JP5462175B2 - 脊髄組織を治療する装置および方法 - Google Patents

脊髄組織を治療する装置および方法 Download PDF

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JP5462175B2
JP5462175B2 JP2010529042A JP2010529042A JP5462175B2 JP 5462175 B2 JP5462175 B2 JP 5462175B2 JP 2010529042 A JP2010529042 A JP 2010529042A JP 2010529042 A JP2010529042 A JP 2010529042A JP 5462175 B2 JP5462175 B2 JP 5462175B2
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wound
vacuum
spinal cord
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JP2011500163A5 (ja
JP2011500163A (ja
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アージェンタ、ルイス、シー.
キャロル、デービット、エル.
リーバイ、ニコール、エイチ.
リウ、ジエ
モリクワス、マイケル、ジェイ.
タッター、スティーブン
ワグナー、ウィリアム、ディー.
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Wake Forest University Health Sciences
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/90Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing
    • A61M1/91Suction aspects of the dressing
    • A61M1/916Suction aspects of the dressing specially adapted for deep wounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61F13/01021
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/71Suction drainage systems
    • A61M1/74Suction control
    • A61M1/75Intermittent or pulsating suction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/90Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing
    • A61M1/91Suction aspects of the dressing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
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    • A61M1/90Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing
    • A61M1/96Suction control thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00Anatomical parts of the body
    • A61M2210/10Trunk
    • A61M2210/1003Spinal column

Description

本発明は、全体として、損傷または機能低下した脊髄組織を準大気圧を使って治療する装置および方法に関し、より具体的には(これに限定されるものではないが)、回復可能または回復不可能な損傷を受けた脊髄組織を治療する装置および方法に関する。
損傷または機能低下した脊髄組織の治療において、脊髄に係わる生体構造、生理機能、および病理学的過程には特別な関心が寄せられる。3次元生体構造と、神経細胞(他の神経細胞および他の支持細胞との特定の空間関係に、機能が依存する)の微細構造関係との双方を維持し、神経細胞の存続に必要である適切に酸素を含んだ血流および均一な基質を保つことは、脊髄組織の生存および機能に必要不可欠である。さらに、脊髄細胞が再生不可能な場合には、神経細胞の生存率を可能な限り最大限に伸ばす必要性が重視される。これらの理由等から、脊髄における開放空間および閉鎖空間双方の病変治療が特に注目される。
脊髄組織の生存を脅かす臨床問題において、脊髄の浮腫、感染、および血液供給を管理することは非常に重要である。脊髄は、外傷および損傷への反応として、著しい量の間質浮腫を生じる。脊髄は閉鎖空間(硬膜および脊柱管)に閉じ込められているため、浮腫は脊髄内部で周囲を圧迫し、脊髄の血流および栄養供給の機能を低下させて脊髄の生理学的回復を著しく損ない、結果的に脊髄の機能低下および細胞死を進行させることが多い。現在、浮腫を軽減する治療薬としては、グルココルチコイド(デキサメタゾン、プレドニゾン、メチルプレドニゾン)、利尿薬などの薬剤が利用でき、多様な外科的減圧術も行われている。しかし、これらを利用した療法では結果が不規則で予測できず、薬剤による合併症、感染、および手術による合併症などの欠点もある。
また、脊髄内の感染および浮腫は、致命的な結果を招き、急速に広がる可能性が高いため、迅速かつ効果的な治療が必要不可欠である。髄腔内空間、脊髄柔組織、およびその周辺構造に影響を及ぼす病変の治療に利用できる適切な方法は、現在ほとんどない。身体の他部分の組織はドレッシング材の交換で治療できるが、脊髄は、構造が不安定で、感染が広がる傾向があり、損傷が進行するおそれがあるため、このタイプの治療に適していない。脊髄損傷および他の病変による炎症および免疫反応は、初期の損傷と等しいかそれ以上の長期的影響があるという証拠もある。浮腫に続き二次的に起こる血流減少に対する脊髄の反応は、低酸素および虚血・再潅流傷害につながる。これらの損傷は、神経病理学的続発症の一因となり、ひいては脊髄損傷の有害な転帰を著しく助長する。
また脊髄は、機能し、生存するため、酸素を含んだ血液の供給を絶えず必要とする。血流が完全に中断されると、脊髄は、数分以内に不可逆的損傷を受ける。ただし、脊髄は、それより長時間生存能力を維持し、血流の減少から回復することもできる。虚血および比較的無機能の状態が数日続いた脊髄病巣でも、回復できるという証拠がある。この発見により、不可逆的損傷領域を取り囲むペナンブラまたは虚血周辺領域と呼ばれる虚血領域の概念が生まれた。虚血領域における二次的現象は、損傷した神経細胞による興奮性毒の局所的な放出、病巣の血流の変化、および浮腫である。
脊椎の血管病変の原因として考えられるのは、灌流圧低下による脊髄細胞への血流不足、血管が破裂した結果または隣接する組織の圧縮により脊髄の局所的領域に直接生じる損傷、粥状動脈硬化症、動脈瘤、炎症といった脊髄血管の内因性疾患、あるいは心臓など他所からの遠隔血栓が脊髄血管を閉塞した場合などである。
髄腔内出血の場合、通常、出血は小規模で始まり、圧力解離により体積を増して、隣接する脊髄組織の変位および圧縮に至る。出血周囲に隣接した被圧縮組織内の浮腫は、脊髄組織のより広い領域の機能を低下させて病態の規模を拡大し、悪化させる。隣接した脊髄内の浮腫は、通常12〜72時間にわたり徐々に悪化を生じるおそれがある。髄腔内出血の翌週に浮腫が発生すると、特に高齢者の場合、予後が悪化することが多い。血腫周囲の組織は変位し、圧縮されるが、必ずしも致命的に機能が低下するわけではない。血腫が再吸収され、隣接する浮腫が縮小し、病変組織が機能を回復するに伴い、改善が見られることもある。
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【特許文献117】 米国特許第4184510号明細書
【特許文献118】 米国特許第4465485号明細書
【特許文献119】 米国特許第4664662号明細書
【特許文献120】 米国特許第4710165号明細書
【特許文献121】 米国特許第4256109号明細書
【特許文献122】 米国特許第2122121号明細書
【特許文献123】 米国特許第5330452号明細書
【特許文献124】 米国特許第5344415号明細書
【特許文献125】 米国特許第5437651号明細書
【特許文献126】 米国特許第5496262号明細書
【特許文献127】 米国特許第5588955号明細書
【特許文献128】 米国特許第5717030号明細書
【特許文献129】 米国特許第5733884号明細書
【特許文献130】 米国特許第6187047号明細書
【特許文献131】 米国特許出願公開第2001/0043943号明細書
【特許文献132】 米国特許出願公開第2005/0101940号明細書
【特許文献133】 米国特許出願公開第2005/0124966号明細書
【特許文献134】 米国特許出願公開第2005/0148913号明細書
【特許文献135】 米国特許出願公開第2005/0197645号明細書
【特許文献136】 米国特許出願公開第2005/0203452号明細書
【特許文献137】 米国特許出願公開第2005/0209574号明細書
【特許文献138】 米国特許出願公開第2005/0222527号明細書
【特許文献139】 米国特許出願公開第2005/0222528号明細書
【特許文献140】 米国特許出願公開第2005/0222544号明細書
【特許文献141】 米国特許出願公開第2005/0228329号明細書
【特許文献142】 米国特許出願公開第2005/0261615号明細書
【特許文献143】 米国特許出願公開第2005/0261642号明細書
【特許文献144】 米国特許出願公開第2006/0025727号明細書
【特許文献145】 米国特許出願公開第2006/0100586号明細書
【特許文献146】 米国特許出願公開第2007/0260226号明細書
【特許文献147】 米国特許第4156066号明細書
【特許文献148】 米国特許第1963258号明細書
【特許文献149】 米国特許第847475号明細書
【特許文献150】 米国特許第114754号明細書
【特許文献151】 米国特許第1416108号明細書
【特許文献152】 米国特許第5192282号明細書
【特許文献153】 米国特許第5968047号明細書
【特許文献154】 米国特許第6887246号明細書
【特許文献155】 米国特許出願公開第2006/0213527号明細書
【特許文献156】 米国特許出願公開第2004/0225178号明細書
【特許文献157】 米国特許第4221215号明細書
【特許文献158】 米国特許第5484399号明細書
【特許文献159】 米国特許第3429313号明細書
【特許文献160】 米国特許第7279612号明細書
【特許文献161】 米国特許出願公開第2007/0071790号明細書
【特許文献162】 米国特許出願公開第2003/0108587号明細書
【特許文献163】 米国特許第5951295号明細書
【特許文献164】 米国特許第7175625号明細書
【特許文献165】 米国特許出願公開第2006/0029650号明細書
【特許文献166】 米国特許第5717005号明細書
【特許文献167】 米国特許第4753232号明細書
【特許文献168】 米国特許第4499896号明細書
【特許文献169】 米国特許第6325788号明細書
【特許文献170】 米国特許第3782387号明細書
【特許文献171】 米国特許第6793633号明細書
【特許文献172】 米国特許第5224947号明細書
【特許文献173】 米国特許第5456267号明細書
【特許文献174】 米国特許第5743912号明細書
【特許文献175】 米国特許第7128735号明細書
【特許文献176】 米国特許第6485503号明細書
【特許文献177】 米国特許第5447492号明細書
【特許文献178】 米国特許出願公開第2007/0032754号明細書
【特許文献179】 米国特許出願公開第2007/0219585号明細書
【特許文献180】 米国特許出願公開第2003/0187367号明細書
【特許文献181】 米国特許出願公開第2008/0208171号明細書
【特許文献182】 米国特許第4187852号明細書
【特許文献183】 米国特許第5736372号明細書
【特許文献184】 米国特許第5766618号明細書
【特許文献185】 米国特許第7722894号明細書
【特許文献186】 米国特許出願公開第2003/0118692号明細書
【特許文献187】 米国特許出願公開第2005/0063939号明細書
【特許文献188】 米国特許出願公開第2006/0263417号明細書
【特許文献189】 米国特許出願公開第2007/0208420号明細書
【特許文献190】 米国特許出願公開第2008/0112998号明細書
【特許文献191】 米国特許出願公開第2009/0093565号明細書
【特許文献192】 米国特許出願公開第2009/0148945号明細書
【特許文献193】 米国特許出願公開第2009/0325859号明細書
【特許文献194】 米国特許第7066960号明細書
【特許文献195】 米国特許第6641604号明細書
【特許文献196】 米国特許第7931651号明細書
【特許文献197】 米国特許出願公開第2008/0208147号明細書
【特許文献198】 米国特許出願公開第2009/0254120号明細書
【特許文献199】 米国特許出願公開第2010/0121229号明細書
【特許文献200】 デンマーク特許第064,055号明細書
【特許文献201】 欧州特許第0117632号明細書
【特許文献202】 欧州特許第0424165号明細書
【特許文献203】 欧州特許出願公開第0485657号明細書
【特許文献204】 仏国特許第1303238号明細書
【特許文献205】 仏国特許第0500253号明細書
【特許文献206】 英国特許第1549756号明細書
【特許文献207】 英国特許出願公開第190203090号明細書
【特許文献208】 スウェーデン特許第84485号明細書
【特許文献209】 ソビエト連邦特許第1268175号明細書
【特許文献210】 国際公開第89/04158号
【特許文献211】 国際公開第01/89431号
【特許文献212】 国際公開第02/043634号
【特許文献210】 国際公開第03/101608号
【特許文献211】 独国特許発明第1963258号明細書
【特許文献212】 独国特許発明第847475号明細書
【特許文献213】 英国特許第114754号明細書
【特許文献214】 ソビエト連邦特許第1416108号明細書
【特許文献215】 国際公開第2008/063281号
【特許文献216】 独国特許発明第29504378号明細書
【特許文献217】 欧州特許第0880953号明細書
【特許文献218】 国際公開第00/07653号
【特許文献219】 国際公開第00/15277号
【特許文献220】 国際公開第00/26100号
【特許文献221】 国際公開第00/30567号
【特許文献222】 国際公開第00/32247号
【特許文献223】 国際公開第00/38552号
【特許文献224】 国際公開第00/42958号
【特許文献225】 国際公開第01/37922号
【特許文献226】 国際公開第01/49233号
【特許文献227】 国際公開第03/005943号
【特許文献228】 国際公開第03/101385号
【特許文献229】 国際公開第05/102234号
【特許文献224】 国際公開第93/09727号
【特許文献225】 国際公開第94/20041号
【特許文献226】 国際公開第96/15745号
【特許文献227】 欧州特許第0777504号明細書
【特許文献228】 欧州特許第0853950号明細書
【特許文献229】 欧州特許第1088569号明細書
【特許文献230】 英国特許第2329127号明細書
【特許文献231】 英国特許第2333965号明細書
【特許文献232】 英国特許第2336546号明細書
【特許文献233】 英国特許第2342584号明細書
【特許文献234】 英国特許第2344531号明細書
【特許文献235】 英国特許第114754号明細書
【特許文献236】 英国特許第2351025号明細書
【特許文献237】 国際公開第00/21586号
【特許文献238】 国際公開第00/38755号
【特許文献239】 国際公開第00/59418号
【特許文献240】 国際公開第00/59424号
【特許文献241】 国際公開第00/61206号
【特許文献242】 国際公開第00/64394号
【特許文献243】 国際公開第01/34223号
【特許文献244】 国際公開第01/85248号
【特許文献245】 国際公開第96/05873号
【特許文献246】 国際公開第99/13793号
【特許文献239】 国際公開第91/00718号
【特許文献240】 国際公開第92/20299号
【特許文献241】 英国特許第641061号明細書
【特許文献242】 英国特許第1273342号明細書
【特許文献243】 独国特許発明第2809828号明細書
【特許文献244】 国際公開第91/16030号
【特許文献245】 独国特許発明第561757号明細書
【特許文献246】 国際公開第90/11795号
【特許文献247】 国際公開第92/19313号
【特許文献248】 独国特許発明第4111122号明細書
【特許文献249】 独国特許発明第847475号明細書
【特許文献250】 英国特許第2195255号明細書
【特許文献251】 欧州特許第0620720号明細書
【特許文献252】 欧州特許第0688189号明細書
【特許文献253】 国際公開第80/01139号
【特許文献254】 国際公開第87/00439号
【特許文献255】 欧州特許第1457164号明細書
【非特許文献】
【0007】
【非特許文献1】 PARIKH, R.S., et al., "Self−adhesive drape (Opsite) for management of leaking abdominal wounds", Indian J. Gastroenterol., 19(4):178−180 (October / December 2000). NPL−631
【非特許文献2】 ALEXIS, A.F., et al., "Reassessment of the suction blister model of wound healing: introduction of a new higher pressure device", Int. J. Dermatol., 38(8):613−617 (August 1999). NPL−632
【非特許文献3】 GNANARAJ, J., "A simple, sterile, low−cost, closed suction drainage system", Trop. Doct., 27(2):104 (April 1997). NPL−633
【非特許文献4】 KLEMM, K.W., "Antibiotic bead chains", Clin. Orthop. Rel. Res., (295):63−76 (October 1993). NPL−634
【非特許文献5】 PIGNATTI, M., et al., "Mobile−VAC for the treatment of lower limb ulcers", Plast. Reconstr. Surg., 108(6)1837−1838 (November 2001). NPL−635
【非特許文献6】 SCHAUM, KD., "Payment strategies: a new medicare part B wound care policy", Adv. Skin & Wound Care, 14 (5):238−240 (September / October 2001). NPL−636
【非特許文献7】 CHARIKER, M.E., Presentation entitled, "Vacuum therapy in wound management", (Chariker deposition exhibit no. 1220), dated October 27, 2005. NPL−637
【非特許文献8】 CHARIKER, M.E., Presentation entitled, "Closed wound suction", (Chariker deposition exhibit no. 1219), dated March 17, 2005. NPL−638
【非特許文献9】 DAVYDOV, Y.A., et al., "The bacteriological and cytological assessment of vacuum therapy of purulent wounds", Vestnik Khirurgii imeni I.I. Grekova, (1 sheet of title page and pp. 48−52, 5 sheets of Russian text and English abstract on page 52); 141(10):48−52, (October 1988). DV3
【非特許文献10】 DAVYDOV, Y.A., et al., "Bacteriological and cytological assessment of vacuum therapy of purulent wounds," (7 sheets of translation, pp. 48−52 of Russian text and English abstract on page 52); 141(10):48−52 (October 1988). DV4
【非特許文献11】 DAVYDOV, Y.A., et al., "Vacuum therapy in the treatment of purulent lactation mastitis", Vestnik Khirurgii lmeni I.I. Grekova, ( 1 Sheet of Title page and pp. 66−70, 6 sheets of Russian text and English abstract on page 70); 137 (11):66−70, (November 1986). DV6
【非特許文献12】 DAVYDOV, Y.A., et al., "Vacuum therapy in treatment of acute purulent diseases of soft tissues and purulent wounds," Vestnik Khirurgii (Surgeons Herald), No. 9 Medicine Publishers, (5 sheets of translation), (1986). DV11
【非特許文献13】 ARGENTA, L.C., et al., "Vacuum−assisted closure: state of clinic art", Plast. Reconstr. Surg., 117 (7 Suppl.): 127S−142S (June 2006). WFU−64
【非特許文献14】 CHUNG, C.J., et al., "Case review: management of life−threatening sepsis and wound healing in a Klippel−Trenaunay patient using serial surgical debridements and vacuum−assisted closure", Eur. J. Plast. Surg., 26:214−216 (2003). WFU−61
【非特許文献15】 DEDMOND, B.T., et al., "Subatmospheric pressure dressings in the temporary treatment of soft tissue injuries associated with type III open tibial shaft fractures in children", J. Pediatr. Orthop., 26(6):728−732, (November − December 2006). WFU−67
【非特許文献16】 DEDMOND, B.T., et al., "The use of negative−pressure wound therapy (NPWT) in the temporary treatment of soft tissue injuries associated with high−energy open tibial shaft fractures", J. Orthop. Trauma, 21(1):11−17, (January 2007). WFU−68
【非特許文献17】 GEMEINHARDT, K.D., et al., "Vacuum−assisted closure for management of a traumatic neck wound in a horse", Equine Veterinary Education, 17(1):27−33, (2005). WFU−72
【非特許文献18】 LAVERTY, D., et al., "Negative pressure wound therapy in the management of orthopedic wounds", Ostomy Wound Manage., 50(11A suppl):18S−9S (November 2004). WFU−56
【非特許文献19】 MOLNAR, J.A., "Applications of negative pressure wound therapy to thermal injury", Ostomy Wound Manage., 50(4A suppl):17−9 (April 2004). WFU−58
