含む、プロ
テアーゼ分解した腸組織を水溶性キャリア中に含有し、
投与するための注射用具に入った、注射可能な組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/976,156 | 1992-11-13 | ||
US07/976,156 US5275826A (en) | 1992-11-13 | 1992-11-13 | Fluidized intestinal submucosa and its use as an injectable tissue graft |
PCT/US1993/010861 WO1994011008A1 (en) | 1992-11-13 | 1993-11-10 | Fluidized intestinal submucosa and its use as an injectable tissue graft |
Publications (2)
Publication Number | Publication Date |
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JPH08506799A JPH08506799A (ja) | 1996-07-23 |
JP3534408B2 true JP3534408B2 (ja) | 2004-06-07 |
Family
ID=25523793
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JP51232594A Expired - Lifetime JP3534408B2 (ja) | 1992-11-13 | 1993-11-10 | 流動化腸粘膜下組織および注射可能な組織移植体としてのその使用 |
Country Status (22)
Country | Link |
---|---|
US (2) | US5275826A (ja) |
EP (1) | EP0671922B1 (ja) |
JP (1) | JP3534408B2 (ja) |
AT (1) | ATE192654T1 (ja) |
AU (1) | AU677974B2 (ja) |
BR (1) | BR9307419A (ja) |
CA (1) | CA2149324C (ja) |
CZ (1) | CZ124095A3 (ja) |
DE (1) | DE69328625T2 (ja) |
DK (1) | DK0671922T3 (ja) |
ES (1) | ES2148309T3 (ja) |
FI (1) | FI952337A (ja) |
GR (1) | GR3034144T3 (ja) |
HU (1) | HU218891B (ja) |
MX (1) | MX9307046A (ja) |
NO (1) | NO951881L (ja) |
NZ (2) | NZ258032A (ja) |
PL (1) | PL174426B1 (ja) |
PT (1) | PT671922E (ja) |
RU (1) | RU2148379C1 (ja) |
SK (1) | SK282122B6 (ja) |
WO (1) | WO1994011008A1 (ja) |
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DE69328625D1 (de) | 2000-06-15 |
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HUT73965A (en) | 1996-10-28 |
RU2148379C1 (ru) | 2000-05-10 |
HU9501403D0 (en) | 1995-06-28 |
US5275826A (en) | 1994-01-04 |
FI952337A0 (fi) | 1995-05-12 |
AU5552394A (en) | 1994-06-08 |
HU218891B (hu) | 2000-12-28 |
ATE192654T1 (de) | 2000-05-15 |
NO951881L (no) | 1995-05-12 |
EP0671922B1 (en) | 2000-05-10 |
PL174426B1 (pl) | 1998-07-31 |
PL309000A1 (en) | 1995-09-18 |
NZ299279A (en) | 2000-08-25 |
SK282122B6 (sk) | 2001-11-06 |
WO1994011008A1 (en) | 1994-05-26 |
EP0671922A4 (en) | 1996-08-21 |
PT671922E (pt) | 2000-08-31 |
GR3034144T3 (en) | 2000-11-30 |
AU677974B2 (en) | 1997-05-15 |
BR9307419A (pt) | 1999-08-31 |
MX9307046A (es) | 1995-01-31 |
CA2149324A1 (en) | 1994-05-26 |
DE69328625T2 (de) | 2001-02-08 |
FI952337A (fi) | 1995-05-12 |
US5516533A (en) | 1996-05-14 |
EP0671922A1 (en) | 1995-09-20 |
DK0671922T3 (da) | 2000-08-28 |
JPH08506799A (ja) | 1996-07-23 |
CZ124095A3 (en) | 1995-11-15 |
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