【非特許文献20】 MOLNAR, J.A., "The science behind negative pressure wound therapy", Ostomy Wound Manage., 50 (4A suppl):2−5 (April 2004). WFU−59
【非特許文献21】 MOLNAR, J.A., et al., "Management of an acute thermal injury with subatmospheric pressure", J. Burns Wounds, 4:83−92, 4:e5 (published online March 24, 2005). WFU−43
【非特許文献22】 MORYKWAS, M.J., et al., "Effects of varying levels of subatmospheric pressure on the rate of granulation tissue formation in experimental wounds in swine", Ann. Plast. Surg., 47(5):547−551 (November 2001). WFU−44
【非特許文献23】 PLIKAITIS, C.M., et al., "Subatmospheric pressure wound therapy and the vacuum−assisted closure device: basic science and current clinical successes", Expert Rev. Med. Devices, 3(2):175−184, (March 2006). WFU−63
【非特許文献24】 SCHLATTERER, D., et al., "Orthopedic indications for negative pressure wound therapy", Ostomy Wound Manage., 51 (2A suppl):27S−8S (February 2005). WFU−57
【非特許文献25】 SCHNEIDER, A.M., et al., "Re: use of specialized bone screws for intermaxillary fixation: reply", Ann. Plast. Surg., 47 (1): 93, (July 2001). WFU−70
【非特許文献26】 WEBB, L.X., et al., "The contaminated high−energy open−fracture: a protocol to prevent and treat inflammatory mediator storm−induced soft−tissue compartment syndrome (IMSICS)", J. Am. Acad. Orthop. Surg., 14(10):SA82−S86 (October 2006). WFU−69
【非特許文献27】 YANG, C.C., et al., "Vacuum−assisted closure for fasciotomy wounds following compartment syndrome of the leg", J. Surg. Orthop. Adv., 15(1):19−23 (Spring 2006). WFU−66
【非特許文献28】 ARGENTA, A., et al., "Deformation of superficial and deep abdominal tissues with application of a controlled vacuum", European Tissue Repair Society, Focus group meeting Topical Negative Pressure (TNP) Therapy, London UK ( 4−6 December 2003). WFU−55
【非特許文献29】 ARGENTA, L.C., et al., "The V.A.C. as an adjunct for treatment for abdominal wounds", 66th Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, San Francisco, CA, pp. 330−331; 1 sheet of abstract (September 21−24 1997). WFU−39
【非特許文献30】 ARGENTA, L.C., et al., "Vacuum assisted closure of chronic wounds", 65th Annual Scientific Meeting, American Society of Plastic and Reconstructive Surgeons, Dallas, TX, pp. 226−227; 1 sheet of abstract (November 9−13, 1996). WFU−37
【非特許文献31】 DEFRANZO, A.J., et al., "The use of V.A.C. therapy for treatment of lower extremity wounds with exposed bone", 68th Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, New Orleans, LA, pp. 37−38; 2 sheets of abstract (October 24−27, 1999). WFU−42
【非特許文献32】 KORTESIS, B., et al., "Vacuum−assisted closure for the treatment of open tibia fractures", 72nd Annual Meeting of the
American Society of Plastic Surgeons, San Diego, CA, pp. 172−3; 1 sheet of abstract (October 25−29, 2003). WFU−41
【非特許文献33】 KREMERS, L., et al., "Effect of topical sub−atmospheric pressure treatment on angiotensin I and II levels post burn", 35th Annual Meeting, Abstract printed in J. Burn Care Rehabilitation, page S44, Abstract no. 3 American Burn Association, Miami, Florida (April 1−4 2003). WFU−54
【非特許文献34】 MOLNAR, J.A., et al., "Improved skin graft adherence and vascularization of integra(R) using subatmospheric pressure - a laboratory study", Abstract printed in Burn Care & Rehabilitation, page S111, Abstract no. 141; American Bum Meeting, 34th Annual Meeting, Chicago, IL, (April 24−27 2002). WFU−51
【非特許文献35】 MORYKWAS, M.J., et al., "Negative pressure treatment of burned extremities", 65th Annual Scientific Meeting, American Society of Plastic and Reconstructive Surgeons, Dallas, TX, pp. 86−87; 1 sheet of abstract (November 9−13, 1996). WFU−36
【非特許文献36】 MORYKWAS, M.J., et al., "The effect of V.A.C.(TM) therapy on the length of stay, total charges and average daily charge for patients assigned to DRG 263: analysis of 13 consecutive quarters", presented in part at the 28th Annual Conference of the Wound, Ostomy, and Continence Nurses Society, Seattle, WA, (15 sheets) (June 15−19, 1996). WFU−52
【非特許文献37】 PARK, C.A., et al., "Outpatient use of Integra(r) and subatmospheric pressure in the management of wound and burn reconstruction", J. Burn Care Rehabil., 26(2 suppl.):S113, Chicago, IL, (May 10−13, 2005). WFU−62
【非特許文献38】 SCHNEIDER, A.M., et al., "Muscle flap survival after complete venous occlusion by application of a negative pressure device", 66th Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, San Francisco, CA, pp. 300−302; 2 sheets of abstract (September 21−24 1997). WFU−38
【非特許文献39】 SCHNEIDER, A.M., et al., "Treatment of brown recluse spider bite wounds by external application of sub−atmospheric pressure", 68th Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, New Orleans, LA, page 35; 1 sheet of abstract (October 24−27, 1999). WFU−40
【非特許文献40】 WEBB, L.X., "Use of negative pressure devices in highly contaminated, high energy wounds", Extremity War Injuries: State of the Art and Future Directions, AAOS/OTA Extremity War Injures Symposium, January 24−27, 2006, [Abstract]. WFU−65
【非特許文献41】 MORYKWAS, M.J., "Basic Research and Animal Studies," Presentation at the European Topical Negative Pressure Meeting in Salsbury, England, (June 2005). WFU−71
【非特許文献42】 DEFRANZO, A.J., et al., "Vacuum assisted closure of the abdominal wall", 73rd Annual Meeting, American Association of Plastic Surgeons, Philadelphia, PA (2004), 1 sheet of abstract. WFU−60
【非特許文献43】 ARGENTA, P.A., et al., "Vacuum−assisted closure in the treatment of complex gynecologic wound failures," Obstet. Gynecol., 99(3):497−501, (9 sheets) (March 2002). NPL−018
【非特許文献44】 AZAD, S., et al., "Topical negative pressure may help chronic wound healing," B.M.J., 324:1100 (1 sheet) (May 4, 2002). NPL−026
【非特許文献45】 BALLARD, K., et al., "Developments in wound care for difficult to manage wounds," Br. J. Nurs., 9(7):405−8,410,412 (April 13−26, 2000). NPL−030
【非特許文献46】 BALLARD, K., et al., "Vacuum−assisted closure," Nurs. Times, 97(35):51−2 (5 sheets) August 30 − September 5, 2001. NPL−031
【非特許文献47】 BALLARD, K., et al., "Use of vacuum−assisted closure therapy following foot amputation," Br. J. Nurs., 10(15 Supplement):S6, 8, 11−12 (August 2001). NPL−032
【非特許文献48】 BANWELL, P.E., "Topical negative pressure therapy in wound care," J. Wound Care, 8(2):79−84 (February 1999). NPL−034
【非特許文献49】 BARTELS, C.G., et al., "The vacuum sealing technique. A new approach to cover soft tissue defects, used after the resection of a leiomyosarcoma", (English abstract on 2nd page and 1 page printout from PubMed); Hautarzt, 52 (7):653−7 (July 2001). NPL−039
【非特許文献50】 BAUER, P., et al., "Possibilities of preliminary treatment of infected soft tissue defects by vacuum sealing and PVA foam", (English abstract on first page and 1 sheet PubMed abstract), Handchir. Mikrochir. Plast. Chir., 30(1):20−3 (January 1998). NPL−040
【非特許文献51】 BAYNHAM, S.A., et al., "Treating stage IV pressure ulcers with negative pressure therapy: a case report", Ostomy Wound Manage., 45(4):28−32, 34−35 (April 1999). NPL−041
【非特許文献52】 BRODY, G.S., "Biological creep", Plast. Reconstr. Surg., 92(6):1202−1203 (November 1993). NPL−060
【非特許文献53】 CAMPTON−JOHNSTON, S., et al., "Infected wound management: advanced technologies, moisture−retentive dressings, and die−hard methods", Crit. Care Nurs. Q, 24(2):64−77 (August 2001). NPL−068
【非特許文献54】 CHEN, K.D., et al., "Mechanotransduction in response to shear stress", J. Biol. Chem., 274(26):18393−18400, (June 25, 1999). NPL−081
【非特許文献55】 CLARE, M.P., et al., "Experience with the vacuum assisted closure negative pressure technique in the treatment of non−healing diabetic and dysvascular wounds", Foot Ankle Int., 23(10):896−901 (October 2002). NPL−084
【非特許文献56】 CLAXTON, M.J., et al., "Healing the diabetic wound and keeping it healed: modalities for the early 21st century", Curr. Diab. Rep., 2(6):510−8 (December 2002). NPL−086
【非特許文献57】 COGGRAVE, M., et al., "Topical negative pressure for pressure ulcer management", Br. J. Nurs., 11(6 Suppl):S29−31, S33−34, S36 (March 2002). NPL−089
【非特許文献58】 COLLIER, M., "Know how: Vacuum assisted closure (VAC)", Nurs. Times, 93(5):32−3 (January 29−February 4 1997). NPL−090
【非特許文献59】 COOPER, S.M., et al., "Topical negative pressure", Int. J. Dermatol., 39(12):896−8 (December 2000). NPL−098
【非特許文献60】 COZART, R.F., et al., "The use of controlled subatmospheric pressure to promote wound healing in preparation for split−thickness skin grafting in a fourth degree burn", Tenn. Med., 92(10):382−4 (October 1999). NPL−103
【非特許文献61】 CRO, C., et al., "Vacuum assisted closure system in the management of enterocutaneous fistulae," Postgrad. Med. J., 78(925):364−5 (November 2002). NPL−104
【非特許文献62】 DE FILIPPO, R.E., et al., "Stretch and growth: the molecular and physiologic influences of tissue expansion", Plast. Reconstr. Surg., 109(7):2450−2462 (June 2002). NPL−110
【非特許文献63】 DEVA, A.K., et al., "Vacuum−assisted closure of a sacral pressure sore", J. Wound Care, 6(7):311−312, (July 1997). NPL−114
【非特許文献64】 DUNFORD, C., "Hypergranulation tissue", J. Wound Care, 8(10):506−507 (November 1999). NPL−123
【非特許文献65】 DUNFORD, C.E., "Treatment of a wound infection in a patient with mantle cell lymphoma", Br. J. Nurs., 10(16):1058, 1060, 1062, 1064−5 (September 13−26, 2001). NPL−124
【非特許文献66】 ESPENSEN, E.H., et al., "Use of subatmospheric (VAC) therapy to improve bioengineered tissue grafting in diabetic foot wounds", J. Am. Podiatr. Med. Assoc., 92(7):395−7 (July − August 2002). NPL−142
【非特許文献67】 FLECK, T.M., et al., "The vacuum−assisted closure system for the treatment of deep sternal wound infections after cardiac surgery", Ann. Thorac. Surg., 74(5):1596−600 (November 2002). NPL−155
【非特許文献68】 FLEISCHMANN, W., et al., "Vacuum assisted closure of wounds following dermatofasciotomy of the leg", Unfallchirurg., (English abstract on page 284, and 1 sheet printout from PubMed); 99(4):283−7, (April 1996). NPL−161
【非特許文献69】 FORD, C.N., et al., "Interim analysis of a prospective, randomized trial of vacuum−assisted closure versus the healthpoint system in the management of pressure ulcers", Ann. Plast. Surg., (11 sheets); 49(1):55−61 (July 2002). NPL−163
【非特許文献70】 GOUTTEFANGEAS, C., et al., "Functional T lymphocytes infiltrate implanted polyvinyl alcohol foams during surgical wound closure therapy," Clin. Exp. Immunol., 124(3):398−405 (June 2001). NPL−173
【非特許文献71】 GREER, S.E., et al., "Subatmospheric pressure dressing for saphenous vein donor−site complications," Ann. Thorac. Surg., (6 sheets); 71(3):1038−40 (March 2001). NPL−176
【非特許文献72】 HAWKINS−BRADLEY, B., et al., "Treatment of a nonhealing wound with hypergranulation tissue and rolled edges", J. Wound Ostomy Continence Nurs., 29(6):320−324 (November 2002). NPL−187
【非特許文献73】 HARLAN, J.W., "Treatment of open sternal wounds with the vacuum−assisted closure system: a safe, reliable method", Plast. Reconstruct. Surg., 109(2):710−12 (February 2002). NPL−191
【非特許文献74】 HARTNETT, S., "Heparin−induced thrombocytopenia as the cause of gluteus muscle necrosis: a case study describing the benefits of multidisiplinary physical and psychosocial interventions", Ostomy Wound Manage., 47(5):18−26 (May 2001). NPL−194
【非特許文献75】 HERSH, R.E., et al., "A technique for the treatment of sternal infections using the vacuum assisted closure TM device", Heart Surg. Forum, 4(3):211−15 (2001). NPL−202
【非特許文献76】 INGBER, D.E., "Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology", Circ. Res., 91:877−887 (November 15, 2002). NPL−219
【非特許文献77】 KALAILIEFF, D., "Vacuum−assisted closure: wound care technology for the new millennium", Perspectives, 22(3):28−9 (Fall 1998). NPL−230
【非特許文献78】 KERCHER, K.W., et al., "Successful salvage of infected PTFE mesh after ventral hernia repair", Ostomy Wound Manage., 48(10):40−5 (October 2002). NPL−234
【非特許文献79】 KIERNAN, M., "The process of granulation and its role in wound healing", Community Nurse, 5(5):47−48 (June 1999). NPL−235
【非特許文献80】 KLOTH, L.C., "5 questions−and answers−about negative pressure wound therapy", Adv. Skin Wound Care, 15(5):226, 228−9 (September − October 2002). NPL−237
【非特許文献81】 KUSEL, C., "Use of V.A.C. (vacuum−assisted closure) therapy in general surgery: problem wounds deprived of air", Pflege Z., (and 1 sheet printout from PubMed); 55(6):408−412 (June 2002). NPL−245
【非特許文献82】 LABLER, L., et al., "Vacuum sealing of problem wounds", Swiss Surg., (English abstract on first page, 1 sheet printout from PubMed); 8(6):266−7 (2002). NPL−246
【非特許文献83】 MARSTON, W.A., et al., "The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial", Diabetes Care, 26(6) 10 pp., (Exhibit 271) (June 1, 2003). NPL−267
【非特許文献84】 MENDEZ−EASTMAN, S., "New treatment for an old problem: negative−pressure wound therapy", Nurs., 32(5):58−64. (12 sheets) (May 2002). NPL−279
【非特許文献85】 MULLER, G., "Vacuum dressing in septic wound treatment", Langenbecks Arch. Chir. Suppl. Kongressbd., (English abstract on page 537, and 1 sheet printout from PubMed); 114:537−41 (1997). NPL−301
【非特許文献86】 RAMNARINE, I.R., et al., "Vacuum−assisted closure in the paediatric patient with post−cardiotomy mediastinitis", Eur. J. Cardiothorac. Surg., 22:1029−31 (December 2002). NPL−342
【非特許文献87】 ROLLINS, H., "Hypergranulation tissue at gastrostomy sites", J. Wound Care, 9(3):127−129 (March 2000). NPL−346
【非特許文献88】 SCHAUM, K.D., "Medicare Part B negative pressure wound therapy pump policy. A partner for Medicare Part A PPS," Home Healthc. Nurse, 20(1):57−8 (January 2002). NPL−358
【非特許文献89】 SHAER, W.D., "Inexpensive vacuum−assisted closure employing a conventional disposable closed−suction drainage system", Plast. Reconstr. Surg., 107(1):292−3 (January 2001). NPL−365
【非特許文献90】 SAKLANI, A.P., et al., "Vacuum assisted closure system in the management of enterocutaneous fistula", Postgrad. Med. J., 78(925):699 (November 2002). NPL−370
【非特許文献91】 TAKEI, T., et al., "Molecular basis for tissue expansion: clinical implications for the surgeon", Plast. Reconstr. Surg., 102(1):247−258 (July 1998). NPL−395
【非特許文献92】 TANG, A.T.M., et al., "Vacuum−assisted closure to treat deep sternal wound infection following cardiac surgery", J. Wound Care, 9(5):229−30 (May 2000). NPL−397
【非特許文献93】 NIKKHAH, C., et al., "Re: use of specialized bone screws for intermaxillary fixation", Ann. Plast. Surg., 47(1): 93, (July 2001). NPL−413
【非特許文献94】 VOINCHET, V., et al., "Vacuum assisted closure. Wound healing by negative pressure", Ann. Chir. Plast. Esthet., (English abstract on first page, and 1 sheet printout from PubMed); 41(5):583−9, (October 1996). NPL−422
【非特許文献95】 VON GOSSLER, C.M., et al., "Rapid aggressive soft−tissue necrosis after beetle bite can be treated by radical necrectomy and vacuum suction−assisted closure", J. Cutan. Med. Surg., 4(4):219−222 (October 2000). NPL−424
【非特許文献96】 WILHELMI, B.J., et al., "Creep vs. stretch: a review of the viscoelastic properties of skin", Ann. Plast. Surg., 41 (2):215−219, (August 1998). NPL−436
【非特許文献97】 VVISEMAN, J., et al., "Aesthetic aspects of neurofibromatosis reconstruction with the vacuum−assisted closure system", Aesth. Plast. Surg., 25:326−31 (September − October 2001). NPL−440
【非特許文献98】 YOUNG, T., "Common problems in wound care: overgranulation", Br. J. Nursing, 4(3):169−170, (February 9−22, 1995). NPL−451
【非特許文献99】 ZIEGLER, U.E., et al., "Skin substitutes in chronic wounds", Zentralbl. Chir., (English abstract on first page; 1 sheet printout from PubMed); 126 Suppl 1:71−4 (2001). NPL−454
【非特許文献100】 STANNARD, J., "Complex orthopaedic wounds: prevention and treatment with negative pressure wound therapy", Orthop. Nurs., 23 Suppl 1:3−10 (10 sheets) (March − April 2004), presented at the 17th Annual Clinical Symposium on Advances in Skin & Wound Care, Dallas, TX (September 23, 2002). NPL−588
【非特許文献101】 PATEL, C.T.C., et al., "Vacuum−assisted wound closure: changing atmospheric pressure assists wound healing," AJN, 100:45−47 (2000). NPL−598
【非特許文献102】 MASTERS, J., "Reliable, inexpensive and simple suction dressings", Letters to the Editor, page 267, labeled 1998. NPL−602
【非特許文献103】 HAZELBAG, S., et al., "Cytokine profile of cervical cancer cells", Gynecol. Oncol., 83(2):235−243, (November 2001). NPL−613
【非特許文献104】 BEITZ, J.M., et al., "Abdominal wound with enterocutaneous fistula: a case study", J. Wound Ostomy Continence Nurs., 25(2):102−6, (March 1998). NPL−614
【非特許文献105】 BAXANDALL, T., "Healing cavity wounds with negative pressure", Elderly Care, 9(1):20, 22 (February − March 1997) NPL−615
【非特許文献106】 MCKINNEY, P.E., "Out−of−hospital and interhospital management of crotaline snakebite", Ann. Emerg. Med., 37 (2):168−174, (February 2001). NPL−616
【非特許文献107】 LEROY, S.C., et al., "Severe penile erosion after use of a vacuum suction device for management of erectile dysfunction in a spinal cord injured patient. Case report", Paraplegia, 32(2):120−123 (February 1994). NPL−617
【非特許文献108】 Slides and photographs of patient treatment, 19 sheets, (Exhibit D−152) (allegedly dated 1987). NPL−376
【非特許文献109】 Slides, drawings, photographs of patient treatment and presentation slides, 20 sheets, (Exhibit D−151) (allegedly dated 1987). NPL−377
【非特許文献1110】 Photographs of wound coverings and patient treatment, 16 sheets, (Exhibit D−240) (allegedly dated 1989). NPL−331
【非特許文献111】 Letter to Mr. Urs Tanner from Michael Baniak regarding: Updated Opinion of Non−infringement and Invalidity of Zamierowski U.S. Patent 4,969,880 and Argenta U.S. Patent 5,636,643, 30 pp., (Exhibit D−140) (dated August 23, 2004). NPL−255
【非特許文献112】 BANWELL, P.E., et al., "Topical negative pressure (TNP): the evolution of a novel wound therapy," J. Wound Care, 12 (1):22−8 (January 2003). NPL−035
【非特許文献113】 CARDOZO, M., "A case study of holistic wound management in intensive care", Br. J. Nurs., 12(11 Suppl):S35−37, S40−42 (June 2003). NPL−069
【非特許文献114】 COLLIER, M., "Topical negative pressure therapy", Nurs. Times, 99(5):54−5 (February 4−10, 2003). NPL−091
【非特許文献115】 DOMKOWSKI, P.W., et al., "Evaluation of vacuum−assisted closure in the treatment of poststerotomy mediastinitis," J. Thorac. Cardiovasc. Surg., 126(2):386−90 (August 2003). NPL−119
【非特許文献116】 EGINTON, M.T., et al., "A prospective randomized evaluation of negative−pressure wound dressings for diabetic foot wounds", Ann. Vasc. Surg., 17(6):645−9 (2003). NPL−132
【非特許文献117】 FERREIRA, M.C., et al., "The vacuum assisted closure of complex wounds: report of three cases", Rev. Hosp. Clin. Fac. Med. S. Paulo, 58(4):227−30 (2003). NPL−151
【非特許文献118】 FISHER, A., et al., "Vacuum assisted wound closure therapy", Issues Emerg. Health Technol., Issue 44, 6 pp. (March 2003). NPL−154
【非特許文献119】 HALLBERG, H., et al., "Vaginal construction with skin grafts and vacuum−assisted closure", Scand. J. Nast. Reconstr. Surg. Hand Surg., 37(2):97−101 (2003). NPL−184
【非特許文献120】 HESS, C.L? , et al., "A review of mechanical adjuncts in wound healing: hydrotherapy, ultrasound, negative pressure therapy, hyperbaric oxygen, and electrostimulation", Ann. Plast. Surg., 51(2):210−8 (August 2003). NPL−204
【非特許文献121】 HODZIC, J., et al., "Vacuum sealing of extensive wound healing disorders after kidney transplantation," Urologe A., (6 sheets in German, English abstract on page 2 and 1 sheet printout from PubMed); 42(8):1097−100 (August 2003) (Epub April 3, 2003). NPL−208
【非特許文献122】 KAUFMAN, M.W., et al., Vacuum−assisted closure therapy: wound care and nursing implications", Dermatol. Nurs., 15 (4):317−20, 323−236 (August 2003). NPL−232
【非特許文献123】 LUCKRAZ, H., et al− , Vacuum−assisted closure as a treatment modality for infections after cardiac surgery, J. Thorac. Cardiovasc. Surg., 125(2):301−5 (February 2003). NPL−260
【非特許文献124】 McGUINNESS, J.G., et al., "Vacuum−assisted closure of a complex pilonidal sinus", Dis. Colon Rectum, 46(2):274−6 (February 2003). NPL−272
【非特許文献125】 MORAN, S.G., et al., "Vacuum−assisted complex wound closure with elastic vessel loop augmentation: a novel technique", J. Wound Care, 12(6):212−3 (June 2003). NPL−298
【非特許文献126】 SCHIPPER, J., et al., "The preconditioning and prelamination of pedided and free microvascular anastomised flaps with the technique of vacuum assisted closure", Laryngorhinootologie, (English abstract on first page, and 2 sheets printout from PubMed); 82(6):421−7, (June 2003). NPL−364
【非特許文献127】 SHI, B., et al., "Effects of vacuum−assisted closure (VAC) on the expressions of MMP− 1, 2, 13 in human granulation wound", Zhonghua Zheng Xing Wai Ke Za Zhi, (English abstract on first page and 1 sheet printout from PubMed); 19 (4):279−81 (July 2003). NPL−366
【非特許文献128】 SILVER, F.H., et al., "Mechanobiology of force transduction in dermal tissue", Skin Res. Technol., 9(1):3−23 (February 2003). NPL−372
【非特許文献129】 SILVER, F.H , et al., "Mechanosensing and mechanochemical transduction: how is mechanical energy sensed and converted into chemical energy in an extracellular matrix?" Crit. Rev. Biomed. Eng., 31(4)255−331 (2003). NPL−373
【非特許文献130】 SKILLMAN, J., et al., "Vacuum assisted closure (VAC) dressing for skin graft application following exenteration of the orbit", Orbit, 22(1):63−5 (March 2003). NPL−375
【非特許文献131】 SONG, D.H., et al., "Vacuum assisted closure for the treatment of sternal wounds: the bridge between debridement and definitive closure", Plast. Recontr. Surg., 111(1):92−7 (January 2003). NPL−381
【非特許文献132】 WANNER, M.B., et al., "Vacuum−assisted wound closure for cheaper and more comfortable healing of pressure sores: a prospective study", Scand. J. Plast. Reconstruct. Surg. Hand Surg., 37(1):28−33 (2003). NPL−427
【非特許文献132】 WEAVER, B. "The nursing needs of a patient with a complicated abdominal wound", Prof. Nurse, 18(5):269−73 (January 2003). NPL−429
【非特許文献133】 WONGWORAWAT, M.D., et al., "Negative pressure dressings as an alternative technique for the treatment of infected wounds", Clin. Orthop. Relat. Res., (414):45−8 (September 2003). NPL−442
【非特許文献134】 JUCHLI, L., "Krankenpflege [Nursing] Practice and Theory of Promoting Health and Patient Care," Georg Thieme Verlag Stuttgart, labeled as "Anlage 6.1" 1991 (allegedly dated February 1991), and email dated May 30, 2007 labeled as "Anlage 6.2," both in German with English translations. DENA−WH1−005
【非特許文献135】 FLEISCHMANN, W., et al., "Combination osteosynthesis in the treatment of pylon fractures with soft tissue damage," labeled "Anlage NK10," pp. 178−181 and showing "6. German−Austrian−Swiss Trauma Conference in Vienna May 21−25, 1991," published in "Der Unfallchirurg" [The Traumatologist] in 1993, in German with English translation. DENA−WH1−006
【非特許文献136】 "Coldex," labeled as "Anlage NK12" in German with English translation. DENA−WH1−007
【非特許文献137】 TURNER, T.D., et al., eds., Excerpts from "Advances in wound management," including "Recent advances in wound management products" by T.D. Turner and "The role of foam dressings in wound management" by S. Thomas, Proceedings of a symposium held at the Welsh School of Pharmacy, University of Wales Institute of Science and Technology, Cardiff, 20−21 March 1985, labeled as "Anlage NK13," 1986. DENA−WH1−008
【非特許文献138】 FLEISCHMANN, W., et al., "Combination osteosynthesis in treating pilon fractures involving soft tissue injuries," in "Translation of an excerpt from the brochure regarding the Sixth German−Austrian−Swiss Accident Congress" allegedly dated 1991, in German with English translation. DENA−WH1−009
【非特許文献139】 ISO 10079−1, "International Standard," "Medical suction equipment - Part 1: electrically powered suction equipment - Safety requirements," dated May 15, 1991. DENA−WH2−005
【非特許文献140】 MOLNAR, J.A., "V.A.C. and burn care", presentation slides. WFU−74
【非特許文献141】 Slides regarding use of V.A.C. WFU−75
【非特許文献142】 Instruction Manual, Creative Medical Laboratories, Inc. P.O. Box 6347, Rochester, Minn. 55903. "TUGS" (Transportable Universal Gradient Suction).
【非特許文献143】 Deknatel, Div. of Howmedica, Inc. Quenns Village, NY 11429. "Pleur−evac. NPL−111
【非特許文献144】 Sparta Instrument Corp. 26602 Corporate Ave., Hayward, CA 94545. "Power Source Multi−Purpose Surgical Aspirator." NPL−383
【非特許文献145】 Wells Johnson Company, 2045 N. Forbes Blvd., Suite 106, Tucson, AZ. "Point 5 Aspirator." NPL−433
【非特許文献146】 Microtek Heritage, Inc. P.O. Box 2487, Columbus, MS 39704. "Wound−Evac ET." NPL−284
【非特許文献147】 Fleischmann, W. Wund Forum Spezial. IHW 94. "Vakuumversiegelung zurBehandlung von Probelmwunden" (with English translation: "Vacuum sealing for Treatment of Problematical Wounds." NPL−160
【非特許文献148】 Fleischmann, W. Acta Orthopaedica Belgica. Vol. 58, Suppl. 1−1992 "Treatmentof Bone and Soft Tissue Defects in Infected Nonunion." NPL−159
【非特許文献149】 Fleischmann, W. Strecker W, Bombelli M, Kinzl L. Unfall Chirurq. Springer−Variag 1993. 96:488−92 "Vakuumversiegelung zur Behandlung des Weichteilschadens bei offenen Frakturen." with English translation [Vacuum sealing as treatment of soft tissue damage in open fractures]. [German] NPL−
157
【非特許文献150】 Valenta, A.L. American Journal of Nursing. April 1994. "Using the Vacuum Dressing Alternative for Difficult Wounds." 94:44−5 NPL−414
【非特許文献151】 Saunders, J. W., The Lancet, pp. 1286−1287, June 28, 1952, "Negative−Pressure Device for Controlled Hypotension during Surgical Operations" NPL−356

【非特許文献152】 Landis, et al., Robinette Foundation of the Hospital of the University of Pennsylvania, "The Effects of Alternate Suction and Pressure on Blood Flow to the Lower Extremities" (September 1933). NPL−249
【非特許文献153】 Hargens et al., Space Physiology Laboratory, Life Science Division, NASA Ames Research Center, "Control of Circulatory Function in Altered Gravitational Fields" (February 1992). NPL−189
【非特許文献154】 Wolthuis et al, Physiological Reviews, 54: 566−595, July 1974, "Physiological Effects of Locally Applied Reduced Pressure in Man" NPL−441
【非特許文献155】 Viljanto et al., Br. J. Surg., 63: 427−430, 1976, "Local Hyperalimentation of Open Wounds" NPL−419
【非特許文献156】 Dillon, R. Angiology −− The Journal of Vascular Diseases, pp. 47−56, January 1986, "Treatment of Resistant Venous Stasis Ulcers and Dermatitis with the End−Diastolic Pneumatic Compression Boot" NPL−118
【非特許文献157】 Lundvall et al., Acta Physiol Scand, 136: 403−409, accepted Jan. 28, "Transmission of externally applied negative pressure to the underlying tissue. A study on the upper arm of man" NPL−262
【非特許文献158】 Klemp et al., The Journal of Investigative Dermatology, pp. 725−726 (1989), "Subcutaneous Blood Flow in Early Male Pattern Baldness" NPL−236
【非特許文献159】 A. Harle, Z. Orthop., 127: 513−517 (1989), "Schwachstellen herkommlicherDrainagen" with English Translation. NPL−192
【非特許文献160】 Dunlop et al., Br. J. Surg., 77: 562−563 (1990), "Vacuum drainage of groin wounds after vascular surgery: a controlled trail". NPL−125
【非特許文献161】 Maddin et al., International Journal of Dermatology, 29: 446−450 (1990), "The Biological Effects of a Pulsed Electrostatic Field with Specific Reference to Hair: Electrotrichogenesis" NPL−263
【非特許文献162】 Nakayama et al., Ann. Plast. Surg., 26:499−502 (1991), " A New Dressing Method for Free Skin Grafting in Hands" NPL−307
【非特許文献163】 Hargens et al., Aviation, Space and Environmental Medicine, pp. 934−937, Oct. 1991, "Lower Body Negative Pressure to Provide Load Bearing in Space" NPL188
【非特許文献164】 Author unknown, Science, Sept. 1992, p.42, "The Not−So−Bald−Truth" NPL−022
【非特許文献165】 Techno Takatsuki Co., Ltd., 8−16 Hatchonishimachi, Takatsuki City, Osaka, JAPAN, "HiBlow Air Pump" NPL−399
【非特許文献166】 Wells Johnson Company, 2045 N. Forbe Blvd., Suite 106, Tucson, AZ, "Suction Tips" NPL−432
【非特許文献167】 Industrial Equipment News, P.O. Box 1158, Skokie, IL 60076−9786, "Miscellaneous Equipment" NPL−218
【非特許文献168】 Letsou et al. "Stimulation of Adenylate Cyclase Activity in Cultured Endothelial Cells Subjected to Cyclic Stretch." Cardiovascular Surgery 3. Toronto. Sept. 1989. 634−639. NPL−253
【非特許文献169】 Bucalo et al. "Inhibition of Cell Proliferation by Chronic wound Fluid." Wound Repair and Regeneration. 181−186 July 1993 NPL−065
【非特許文献170】 Falange, Vincent. "Growth Factors and Chronic Wounds: The need to Understand the Microenvironment." Journal of Dermatology, Bol. 19: 667−672. 1992. NPL−148
【非特許文献171】 Urschel et al. "The Effect of Mechanical Stress on Soft and Hard Tissue Repair; a Review." British Journal of Plastic Surgery. 41, 182−186. 1988. NPL−411
【非特許文献172】 Gogia, Prem P. "The Biology of Wound Healing." Ostomy/Wound Management. Nov.−Dec. 1992. pp 12, 14−16, 18−20, 22 NPL−172
【非特許文献173】 Wysocki et al. "Wound Fluid from Chronic Leg Ulcers Contains Elevated Levels of Metalloproteinases MMP−2 and MMP−9." The Society for Investigative Dermatology, Inc. July 1993. 64−68 NPL−450
【非特許文献174】 Olenius et al. "Mitotic Activity in Expanded Human Skin." Plastic and Reconstructive Surgery." Feb. 1993. 213−216. NPL−318
【非特許文献175】 Mulder, G. D. et al. (eds.), Clinicians Pocket Guide to Chronic Wound Repair,
【非特許文献176】 Spartanburg, SC: Wound Healing Publications), 1991, pp. 54−55. NPL−317
【非特許文献177】 Chariker, M. E. et al. (eds), "Effective Management of Incisional and Cutaneous Fistulae with Closed Suction Wound Drainage," Contemporary Surgery, Vol. 34, June 1989, pp 59−63. NPL−073
【非特許文献178】 Rastgeldi, S.: I. Pressure Treatment of Peripheral Vascular Diseases. II. Intermittent Pressure Treatment of Peripheral Vascular Diseases. Opuscula Medica, Suppl. XXVII, 1972. NPL−343
【非特許文献179】 OP−Journal Nr. 3, Jahr. 6, Dec. 1990, pp 31−35 W. Fleischmann, M. Mentzel, L. Kinzl "BWS, Gefahren and Komplikationen der Therapie" with English Trans. NPL−156
【非特許文献180】 Zumtobel et al., (1991) "Wunddrainage in der Elektiveund Notfalichirurgie" Wolfgang Pabst Verlag, relevant page 12, left column. English Translation attached. NPL−455
【非特許文献181】 Saechtling, Kunststoff−Taschenbuch, 24. Ausgabe 1989, S. 439, 477. English Translation attached. NPL−350
【非特許文献182】 Mutschler, W. Bakker D. J., "Temporarer Hautersatz", ZFA 1989, Heft 24, S. 714−720 als Sonderdruck. English Translation attached. NPL−305
【非特許文献183】 W. Fleischmann, U. Becker, M. Bischoff, H. Hoekstra, "Vacuum sealing: indication, technique, and results", Eur. J. Orthop & Traumato (1995) 5:37−40. NPL−158
【非特許文献184】 Argenta LC, Morykwas MJ. Vacuum−assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997;38: 563−577 WFU−31
【非特許文献185】 Morykwas MJ, Argenta LC, Shelton−Brown El, McGuirt W. Vacuum−assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 1997; 38:553−62 WFU−29
【非特許文献186】 Davydov IA, Larichev AB, Smirnov AP, Flegontov VB. Vakuum−terapiia v lechenii ostrykh gnoinykh zabolevanii miagkikh tkanei I gnoinykh ran. [Vacuum therapy of acute suppurative diseases of soft tissues and suppurative wounds]. Russian Vestnik Khirurgii Imeni I − I − Grekova 1988; 141: 43−6 with Eng.Trans. DV10
【非特許文献187】 Davydov IA, Abramov Al, Larichev AB. Vakuum−terapiia v preduprezhdenii posleoperatsionnoi ranevoi infektsii. [Vacuum therapy in the prevention of postoperative wound infection]. Russian Vestnik Khirurgii Imen I − I − Grekova 1991; 147:91−5, with English Translation. DV12
【非特許文献188】 lankov NI. Simuliatsiia konsolidatsii perelomov nizhnei cheliusti vaktuumnoi terapiei. [Stimulation of consolidation of mandibular fractures by means of vacuum therapy] Russian. Stomatologiia 1971; 50: 86, with Eng. Trans. NPL217
【非特許文献189】 Inoiatov IM, Aleksandrov VB. Lechenie promezhnostnoi rany posle amputatsii priamoi kishki vakuum−aspiratsiei. [Vacuum aspiration in the treatment of the perineal wound following extirpation of the rectum]. Russian. Khirurgiia 1971; 47: 74−8, with English Translation. NPL−220
【非特許文献190】 Saechtling, Kunststoff−Taschenbuch, 24. Ausgabe 1989, S. 439, 477. English Translation attached. NPL−350
【非特許文献191】 Mutschler, W. Bakker D. J., "Temporarer Hautersatz", ZFA 1989, Heft 24, S. 714−720 als Sonderdruck. English Translation attached. NPL−305
【非特許文献192】 W. Fleischmann, U. Becker, M. Bischoff, H. Hoekstra, "Vacuum sealing: indication, technique, and results", Eur. J. Orthop & Traumato (1995) 5:37−40. NPL−158
【非特許文献193】 Argenta LC, Morykwas MJ. Vacuum−assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997;38: 563−577 WFU−31
【非特許文献194】 Morykwas MJ, Argenta LC, Shelton−Brown El, McGuirt W. Vacuum−assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 1997; 38:553−62 WFU−29
【非特許文献195】 Davydov IA, Larichev AB, Smirnov AP, Flegontov VB. Vakuum−terapiia v lechenii ostrykh gnoinykh zabolevanii miagkikh tkanei I gnoinykh ran. [Vacuum therapy of acute suppurative diseases of soft tissues and suppurative wounds]. Russian Vestnik Khirurgii Imeni I − I − Grekova 1988; 141: 43−6 with Eng.Trans. DV10
【非特許文献196】 Davydov IA, Abramov Al, Larichev AB. Vakuum−terapiia v preduprezhdenii posleoperatsionnoi ranevoi infektsii. [Vacuum therapy in the prevention of postoperative wound infection]. Russian Vestnik Khirurgii Imen I − I − Grekova 1991; 147:91−5, with English Translation. DV12
【非特許文献197】 lankov NI. Simuliatsiia konsolidatsii perelomov nizhnei cheliusti vaktuumnoi terapiei. [Stimulation of consolidation of mandibular fractures by means of vacuum therapy] Russian. Stomatologiia 1971; 50: 86, with Eng. Trans. NPL217
【非特許文献198】 Inoiatov IM, Aleksandrov VB. Lechenie promezhnostnoi rany posle amputatsii priamoi kishki vakuum−aspiratsiei. [Vacuum aspiration in the treatment of the perineal wound following extirpation of the rectum]. Russian. Khirurgiia 1971; 47: 74−8, with English Translation. NPL−220
【非特許文献199】 Kochnev VA. Primenenie vakuum−drenazhnoi sistemy dlia profilaktiki posleoperatsionnykh ranevykh oslozhnenii u bolnykh opukholiami. [The use of a vacuum drainage system in the prevention of postoperative wound complications in tumor patients]. Russian. Voprosy Onkologii 1967; 13:102−5, w/Eng. Trans. NPL−239
【非特許文献200】 Mirazimov BM. Svobodnaia Kozhnaie plastika stopy s podgotovkoi ranevoi poverkhnosti vakumiravaniem [Free skin graft of the foot with vacuum preparation of the wound surface]. Russian. Orthopediia Travmatologiia I Protezirovanie 1966;27:19−22, with English Translation. NPL−291
【非特許文献201】 Mirazimov BM, Vasina TA, Mezhericher MI. Mikroflora dlitelno nekazhivaiushchikh ran i effektivnost metoda vakuumirovaniia. [Microflora of prolonged non−healing wounds and the effectiveness of the vacuum evaporative method]. Russian. Khirurgiia 1967; 43: 40−3, with English Translation. NPL−290
【非特許文献202】 Mirazimov BM. Vorbereitung von Wunden und Geschwuren zur Hautplastik unter Anwendung der Vakuumierung [Preparation of wounds and abcesses for dermatoplasty by means of a vacuum device]. German. Beitrage zur Orthopadie und Traumatologie 1967; 14:224−30, with Eng. Translation. NPL−292
【非特許文献203】 Netudykhatka 0. Vliianie nizkogo dozirovannogo vakuuma na techenie reparativnogo protsessa v kostnoi tkani [Effect of low vacuum on the course of the reparative process in bone tissue]. Russian. Voprosy Kurortologii, Fizioterapii i Lechebnoi Fizicheskoi Kultury 1972; 37:411−5, w/Eng. Trans. NPL311
【非特許文献204】 Volkov LA. Isporzovanie vakuum−drenazhnoi sistemy v khirurgicheskoi praktike. [Use of vacuum−drainage system in surgical practice]. Russian. Klinicheskaia Khirurgiia. 1973;7:54−5, with English Translation. NPL−423
【非特許文献205】 Teder H, Sanden G, Svedman P. Continuous Wound Irrigation in the Pig. J Invest Surg 1990;3:399−407 NPL−400
【非特許文献206】 Nakayama Y, Tomotari I, Soeda S. A New Method for the Dressing of Free Skin Grafts. Plast Reconstr Surg 1990;86:1216−1219 NPL−308
【非特許文献207】 Brock WB, Barker DE, Burns RP. Temporary Closure of open abdominal wounds: the vacuum pack. Amer Surg 1995;61:30−5 NPL−059
【非特許文献208】 Shein M, Saadia R, Jameson JR, Decker GAG. The "sandwich technique" in the Management of the Open Abdomen. Br J Surg 1986;73:369−70 NPL−363
【非特許文献209】 Broome A. Hansson L, Lundgren F, Smedberg S. Open Treatment of Abdominal Septic Catastrophies. World J. Surg 1983;7:792−6 NPL−061
【非特許文献210】 Vatanasapt V, Areemit S, Jeeravipoolvarn P, et al. Red rubber bulb, cheap and effective vacuum drainage. Journal of the Medical Association of Thailand 1989;72:193−7 NPL−417
【非特許文献211】 Brummelkamp WH, Taat CW, Slors JF. High−vacuum drainage and primary perineal wound closure in abdominoperineal excision of the rectum. Netherlands Journal of Surgery 1991;43:236−9 NPL−063
【非特許文献212】 Morykwas J, Argenta LC. Nonsurgical modalities to enhance healing and care of soft tissue wounds. Journal of the Southern Orthopaedic Association 1997;6:279−88 WFU−04
【非特許文献213】 Sames CP. Sealing of wounds with vacuum drainage [letter] Br Med J 1977;2:1123 NPL−353
【非特許文献214】 Greer SE, Longaker MT, Margiotta M. Preliminary Results from a Multicenter, Randomized, Controlled, Study of the Use of Subatmospheric Pressure Dressing for Pressure Ulcer Healing. Wound Repair and Regeneration 1999;7:255 NPL087
【非特許文献215】 Greer SE, Longaker MT, Margiotta M, Matthews AJ, Kasabian A. The Use of Subatmospheric Pressure Dressing for the Coverage of Radial Forearm Free Flap Donor−Site Exposed Tendon Complications. Ann Plast Surg 1999;43:551554 NPL−179
【非特許文献216】 Greer SE, Duthie E, Cartolano B, Koehler KM, Maydick−Youngberg D, Longaker MT. Techniques for Applying Subatmospheric Pressure Dressing to Wounds in Difficult Regions of Anatomy. JWOCN 1999;26:250−3 NPL−177
【非特許文献217】 Greer SE, Kasabian A, Thorne C, Borud L, Sims CD, Hsu M. The Use of Subatmospheric Pressure Dressing to Salvage a Gustilo Grade IIIB Open Tibia Fracture with Concomitant Osteomyelitis and Avert a Free Flap. Ann Plast Surg 1998;41:687 NPL−178
【非特許文献218】 Genecov DG, Schneider AM, Morykwas MJ, et al. A Controlled subatmospheric pressure dressing increases the rate of skin graft donor site reepithelialization. Ann Plast Surg 1998;40:219−25 WFU−28
【非特許文献219】 Mendez−Eastman S. Negative pressure wound therapy. Plastic Surgical Nursing 1998;18:27−9, 33−37 NPL−277
【非特許文献220】 Banwell P. Withey S, Holten I. The use of negative pressure to promote healing [letter; comment]. Brit J Plast Surg 1998;51:79 NPL−033
【非特許文献221】 Blackburn J H Boemi L, Hall WW. et al. Negative−pressure dressings as a bolster for skin grafts. Ann Plast Surg 1998;40:453−7 NPL−049
【非特許文献222】 Smith LA, Barker DE, Chase CW, et al. Vacuum Pack Technique of Temporary Abdominal Closure: A Four−Year Experience. Amer Surg 1997;63:1102−8 NPL378
【非特許文献223】 McCulloch JM, Kemper CC. Vacuum−Compression Therapy for the Treatment of an lschemic Ulcer. Physical Therapy 1993;73:165−9 NPL−270
【非特許文献224】 Muliner T, Mrkonjic L, Kwasny 0, Vecsei V. The use of negative pressure to promote the healing of tissue defects: a clinical trial using the vacuum sealing technique [see comments]. Brit J Plast Surg 1997;50:194−9 NPL−302
【非特許文献225】 Mirazimov, B.M.: Free Skin Grafting of Wounds and Ulcers using the "Vacuum Treatment" Method. [Orthop. Travmatol. Protez., 28(1):54−58.] with English Trans. 1967 NPL−293
【非特許文献226】 Greer, Steven E., "Whither Subatmospheric Pressure Dressing?" The Institute of Reconstructive Plastic Surgery, The New York University Medical Center, New York, NY April Issue of Annals of Plastic Surgery 2000. NPL−180
【非特許文献227】 Registration Number 1982349. Owner, KCI Inc., 3440 E. Houston Street San Antonio TEXAS 78219. Source: United States Patent and Trademark Office official website. Filing date 05/01/1995 Registration Date 06/25/1996 NPL−344
【非特許文献228】 Hidden Interest - A Special Report.; When Physicians Double as Entrepreneurs. The New York Times. llpp. November 30, 1999 NPL−133
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【非特許文献230】 Morykwas, Michael J., et al., "Use of Subatmospheric Pressure to Prevent Progression of Partial−Thickness Burns in a Swine Model". Journal of Burn Care & Rehabilitation 20 (1 Part 1): 15−21 (1999) WFU−03
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【非特許文献232】 Rosser, Charles J., et al., "A New Technique to Manage Perineal Wounds". Infections in Urology 13(2) 45−47, 56 (2000). WFU−34
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【非特許文献234】 Meara, John G., et al., " Vacuum−Assisted Closure in the Treatment of Degloving Injuries". Annals of Plastic Surgery 42(6) 589−594 (1999). NPL−273
【非特許文献235】 Obdeijn, Miryam C., et al., "Vacuum−Assisted Closure in the Treatment of Poststernotomy Mediastinitis". Ann Thorac Surgery 68 2358−60 (1999). NPL315
【非特許文献236】 Mendez−Eastman, Susan., "When wounds wont heal". RN 20−24 (1998) NPL282
【非特許文献237】 Hartnett, Jacqueline M., "Use of Vacuum−Assisted Wound Closure in Three Chronic Wounds". JWOCN 25 (6) 281−290 (1998). NPL−195
【非特許文献238】 Mendez−Eastman, Susan., "Use of Hyperbaric Oxygen and Negative Pressure Therapy in the Multidisciplinary Care of a Patient with Nonhealing Wounds". JWOCN 26(2) 67−76 (1999). NPL−281
【非特許文献239】 Mendez−Eastman, Susan., "Use of Hyperbaric Oxygen and Negative Pressure Therapy in the Multidisciplinary Care of a Patient with Nonhealing Wounds". JWOCN 26(2) 67−76 (1999). NPL−281
【非特許文献240】 Davydov, et al., "Pathenogenic mechanism of the effect of vacuum therapy on the course of the wound process". Khirurgiia, June 1990 (with English translation). DV13
【非特許文献241】 Davydov, et al., "Vacuum therapy in the treatment of suppurative lactation mastitis". Vestn. Khir., Nov. 1986 (with English translation). DV8
【非特許文献242】 Davydov, et al., "Bacteriological and cytological evaluation of the vacuum therapy of suppurative wounds". Vestn. Khir., Oct. 1988 (with English translation). DV2
【非特許文献243】 Davydov, et al., "Basis of the use of forced early secondary suture in the treatment of suppurative wounds by the vacuum therapy method". Vestn. Khir., Mar. 1990 (with English translation). DV1
【非特許文献244】 Borzov, et al., "Vacuum therapy of some skin diseases". Vestn. Dermatol. Venerol., Aug. 1965 (with English translation). NPL−055
【非特許文献245】 M.J. Morykwas and L.C. Argenta, "Techniques in Use of V.A.C. Treatment (in English)", Acta Chir. Austriaca Supplement Nr. 150, 1998, p. 3−4 of 2−28. WFU02
【非特許文献246】 Garcia−Rinaldi, et al., "Improving the Efficiency of Wound Drainage Catheters", J. Surg., 1975, pp. 372−373. NPL−169
【非特許文献247】 Raffl, et al. "The Five Year Survival Rate for Gastric Cancer: Statistical Study from Syracuse Medical Center", Cancer, 6:756−759, July 1953. NPL−339
【非特許文献248】 Raffl, et al., "The Use of Negative Pressure Under Skin Flaps After Radical Mastectomy, Ann. Surg. 136: 1048, December, 1952. NPL−340
【非特許文献249】 Marie Knight, "A Second Skin for Patients with Large Drainage Wounds," Nursing 6(1) p. 37, 1976. NPL−238
【非特許文献250】 Oscar Ramirez, "Optimal Wound Healing under Op−Site Dressing" Plas. & Recon. Surg., 73(3): 474−475; 1984. NPL−341
【非特許文献251】 Helen Bibleheiner, "Dealing with a Wound that Drains 1.5 Liters per Day," RN August 1986. NPL−046
【非特許文献252】 Peter Schwab, "Primary Closure of the Perineal Wound After Proctectomy" Mayo Clin. Proc., March 1974, Vol. 49. NPL−362
【非特許文献253】 SVEDMAN, P., et al., "Staphylococcal wound infection in the pig: Part I. Course," Ann. Plast. Surg., 23(3):212−218, (September 1989). NPL−684
【非特許文献254】 SANDEN, G., et al., "Staphylococcal wound infection in the pig: Part II. Inoculation, quantification of bacteria, and reproducibility," Ann. Plast. Surg., 23(3):219−223, (September 1989). NPL−685
【非特許文献255】 Avery, C., et al., "Negative pressure wound dressing of the radial forearm donor site",
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【非特許文献256】 Armstrong, David G., et al., "Outcomes of Subatmospheric Pressure Dressing Therapy on Wounds of the Diabetic Foot", Ostomy/Wound Management 2002; 48(4): 64−68. NPL−019
【非特許文献257】 Brown, Karen M., et al., "Vacuum−Assisted Closure in the Treatment of a 9−Year−Old Child with Severe and Multiple Dog Bite Injuries of the Thorax", Society of Thoracic Surgeons, 2001; 72:1409−1410. NPL−062
【非特許文献258】 Catarino, Pedro A., et al., "High−Pressure Suction Drainage via a Polyurethane Foam in the
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【非特許文献259】 Mendez−Eastman, Susan, RN, CPSN, CWCN, Clinical Management Extra, Guidelines for Using Negative Pressure Wound Therapy, Advances in Skin & Wound Care, November/December 2001, Vol. 14, No. 6, p. 314−323. NPL−278, NPL−686
【非特許文献260】 Cooper, Susan Mary, "Topical negative pressure in the treatment of pressure ulcers", Letters posted in the Journal of the American Acad of Dermatology, August, Part 1, 1999, p. 280. NPL099
【非特許文献261】 Davydov, I.A., et al., "Concept of clinico−biological control of the wound", Vestnik khirurgii imeni 1.1. Grekova, v. 146, issue 2, 1991, 132−6 (with English translation). DV5
【非特許文献262】 de la Torre, Jorge I., MD, et al., "Healing a Wound with an Exposed Herrington Road: A Case Study", Ostomy Wound Management, pgs. 18 −19, May 2002, Vol. 48, Issue 5. NPL−108
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【非特許文献266】 Evans, D. and Land, L., "Topical negative pressure for treating chronic wounds: a systematic review", British Journal of Plastic Surgery (2001), 54, 238−242. NPL−144
【非特許文献267】 Fabian, Thaddeus S., MD, "The Evaluation of Subatmospheric Pressure and Hyperbaric Oxygen in Ischemic Full−Thickness Wound Healing" , The American Surgeon, December 2000, Vol.. 66, 1136−1143. NPL−146
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【非特許文献269】 Giovannini, Uberto M., MD, "Negative Pressure for the Management of an Exposed Vascular Dacron Polyester Patch", Annals of Plastic Surgery, 47(5): 577−578, 2001. NPL−171
【非特許文献270】 Gustafsson, Ronny, MD, "Vacuum−assisted closure therapy guided by C−reactive protein level in patients with deep sternal wound infection", The Journal of Thoracic and Cardiovascular Surgery, Vol. 123, No. 5, pgs. 895−900, May 2002. NPL−181
【非特許文献271】 Gwan−Nulla, Daniel N., MD and Casal, Rolando S., MD, "Toxic Shock Syndrome Associated with the Use of the Vacuum−Assisted Closure Device", Ann Plastic Surgery 2001;47:552−554. NPL183
【非特許文献272】 Hersh, Robert E., MD, et al., "The Vacuum−Assisted Closure Device as a Bridge to Sternal Wound Closure", Ann Plast Surg. 2001; 46: 250−254. NPL−203
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【非特許文献369】 Part III. Resolving Selected Clinical Dilemmas, pp. 17−20. NPL−328
【非特許文献370】 "Making Sense of Wound Drainage", Nursing Times, July 5, 1989, pp. 40−42, vol. 85, no. 27. NPL−265
【非特許文献371】 Manualectric Breastpump, Catalog pages (4 pages), diagrams and descriptions. NPL266
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【非特許文献374】 OpSite Wound Dressings, "Do Your Pressure Sore Dressings Shape Up to the OpSite Standard", 2 pages of advertisements. NPL−319
【非特許文献375】 Dow Corning Silastic(r) Foam Dressing: A New Concept in the Management of Open Granulating Wounds, 2 pages of advertisements. NPL−121
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【非特許文献382】 Paradise Valley Hospital, The Center for Wound Healing and Hyperbaric Medicine, 3 pages of brochure. NPL−326
【非特許文献383】 DuoDERM HydroactiveTM Dressing, "In wound management −− Now, a proven environment for fast healing", 1 page advertisement. NPL−126
【非特許文献384】 Howmedica porto−vac(r), "Gentle, Steady Wound Drainage", 1 page advertisement. NPL−212
【非特許文献385】 Silicone from CUI (Cox−Uphoff International), "Flexability", 1 page advertisement. NPL−371
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【非特許文献398】 COOK PNEUMOTHORAX CATHETER SET, WAYNE PNEUMOTHORAX CATHETER SET, Emergency Medicine, Videotape advertisement. NPL−094
【非特許文献399】 SCHAFFER, D., "Closed Suction", Nursing97, Nov., http://www.springnet.com, pp. 62−64. NPL−357
【非特許文献400】 CARROLL, P., "The Principles of Vacuum and Its Use in the Hospital Environment", Ohmeda, pp 1−30 and cover sheet. NPL−070
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【非特許文献404】 MULDER, G.D, et al., Clinicians Pocket Guide to Chronic Wound Repair, Wound Healing Publications Second Edition, 1992, pp. 1−107. NPL−300
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【非特許文献407】 Proceedings from the 2003 National V.A.C.(r) Education Conference, supplement to the April 2004 WOUNDS, 40 pages. NPL−335
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【非特許文献413】 ERDMANN, D., et al., "Abdominal Wall Defect and Enterocutaneous Fistula Treatment with the Vacuum−Assisted Closure (V.A.C.) System", Plastic and Reconstructive Surgery, Vol. 108, No. 7, pp. 2066−2068 (December 2001). NPL−141
【非特許文献414】 LOHMAN, R., et al., "DISCUSSION: Vacuum Assisted Closure: Microdeformations of Wounds and Cell Proliferation", Plastic and Reconstructive Surgery, October 2004, pp. 1097−1098. NPL−257
【非特許文献415】 DEFRANZO, A.J., et al., "109: Use of Sub−Atmospheric Pressure for Treatment of Gunshot Injuries", Plastic Surgical Forum, V. XXIII, Los Angeles, CA, October 14−18, 2000, pp. 180−181. WFU−05
【非特許文献416】 MARKS, M., et al., "Management of Complex Soft Tissue Defects in Pediatric Patients Using the V.A.C. Wound Closure", Plastic Surgical Forum, V. XXI, Boston, MA, October 3−7, 1998, pp. 215−216. WFU−09
【非特許文献417】 MORYKWAS, M. and ARGENTA, L., "Use of Negative Pressure to Prevent Progression of Partial Thickness Burns", American Burn Association, V. 26, 26th Annual Meeting, April 20−23, 1994, Orlando, Florida, pp. 157. WFU−14
【非特許文献418】 MORYKWAS, M. and ARGENTA, L., "Vacuum Assisted Closure (VAC Therapy) for Secondary Closure of Dehisced and Infected Wounds", Wound Repair and Regeneration, July−September, 1995, pp. 361. WFU−11
【非特許文献419】 MORYKWAS, M. and ARGENTA, L., "Treatment of Burned Extremities Using Vacuum Therapy (The V.A.C.)", Wound Repair and Regeneration, V. 3, N. 3, July − September, 1995, pp. 367. WFU−15
【非特許文献420】 WEBB, L. and MORYKWAS, M., et al., "The Use of Vacuum−Assisted Closure in Composite Wound Management", The Third Riva Congress, Current Perspectives in Fracture Management and Orthopaedic Reconstruction, May 10−14, 2000, Italy, pp. 137. WFU−20
【非特許文献421】 ARGENTA, L., et al., "Use of V.A.C. for Treatment of Dehisced Sternal Incisions", Plastic Surgical Forum, V. XXIII, Los Angeles, CA, Oct. 14−18, 2000, pp. 172−174. WFU−06
【非特許文献422】 MORYKWAS, M., et al., "Isolated Muscle Flap Survival with Complete Venous Occlusion: Varying Delay in External Application of Sub−atmospheric Pressure", Plastic Surgical Forum, V. XXI, Boston, MA, Oct. 3−7, 1998, pp. 237. WFU−16
【非特許文献423】 MORYKWAS, M. and ARGENTA, L., "V.A.C. Experience and Difficult Wounds", des Journees Regionales des Plaies et Cicatrisations", Sept. 22−23, 1997, pp. 76−90. WFU−01
【非特許文献424】 MORYKWAS, M. and ARGENTA, L., "Use of the V.A.C.TM For Treatment of a Traumatic Left Hip Disarticulation",ACA−Acta Chir. Austriaca, Supplement Nr. 150, 1998, pp. 24−25 and cover sheet. WFU−12
【非特許文献425】 BANWELL, P., et al., "Application of Topical Sub−Atmospheric Pressure Modulates Inflammatory Cell Extravasation in Experimental Partial Thickness Burns", Wound Repair and Regeneration, July/August, 1999, V. 7, N. 4, pp. A286−287. WFU−08
【非特許文献426】 BANWELL, P., et al., "Dermal Perfusion in Experimental Partial Thickness Burns: The Effect of Topical Subatmospheric Pressure", Jan/Feb 2000, V. 21, N. 1, Part 2, Burn Care & Rehabilitation. WFU−07
【非特許文献427】 MORYKWAS, M., et al., "The Effect of Externally Applied Subatmospheric Pressure on Serum Myoglobin Levels After a Prolonged Crused/Ischemia Injury", The Journal of TRAUMA Injury, Infection and Critical Care, Sept. 2002, V. 53, N.3, pp. 537−540. WFU−19
【非特許文献428】 MOLNAR, J., et al., "Acceleration of Integra Incorporation in Complex Tissue Defects with Subatmospheric Pressure", Plastic and Reconstructive Surgery, April 15, 2004, pp. 1339−1346. WFU−10
【非特許文献429】 DEFRANZO, A.J., et al., "The Use of Vacuum−Assisted Closure Therapy for the Treatment of Lower−Extremity Wounds with Exposed Bone", Plastic and Reconstructive Surgery, October, 2001, V. 108, N. 5, pp. 1184−1191. WFU−25
【非特許文献430】 MORYKWAS, M., "The Use of The V.A.C. Wound Treatment System for Acute and Subacute Wounds", Plaies & Cicatrices, Would Closure Healing, April 21, 22 and 23, 1999. WFU−17
【非特許文献431】 WEBB, L., et al., "Negative Pressure Wound Therapy in the Management of Orthopedic Wounds", Ostomy Wound Management, April 2004, V. 50, Issue 4A (Suppl), pp. 26−27 and cover sheet. WFU−22
【非特許文献432】 WEBB, L., et al., "Wound Management With Vacuum Therapy", English abstract from website printout and German article, http://www.ncbi.nlm.liih.eovientrez/querylcai?cmd=Retrieve12/2/2004, 2 pages website printout, German article, October 2001, pp. 918−926. WFU−23
【非特許文献433】 MORYKWAS, M. and ARGENTA, L., "Sub−Atmospheric Pressure Wound Treatment and Cultured Keratinocyte Allografts", Cultured Human Keratinocytes and Tissue Engineered Skin Substitutes", 02001 Georg Thieme Verlag, pp. 343−346. WFU−27
【非特許文献434】 MOLNAR, J., et al., "Single−Stage Approach to Skin Grafting the Exposed Skull", Plastic and Reconstructive Surgery, Jan. 2000, V. 105, N. 1, 174−177. WFU−32
【非特許文献435】 SCHERER, L, et al., "The Vacuum Assisted Closure Device: A Method of Securing Skin Grafts and Improving Graft Surival", Arch. Surg., V. 137, Aug. 2002, pp. 930−934. NPL−359
【非特許文献436】 MILLER, P., et al., "Late Fascial Closure in Lieu of Ventral Hernia: The Next Step in Open Abdomen Management", the Journal of TRAUMA Injury, Infection and Critical Care, Nov. 2002, V. 53, N. 5, pp. 843− 849. NPL−288
【非特許文献437】 BETANCOURT, S., "A Method of Collecting the Effluent From Complicated Fistula of the Small Intestine", 1986, p. 375. NPL−045
【非特許文献438】 DORLANDS Illustrated Medical Dictionary , Twenty−Fifth Edition, 1974, pp. 1112. NPL−120
【非特許文献439】 HOPF, H., et al., "Adjuncts to preparing wounds for closure Hyperbaric oxygen, growth factors, skin substitutes, negative pressure wound therapy (vacuum−assisted closure)", Foot Ankle Clin N Am 6, 2001, pp. 661−682. NPL−211
【非特許文献440】 CHARIKER−JETER(r) Wound Drainage Kit, BlueSky Medical, 2 page advertisement with copy of business card from Quality Medical Supply. NPL−077
【非特許文献441】 CHARIKER−JETER(r) Wound Drainage Kit Instructions, Item #500.7777, BlueSky Medical, 2 pages. NPL076
【非特許文献442】 WOODING−SCOTT(r) Wound Drainage Kit Contents, Item #500.8888, 1 page. NPL−445
【非特許文献443】 MONTGOMERY, B., "Easy Dressing of Large, Draining Abdominal Wounds Using Moisture Vapor−Permeable Film", pp. 417−418, Techniques for Surgeons, Wiley Medical Publication, (c)1985. NPL−297
【非特許文献444】 HERRMANN, L., et al., "The Pavaex (Passive Vascular Exercise) Treatment of Obliterative Arterial Diseases of the Extremeties", The Journal of Medicine, December 1933, pp. 524−529. NPL−200
【非特許文献445】 HERRMANN, L., et al., "Passive Vascular Exercises: Treatment of Peripheral Obliterative Arterial Diseases by Rhythmic Alternation of Environmental Pressure", Archives of Surgery, v. 29, n. 5, November 1934, pp. 697−704. NPL−198
【非特許文献446】 STURR, R., "Evaluation of Treatment of Peripheral Vascular Disease by Alternating Positive and Negative Pressure, Philadelphia, Archives of Physical Therapy, Sept. 1938, pp. 539−543. NPL−392
【非特許文献447】 BALIN, A., et al., "Oxygen Modulates Growth of Human Cells at Physiologic Partial Pressures", Laboratory for Investigative Dermatology, J. Exp. Med.(c), the Rockefeller University Press, v. 160, July 1984, pp. 152166. NPL−029
【非特許文献448】 SARAN RESINS AND FILMS, "Fresh Thinking". website printout, 6 pages, January 20, 2004. NPL−354
【非特許文献449】 BLUESKY MEDICAL, "A Leader in Suction Technology − Wound Drainage Experts", printout of website, 55 pages, April 8, 2003, www.blueskvmedical.com. NPL−052
【非特許文献450】 DAVYDOV, et al., "Would Healing Under the Conditions of Vacuum Draining", Khirurgiia (Mosk). 1992, (78): 21−6 (with English translation by Scientific Translation Services). DV14
【非特許文献451】 COYLE, M., et al., "A CASE STUDY: Positive Outcomes to Negative Pressure Wound Therapy − A collaborative assessment", Hospital of Saint Raphael, 1 page chart. NPL−102
【非特許文献452】 NEMOTO, H., et al., "Stories From the Bedside: Purple Urine Bage Syndrome Development in Ileal Conduit", WCET, Journal 23(2), pp. 31−34. NPL−310
【非特許文献453】 BAKER, B., "Negative−Pressure Therapy Looks Promising", Skin & Allergy News, February 2000, p. 14. NPL−028
【非特許文献454】 McCALLON, S., et al., "Vacuum−Assisted Closure versus Saline−Moistened Gauze in the Healing of Postoperative Diabetic Foot Wounds", Ostomy Wound Management, August 2000, v.46, Issue 8.pp. 28−29, 31−32, 34. NPL−269
【非特許文献455】 Murray, J., et al., "On the Local and General Influence on the Body if Increased and Diminished Atmospheric Pressure", The Lancet, V. 1, 1834−1835, pp. 909−917. NPL−303
【非特許文献456】 HERRMANN, L., et al., "The Conservative Treatment of Arteriosclerotic Peripheral Vascular Diseases", pp. 750−760 (October 1934). NPL−199
【非特許文献457】 Versatile 1 Wound Vacuum SystemTM for The Promotion of Wound Healing, Wound Application instructions, 1 page advertisement. NPL−418
【非特許文献458】 Bluesky Medical "The Versatile One!TM", Wound Drainage and More, 1 page advertisement. (Labeled Spring 2003). NPL−050
【非特許文献459】 CHARIKER−JETER Wound Sealing Kit Would Application Instructions, 1 page advertisement NPL−078
【非特許文献460】 DAVIES , J.W.L, "Synthetic materials for covering burn wounds: Progress towards perfection. Part I. Short term dressing materials", Burns, 1983, Nov;10(2), 94−103. NPL−107 4
【非特許文献461】 LAMKE, L.O., et al., "The evaporative water loss from burns and the water−vapour permeability of grafts and artificial membranes used in the treatment of burns", Burns, 3, 159−165, 1977. NPL−247
【非特許文献462】 BARNETT, A., et al., "Comparison of Synthetic Adhesive Moisture Vapor Permeable and Fine Mesh Gauze Dressings for Split−Thickness Skin Graft Donor Sites", The American Journal of Surgery, Vol. 145, March 1983, pp. 379−381. NPL−038
【非特許文献463】 ALPER, J., et. al., "Moist wound healing under a vapor permeable membrane", Journal of the American Academy of Dermatology, Vol. 8, No. 3, March, 1983, pp. 347−353. NPL−012
【非特許文献464】 JAMES, J.H., et. al., "The use of Opsite, A Vapour Permeable Dressing, on Skin Donor Sites", British Journal of Plastic Surgery (1975), 28, 107−110. NPL−222
【非特許文献465】 NAHAS, L.F., et al., "Use of Semipermeable Polyurethane Membrane for Skin Graft Dressings", Plastic and Reconstructive Surgery, June 1981, pp. 791−792. NPL−306
【非特許文献466】 Edlich, R.F., et al., "Surgical Devices in Wound Healing Management", Wound Healing Biochemical & Clinical Aspects, W.B. Saunders Company, (c) 1992, pp. 581−599. NPL−131
【非特許文献467】 ORR, RK, et al., "Early Discharge After Mastectomy. A Safe Way of Diminishing Hospital Cost", Am Surg. 1987 March; 53(3) Abstract. NPL−322
【非特許文献468】 OTOLARYNGOLOGY, Head and Neck Surgery, The C.V. Mosby Company, (c) 1986, pp.1716, 1724 and 2521. NPL−324
【非特許文献460】 OTOLARYNGOLOGY, Volume III, Head and Neck, W.B. Saunders Company, (c)1980, pp. 2963. NPL−325
【非特許文献470】 LORE, JR., J.M., "An Atlas of Head and Neck Surgery", Second Edition, Volume II, W.B. Saunders Company, 0 1973. NPL−258
【非特許文献471】 Johnson, Frank E., "An Improved Technique for Skin Graft Placement Using A Suction Drain", pp. 585−586 (December 1984). NPL−226
【非特許文献472】 Dewan, P.A., et al., "An Alternative Approach To Skin Graft Donor Site Dressing", Aust. N.Z. J. Surg. 1986, 56, 509−510. NPL−116
【非特許文献473】 Kinetic Concepts, Inc., et al., v. Bluesky Medical Corporation, et al., Civil Action No. SA−03−CA−0832−RF, U.S. District Court, W. Dist. of Texas San Antonio Div., Promotional Slide Presentation BlueSky Medical Negative Pressure Wound Care with Versatile 1 Presentation Presented by Penny Campbell and Shelly Burdette−Taylor 27 pages (dated October 14, 2005). NPL−067
【非特許文献474】 Barillo, D., et al., "Management of Burns to the Hand", Wounds 15,(1):4−9, 2003 Health Management Publications, Inc., Posted 02/12/2003. NPL−037
【非特許文献475】 Medical Technology & Innovation, "Medical Technology is Extending Life, Reducing Costs", Vol 1, Issue 46, December 4, 2000. NPL−275
【非特許文献476】 Wu, Lisa C., et al., "Vacuum−Assisted Closure for the Treatment of Sternal Wounds: The Bridge Between Debridement and Defmitive Closure", printout from www.plasticsurgerv.org., 3 pages (printout dated April20, 2005). NPL−448
【非特許文献477】 Berton, A., "Management of Exuberant Granulation Tissue", Wound Management, pp. 551−562 (December 1989). NPL−043
【非特許文献478】 Tabers Cyclopedic Medical Dictionary, Edition 18, pps, 937, 942 and 1375. NPL−394
【非特許文献479】 Harris, Ann, et al., "Hypergranulation Tissue: a Nontraumatic Method of Management", Ostomy/Would Management, Vol.40, No. 5, June 1994. NPL−193
【非特許文献480】 Websters New Universal Unabridged Dictionary Deluxe Second Edition, page 631. NPL−431
【非特許文献481】 Chariker−Jeter Technique Tutorial by Penny E. Campbell, Wound Care Solutions, 1 page tutorial chart. NPL075
【非特許文献482】 Bluesky Medical, Negative Pressure Wound Therapy, Product Catalog Fall 2005, "Finally a choice..." 8 pages. NPL−053
【非特許文献483】 Chariker−Jeter Status Link from the website www.trademark.com/cbi−bin/tmlist. October 14, 2005, 1 page.NPL−074
【非特許文献484】 Bluesky Medical Support, printout of webpages www.woundvacuum.com/Standard%20Pages/sunvort.htm,October 11, 2005, pages 1−3. NPL−051
【非特許文献485】 Healing of Full Thickness Defects in Swine NPL−197
【非特許文献486】 Webster, J.G., "Prevention of Pressure Sores", 010P Publishing Ltd 1991, The Adam Hilger Series on Biomedical Engineering, pp. 199−223. NPL−430
【非特許文献487】 Garcia−Velasco, M., et al., "Compression Treatment of Hypertrophic Scars in Burned Children", The Canadian Journal of Surgery, V.21, No. 5, September 1978, pp. 450−452. NPL−170
【非特許文献488】 Rose, M.P., et al., "The Clinical Use Of A Tubular Compression Bandage, Tubigrip, for Bum−Scar Therapy: A Critical Anaylis", Burns (1985) 12, 58−64. NPL−347
【非特許文献489】 Murray, Y., "Tradition Rather Than Cure", Wound Care, Nursing Times, September 21, Vol. 84, No. 38, 1988. NPL−304
【非特許文献490】 SPURLOCK, Gareth, "The Management of Open Joint Injuries", Wound Management, Veterinary Clinics of North American Equina Practice, Vol. 5, No. 3, December 1989. NPL−386
【非特許文献491】 TITTEL, K., et at., "VariDyne - new standards in postoperative wound drainge", Jahrgang 14 (1988), Nr. 2, April, vol. 14 (1988), No. 2, April, pp. 104−107. NPL−403
【非特許文献492】 QUEEN, D., et al., "The preclinical evaluation of the Water Vapour Transmission Rate Through Burn Wound Dressings", Biomaterials 1987 Vol. 8, September, pp. 367−371. NPL−337
【非特許文献493】 WOOD, R.A.B., et al., "Foam Elastomer Dressing in the Management of Open Granulating Wounds: Experience with 250 Patients", Br. J. Surg., Vol. 64 (1977) , pp 554−557. NPL−443
【非特許文献494】 WAYMACK, J.P., et al., "An Evaulation of Aquaphor Gauze Dressing in Burned Children", Burns (1986) 12, 443−448. NPL−428
【非特許文献495】 WINTER, George D., "Epidermal Wound Healing Under a New Polyurethane Foam Dressing (Lyofoam)",
Plastic & Reconstructive Surgery, November 1975, Vo. 56, No. 5, pp. 531−537. NPL−438
【非特許文献496】 THOMAS, S., et al., "Comparative Review of the Properties of Six Semipermeable Film Dressings", The Pharmaceutical Journal, June 18, 1988, pp. 785−789. NPL−402
【非特許文献497】 BAKER, B., "Abundance of Web Sites on Wound Care Management", Family Practice News, March 1, 2000, pp. 52. NPL−027
【非特許文献498】 COSKER, T., et al., "Choice of Dressing Has a Major Impact on Blistering and Healing Outcomes in Orthopaedic Patients", Journal of Wound Care, Vo. 14, No. 1, January 2005, pp. 27−29. NPL−101
【非特許文献499】 TOWNSEND, P.L.G., "The Quest For A Cheap and Painless Donor−Site Dressing", Burns, 2, pp. 82−85 (January 1976). NPL−404
【非特許文献500】 LANGWORTHY, M., et al., "Treatment of the Mangled Lower Extremity After a Terrorist Blast Injury", Clinical Orthopaedics and Related Research, Number 422, pp. 88−96 (May 2004). NPL−251
【非特許文献501】 PARK, G.B., et al., "The Design and Evaluation of a Burn Wound Covering", Supplied by The British Library −"The Words Knowledge", pp. 11−15 (1978). NPL−327
【非特許文献502】 ACU−derm(r) Transparent Moisture Vapor Permeable Polyurethane Dressing, pp. 1−13 and cover sheet. NPL003
【非特許文献503】 3M loban 2, Breathability, Conformability and Strength, Breathability − Moisture Vapor Transmission Rate and Conformability and Strength − Tensile Strength, Elongation and Fn Modulus Test (1 page). NPL−001
【非特許文献504】 SVEDMAN, P., "A dressing allowing continuous treatment of a biosurface," IRCS Medical Science: Biomedical Technology; Clinical Medicine; Surgery and Transplantation, 7:221 (1979). (Exhibit D−407). NPL−387
【非特許文献505】 DAVYDOV, Y., et al., "Bacteriological and Cytological Assessment of Vacuum Therapy of Purulent Wounds," Vestn. Khir., 48−52, English translation by IRC, (Oct. 1988). (Exhibit D−290). NPL−616
【非特許文献506】 DAVYDOV, Y., et al., "Vacuum Therapy in the Treatment of Purulent Lactation Mastitis," Vestn. Khir. P. 66−70, English translation by IRC, (Sept. 1986), (Exhibit D−292). NPL−617
【非特許文献507】 MEYER, W., et al., "Biers Hyperemic Treatment," W.B. Saunders & Co., 1908 (Exhibit D246) NPL−283
【非特許文献508】 Chariker/Jeter/Tintle Slides "Closed Wound Suction" by Dr. Mark Chariker et al., 41 sheets, pages 1−10, 19, 55−84 (0−041) (allegedly dated 1985 and 1986) NPL−079
【非特許文献509】 Jeter, K., list of publications, 4 sheets, (D−161) NPL−225
【非特許文献510】 ALEXANDER, J.W., et al., "Clinical evaluation of epigard, a new synthetic substitute for homograft and heterograft skin," J. of Trauma, 13:374−383, (1973) NPL−010
【非特許文献511】 Anon., "Standard Test Methods for Water Vapor Transmission of Materials," ASTM, Designation: E 96/E 96M - 05, Published June 2005, 11 sheets, (Exhibit D−184) NPL−017
【非特許文献512】 BYERS, R.M., "Clinical effects of closed suction drainage on wound healing in patients with head and neck cancer," Arch. Otolaryngol., vol. 108:723−6, (November 1982). NPL−066
【非特許文献513】 CESANY, P., "Suction in the Treatment of Torpid Ulcerations," Rozhledy v chirurgii, 48−9, MINCO22894−MINCO22898, cover sheet and pages 406−409 English abstract on page 409 (1 sheet printout from PubMed) (September 1969). NPL−072
【非特許文献514】 CHINN, S.D., "Closed wound suction drainage," J. Foot Surg., vol. 24: 76−81, (Jan−Feb 1985). NPL−083
【非特許文献515】 Email dated January 14, 2002 with attachments, including "Report of Meeting with DG Consulting" dated January 10, 2002, 5 sheets, (Exhibit D−157). NPL−137
【非特許文献516】 WESTABY, S., "Treatment of purulent wounds and fistulae with an adhesive wound irrigation device," Annals of the Royal College of Surgeons, vol. 63: 353−6 (1981). NPL−145
【非特許文献517】 HARTZ, R.R., et al., "Healing of the Perinea! Wound," Arch. Surg., vol. 115, 471−474, (1980), (Exhibit D−395). NPL−196
【非特許文献518】 MIZUNO, K., "Suctioning Sponge," Arch. Opthalmol., vol. 101:294, (Feb. 1983). NPL−294
【非特許文献519】 Morykwas, Laboratory Notebook pages and charts; 38 pages (Exhibit D−46) dated prior to March 1993 WFU−45
【非特許文献520】 Morykwas, Laboratory notebook pages and charts, 16 sheets, (Exhibit D−286) dated prior to March 1993 WFU−46
【非特許文献521】 Morykwas, Laboratory notebook pages and charts, 17 sheets, (Exhibit D−233) dated prior to November 1991 WFU−47
【非特許文献522】 NIKOLOV, A., "Method of treatment of postphlebitic and varicose trophic ulcers on the lower extremities by vacuum [Vacuum treatment method in postphlebitic and varicose trophic ulcers of the lower extremities]," Khirurgiia, pages 368−374, (English abstract on page 371 and 1 sheet printout from PubMed) (1981) NPL−314
【非特許文献523】 SMITH, S.R.G., "Surgical drainage", Br. J. Hosp. Med., 33(6):308−315 (June 1985). NPL−379
【非特許文献524】 SVEDMAN, "A dressing system providing fluid supply and suction drainage used for continuous or intermittent irrigation," Ann. Plast. Surg., vol. 17, 9 pages, (August 1986). NPL−389
【非特許文献525】 SVEDMAN, "Irrigation treatment in split thickness skin grafting of intractable leg ulcers," Scand. J. Plast. Reconstr. Surg., vol. 19:211−213, (1985). NPL−390
【非特許文献526】 Morykwas, Laboratory Notebook pages and charts; (D−46) dated prior to November 1991 WFU−49
【非特許文献527】 Morykwas, Laboratory Notebook pages and charts; (D−286) dated prior to November 1991 WFU−50
【非特許文献528】 SPAHN, J.G., "Soft tissue challenges in the head and neck region,"Clinical Seminar Handout, EHOB, (46 pages) NPL−621
【非特許文献529】 MENDEZ−EASTMAN, S., "Guidelines for using negative pressure wound therapy", Adv. Skin Wound Care, 14 (6):314−323. (16 pp.) (November − December 2001). NPL−278
【非特許文献530】 Addition to the "Users Manual Concerning Overflow Protection−Concerns all Egnell Pumps", dated February 3, 1983, 1 page Swedish, [1 page English]. NPL−680
【非特許文献531】 Aeros, "Moblvac,""introducing the off the wall vacuum system,"Aeros Instruments, Life Support Nursing, 3(1):34−37, Barlin Publishing Ltd. (January − February 1980). NPL−007
【非特許文献532】 Article in Russian, pp. 84−85; NPL−619
【非特許文献533】 AUSTAD, E.D., et al., "Tissue expansion: dividend or loan?"Plast. Reconstr. Surg.,78(1):63−67 (July 1986). NPL−023
【非特許文献534】 BlueSky Medical, 2 sheets of advertisement, "Introducing the Chariker−Jeter wound drainage kit" and "Introducing the Kremlin (r) wound drainage kit" NPL−620
【非特許文献535】 Egnell Minor, Instruction Book, First Addition [Edition], allegedly dated February 1987, 21 pages Swedish, 3 pages English. NPL−681
【非特許文献536】 FEIERABEND, T.C., et al., "Injuries causing major loss of scalp", Plast. Reconstr. Surg., [Abstract only − 1 pp. printout from PubMed], 76(2):189−194 (August 1985). NPL−623
【非特許文献537】 GERONEMUS, R.G., et al., "The effect of two new dressings on epidermal wound healing", J. Dermatol. Surg. Oncol., 8(10):850−852 (October 1982). NPL−606
【非特許文献538】 MILLER, S.H., et al., "An inexpensive wound suction device", Surg. Gyencol. Obstet., 141(5):768 (November 1975). NPL−607
【非特許文献539】 MILLER, S.J., "Surgical wound drainage system using silicone tubing", J. Am. Podiatry Assn., 71(6): pp. 287−296, (June 1981). NPL−605
【非特許文献540】 NELSON, R.P., et al., "Use of negative pressure suction in urology", Urology, 4(5):574−576, (November 1974). NPL−494
【非特許文献541】 SVEDMAN, "Irrigation Treatment of Leg Ulcers", The Lancet, September 3, 1983, pp. 532−534. NPL−679
【非特許文献542】 STEWART, A., et al., "Cleaning v. healing," Community Outlook, pp. 22, 24 & 26 (August 14, 1985). NPL−601
【非特許文献543】 TRAMMELL, T.R., et al., "Closed−wound drainage systems: the Solcotrans Plus versus the Stryker−CBC ConstaVAC", Orthopaedic Review, 20(6):536−542 (June 1991). NPL−608
【非特許文献544】 VVOODLEY, D.T., et al., "A double−blind comparison of adhesive bandages with the use of uniform suction blister wounds", Arch. Dermatol., 128(10):1354, 1357 (October 1992). NPL−609
【非特許文献545】 ZELKO, J.R., et al., "Primary closure of the contaminated wound; closed suction wound catheter", Am. J. Surgery, 142:704−706, (December 1981). NPL−604
【非特許文献546】 THOMAS, S., "Wound management and dressings," cover sheet, preface, sheet labeled "Chapter 5" and pp. 36−39 (1990). MolnlyckeDEVVH1−003
【非特許文献547】 "Pressure equivalents," McGraw−Hill Encyclopedia of Science & Technology, 6th ed., New York, pp. 249, (1987).NPL−687bw
【非特許文献548】 BAGAUTDINOV, N.A., "Alternative method of external vacuum aspiration in the treatment of purulent soft tissue disease," Curr. Problems Contemporary Clin. Surg.: Interscholastic Collection, pp. 94−96, (6 sheets of English translation and certification dated May 30, 2008; four sheets of English translation, 6 sheets in Russian, and certification dated May 9, 2008; 1 sheet of English translation of alleged library index card, 1 sheet in Russian, and certification dated May, 7, 2008); I.N. Ulianov Chuvash State University, Cheboksary, (1986). NPL−690
【非特許文献549】 ZIVADINOVIC, G., et al., "Vacuum therapy in the treatment of peripheral blood vessels," Conference Papers of the 5th Timok Medical Days, Majdanpek, No. 3−4, pp. 161−164, (5 sheets English translation; 5 sheets in Serbian, certification dated May 9, 2008) (1986). NPL−691
【非特許文献550】 JOHNSON, F.E., "An improved technique for skin graft placement using a suction drain", Surg. Gynecol. Obstet., 159 (6):584−585 (December 1984). NPL−226_
【非特許文献551】 SAFRONOV, A.A., Dissertation Abstract, "Vacuum therapy of trophic ulcers of the lower leg with simultaneous
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【非特許文献552】 TRIBBLE, D.E., "An improved sump drain−irrigation device of simple construction," Arch. Surg., 105:511−513, (Sep. 1972). NPL−693
【非特許文献553】 TENNANT, C.E., "The use of hyperemia in the postoperative treatment of lesions of the extremities and thorax," Jour. A.M.A., 64(19):1548−1549, (May 8, 1915). NPL−694
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【非特許文献555】 "V.A.C.(r) Therapy Clinical Guidelines: A reference source for clinicians," KCI, The Clinical Advantage (r) (July 2007). NPL−696
【非特許文献556】 BAGAUTDINOV, N.A., "Variant of external vacuum aspiration in the treatment of purulent diseases of soft tissues," Current Problems in Modern Clinical Surgery, Interdepartmental Collection, Cheboksary, (4 pages of English translation, 6 sheets in Russian, certification dated May 22, 2008, English translation of index card, 1 sheet Russian, certification dated May 7, 2008) (1986). NPL−697
【非特許文献557】 CHARDAK, W.M., et al., "Experimental studies on synthetic substitutes for skin and their use in the treatment of burns," Ann. Surg., 155(1):127−139, (Jan. 1962). NPL−698
【非特許文献558】 FUJIMORI, R., et al., "Sponge fixation method for treatment of early scars," Plast. & Reconst. Surg., 42(4):322−326, (Oct. 1968). NPL−699
【非特許文献559】 KIRK−OTHMER, Encyclopedia of Chemical Technology, 2nd completely revised edition, vol. 14, pp. 227, John Wiley & Sons, Inc., (1967). NPL−700
【非特許文献560】 MEYER, W., et al., excerpts from "Biers Hyperemic Treatment", W.B. Saunders and Co., (47 sheets) (1908). NPL−702
【非特許文献561】 ZIVADINOVIC, G., et al., "Vacuum therapy in the treatment of peripheral blood vessels," Timok Medical Journal, Abstract book of the 5th Timok Medical Days, Majdanpek, 6 sheets of English translation, (1986). NPL−703
【非特許文献562】 SAFRONOV, A.A., "Vacuum therapy for trophic ulcers of the tibia with concurrent skin autoplasty," Dissertation abstract, additional abstract, Moscow, 20 sheets of English translation, (1967). NPL−704
【非特許文献563】 SAFRONOV, A.A., Abstract of Invention No. 240188, "Device for wound or ulcer treatment," (2 sheets English translation and 2 sheets in Russian) (1969). NPL−705
【非特許文献564】 CONQUEST, A.M., et al., "Hemodynamic effects of the vacuum−assisted closure device on open mediastinal wounds,"J. Surg. Res., 115(2):209−13 (December 2003). NPL−093
【非特許文献565】 COPSON, D., "Topical negative pressure and necrotising fasciitis", Nurs. Stand., 18(6):71−2, 74, 76, 78, 80 (October 22, 2003). NPL−100
【非特許文献566】 DEMARIA, R.G., et al., "Topical negative pressure therapy. A very useful new method to treat severe infected vascular approaches in the groin,"J. Cardiovascular Surg., 44(6):757−61 (December 2003). NPL−112
【非特許文献567】 DE VOOGHT, A., et al., "Vacuum−assisted closure for abdominal wound dehiscence with prosthesis exposure in hernia surgery,"Plast. Recontr. Surg., 112(4):1188−9 (September 15, 2003). NPL−115
【非特許文献568】 DUXBURY, M.S., et al., "Use of a vacuum assisted closure device in pilonidal disease,"J. Wound Care, 12(9):355 (October 2003). NPL−127
【非特許文献569】 ELDAD, A., et al., Vacuum−− A novel method for treating chronic wounds", Harefuah, (English abstract on last 2 pp. and 1 sheet printout from PubMed); 142(12):834−6, 878, 877 (December 2003). NPL−135
【非特許文献570】 EVANS, D., et al., "Topical negative pressure for treating chronic wounds", Cochrane Database Syst. Rev., vol. (3), accession no. 00075320−100000000−01309 (2005). NPL−143
【非特許文献571】 FUCHS, U., et al., "Clinical outcome of patients with deep sternal wound infection managed by vacuum−assisted closure compared to conventional therapy with open packaging: a retrospective analysis", Ann. Thorac. Surg., 79:526−31 (2005). NPL−168
【非特許文献572】 GUSTAFSSON, R.I., et al., "Deep sternal wound infection: a sternal−sparing technique with vacuum−assisted closure therapy"Ann. Thorac. Surg., 76(6):2048−53 (December 2003). NPL−182
【非特許文献573】 HERSCOVICI Jr., D., et al., "Vacuum−assisted wound closure (VAC therapy) for the management of patients with high−energy soft tissue injuries", J. Orthop. Trauma, 17(10):683−8 (November − December 2003). NPL−201
【非特許文献574】 HUANG, J., et al., "Treatment of open fracture by vacuum sealing technique and internal fixation", Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, (English abstract on first page and 2 sheets printout from PubMed); 17(6):456−8 (November 2003). NPL−213
【非特許文献575】 JONES, E.G., et al., "Management of an ileostomy and mucous fistula located in a dehisced wound in a patient with morbid obesity", J. Wound Ostomy Continence Nurs., 30(6):351−356 (November 2003). NPL−227
【非特許文献576】 LANGLEY−HAWTHORNE, C., "Economics of negative pressure wound therapy", Ostomy Wound Manage., 50(4A suppl):35, 36, C3 (April 2004). NPL−250
【非特許文献577】 NEUBAUER, G., et al., "The cost−effectiveness of topical negative pressure versus other wound−healing therapies", J. Wound Care, 12(10):392−3 (November 2003). NPL−312
【非特許文献578】 ORGILL, D.P., et al., "Functional reconstruction following electrical injury", Ann. N.Y. Acad. Sci., 888:96−104 (October 30, 1999). NPL−321
【非特許文献579】 SALAMEH, J.R., et al., "Laparoscopic harvest of omental flaps for reconstruction of complex mediastinal wounds", JSLS, 7(4):317−22 (October − December 2003). NPL−352
【非特許文献580】 SHOUFANI, A., et al., "Vacuum assisted closure- a new method for wound control and treatment", Harefuah, (English abstract on last page; 1 sheet printout from PubMed); 142(12):837−40, 877 (December 2003). NPL−367
【非特許文献581】 SHVARTSMAN, H.S., et al., "Use of vacuum−assisted closure device in the treatment of recurrent Pagets disease of the vulva", Obstet. Gynecol., Supplement, 102(5, part 2):1163−6 (November 2003). NPL−368
【非特許文献582】 SIBBALD, R.G., et al., "A consensus report on the use of vacuum−assisted closure in chronic, difficult−to−heal wounds", Ostomy Wound Manage., 49(11):52−66 (November 2003). NPL−369
【非特許文献583】 WAGNER, S., et al., "Comparison of inflammatory and systemic sources of growth factors in acute and chronic human wounds", Wound Rep. Reg., 11:253−260 (July − August 2003). NPL−426
【非特許文献584】 WILD, T., "Consensus of the German and Austrian Societies for wound healing and wound management on vacuum closure and the VAC treatment unit", MMW Fortschr. Med., (English abstract on page 100; 1 sheet printout from PubMed); 145 Suppl. 3:97−101 (October 9, 2003). NPL−435
【非特許文献585】 CHEN, S.Z., et al., "Effect of vacuum−assisted closure on the expression of proto−oncogenes and its significance during wound healing", Zhonghua Zheng Xing Wai Ke Za Zhi, (English abstract on first page, 2 sheets printout from PubMed); 21:197−200 (May 2005). NPL−456
【非特許文献586】 IMMER, F.F., et al., "Deep sternal wound infection after cardiac surgery: modality of treatment and outcome", Ann. Thorac. Surg., 80(3):957−61 (September 2005; available online August 23, 2005). NPL−457
【非特許文献587】 SALTZMAN, C.L., "Salvage of diffuse ankle osteomyelitis by single−stage resection and circumferential frame compression arthrodesis", Iowa Orthop. J., 25:47−52 (2005). NPL−458
【非特許文献588】 BOGART, L., "A summary of posters presented at the symposium on Advanced Wound Care: 2003 and 2004", ry
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【非特許文献589】 CHEN, S.Z., et al., "Effects of vacuum−assisted closure on wound microcirculation: an experimental study", Asian J. Surg., 28(3):211−7 (July 2005). NPL−460
【非特許文献590】 PAUL, J.C., "Vacuum assisted closure therapy: A must in plastic surgery", Plastic Surg. Nurs., 25(2):61−5 (April − June 2005). NPL−462
【非特許文献591】 WINTER, D., "Perspectives on vacuum−assisted closure therapy in pilonidal sinus surgery", Dis. Colon Rectum, 48 (9):1829−30, (September 2005). NPL−463
【非特許文献592】 ARCA, M.J., et al., "Use of vacuum−assisted closure system in the management of complex wounds in the neonate", Pediatr. Surg. Int., 21(7):532−5, 8 sheets, (published online June 17, 2005). NPL−464
【非特許文献593】 ADAMKOVA, M., et al., "First experience with the use of vacuum assisted closure in the treatment of skin defects at the bum center", Acta. Chir. Plast., 47(1):24−7 (2005). NPL−465
【非特許文献594】 VENTURI, M.L., et al., "Mechanisms and clinical applications of the vacuum−assisted closure (VAC) device: a review", Am. J. Clin. Dermatol., 6(3):185−94 (2005). NPL−466
【非特許文献595】 NOEL, B., "Management of venous leg ulcers", Rev. Med. Suisse, (English abstract on first page, 1 sheet printout from PubMed); 1(16):1062−6, 1068 (April 20, 2005). NPL−467
【非特許文献596】 RICCIO, M., et al., "Delayed microsurgical reconstruction of the extremities for complex soft−tissue injuries", Microsurgery, 25:272−83 (2005). NPL−468
【非特許文献597】 SJOGREN, J., et al., "Clinical outcome after poststernotomy mediastinitis: vacuum−assisted closure versus conventional treatment", Ann. Thorac. Surg., 79(6):2049−55 (June 2005). NPL−469
【非特許文献598】 DAINTY, L.A., et al., "Novel techniques to improve split−thickness skin graft viability during vulvo−vaginal reconstruction", Gynecol. Oncol., 97(3):949−52 (June 2005). NPL−470
【非特許文献599】 CLUBLEY, L., et al., "Using negative pressure therapy for healing of a sternal wound", Nurs. Times, 101(16):44−6 (April 19, 2005). NPL−471
【非特許文献600】 CANIANO, D.A., et al., "Wound management with vacuum−assisted closure: experience in 51 pediatric patients", J. Pediatr. Surg., 40(1):128−32 (January 2005). NPL−472
【非特許文献601】 STEENVOORDE, P., et al., "Deep infection after ilioinguinal node dissection: vacuum−assisted closure therapy?"Low. Extrem. Wounds, 3(4):223−226 (December 2004). NPL−473
【非特許文献602】 RYAN, T.J., "Evans (1966) exchange and the skin in the light of vacuum−assisted dosure, yoga, and maggots", Low. Extrem. Wounds, 3(3):121−2 (September 2004). NPL−474
【非特許文献603】 ARMSTRONG, D.G., et al., "Decreasing foot pressures while implementing topical negative pressure (vacuum−assisted closure) therapy", Low. Extrem. Wounds, 3(1):12−15 (March 2004). NPL−475
【非特許文献604】 WACKENFORS, A., et al., "Blood flow responses in the peristernal thoracic wall during vacuum−assisted closure therapy", Ann. Thorac. Surg., 79(5):1724−31 (May 2005). NPL−476
【非特許文献605】 OCONNOR, J., et al., "Vacuum−assisted closure for the treatment of complex chest wounds", Ann. Thorac. Surg., 79 (4):1196−200 (April 2005). NPL−478
【非特許文献606】 NUGENT, N., et al., "Vacuum−assisted closure − A management option for the burns patients with exposed bone", Burns, 31(3):390−393 (May 2005) (Epub January 22, 2005). NPL−479
【非特許文献607】 LAMBERT, K.V., et al., "Vacuum assisted closure: a review of development and current applications", Eur. J. Vasc. Endovasc. Surg., 29(3):219−226 (March 2005). NPL−480
【非特許文献608】 SMITH, N., "The benefits of VAC Therapy in the management of pressure ulcers", Br. J. Nurs., 13(22):1359−60, 1362, 1364−65 (December 9, 2004 − January 12, 2005). NPL−481
【非特許文献609】 WHITE, R.A., et al., "Vacuum−assisted closure complicated by erosion and hemorrhage of the anterior tibial artery", J. Orthop. Trauma, 19(1):56−59 (January 2005). NPL−482
【非特許文献610】 DE GEUS, H.R.H., et al., "Vacuum−assisted closure in the treatment of large skin defects due to necrotizing fasciitis", Intensive Care Med., 31(4): 601 (1 page) (April 2005) (Epub January 22, 2005). NPL−483
【非特許文献611】 SAMSON, D., et al., "Wound−healing technologies: low level laser and vacuum−assisted closure", Evid. Rep. Technol. Assess. (Summ.),(111):1−6, (December 2004). NPL−484
【非特許文献612】 GIBSON, K., "Vacuum−assisted closure", Am. J. Nurs., 104(12):16 (1 page) (December 2004). NPL−485
【非特許文献613】 POLLY JR., D.W., et al., "Advanced medical care for soldiers injured in Iraq and Afghanistan", Minn. Med., 87(11):42−4 (November 2004). NPL−486
【非特許文献614】 STONE, P.A., et al., "Vacuum−assisted fascia! closure for patients with abdominal trauma", J. Trauma, 57:1082−6 (November 2004). NPL−487
【非特許文献615】 CONNOLLY, T.P., "Necrotizing surgical site infection after tension−free vaginal tape", Obstet. Gynecol., 104(6):1275−6 (4 pages) (December 2004). NPL−488
【非特許文献616】 WACKENFORS, A., et al., "Effects of vacuum−assisted closure therapy on inguinal wound edge microvascular blood flow", Wound Rep. Regen., 12(6):600−6 (November − December 2004). NPL−489
【非特許文献617】 SCHAFFZIN, D.M., et al., "Vacuum−assisted closure of complex perinea! wounds", Dis. Colon Rectum, 47:1745−8 (October 2004) (Published online August 24, 2004). NPL−490
【非特許文献618】 YOUSAF, M., et al., "Use of vacuum−assisted closure for healing of a persistent perineal sinus following panproctocolectomy: report of a case", Dis. Colon Rectum, 47(8):1403−8 (August 2004) (Published online August 12, 2004). NPL−491
【非特許文献619】 FOX, A., et al., "An unusual complication of vacuum assisted closure in the treatment of a pressure ulcer", J. Wound Care, 13(8):344−5 (September 2004). NPL−492
【非特許文献620】 SAXENA, V., et al., "Vacuum−assisted closure: microdeformations of wounds and cell proliferation", Plast. Reconstruct. Surg., 114(5):1086−96 (October 2004). NPL−493
【非特許文献621】 SCHOLL, L., et al., "Sternal osteomyelitis: use of vacuum−assisted closure device as an adjunct to definitive closure with stemectomy and muscle flap reconstruction", J. Card. Surg., 19(5):453−61 (September − October 2004). NPL−495
【非特許文献622】 OHYE, R.G., et al. "Primary closure for postoperative mediastinitis in children", J. Thorac. Cardiovasc. Surg., 128 (3):480−6 (September 2004). NPL−496
【非特許文献623】 TANG, S.Y., et al., "Influence of vacuum−assisted closure technique on expression of BcI−2 and NGF/NGFmRNA during wound healing", Zhonghua Zheng Xing Wai Ke Za Zhi, (English abstract on first page 1 sheet printout from PubMed); 20(2):139−42 (March 2004). NPL−497
【非特許文献624】 ARMSTRONG, D.G., et al., "Guidelines regarding negative wound therapy (NPWT) in the diabetic foot", Ostomy Wound Manage., 50(4B Suppl.):3S−27S (April 2004). NPL−498
【非特許文献625】 SHILT, J.S., et al., "Role of vacuum−assisted closure in the treatment of pediatric lawnmower injuries", J. Pediatr. Orthop., 24(5):482−7 (September − October 2004). NPL−499
【非特許文献626】 ANTONY, S., et al., "A retrospective study: clinical experience using vacuum−assisted closure in the treatment of wounds", J. Natl. Med. Assoc., 96(8):1073−7 (August 2004). NPL−500
【非特許文献627】 STEENVOORDE, P., et al., "Vacuum−assisted closure therapy and oral anticoagulation therapy", Plast. Reconstruct. Surg., 113(7):2220−1 (June 2004). NPL−501
【非特許文献628】 OCZENSKI, W., et al., "Vacuum−assisted closure for the treatment of cervical and mediastinal necrotizing fasciitis", J. Cardiothorac. Vasc. Anesth., 18(3):336−8 (June 2004). NPL−502
【非特許文献629】 CARSON, S.N., et al., "Vacuum−assisted closure used for healing chronic wounds and skin grafts in the lower extremities", Ostomy Wound Manage., 50(3):52−8 (9 sheets) (March 2004). NPL−503
【非特許文献630】 MARATHE, U.S., et al., "Use of the vacuum−assisted closure device in enhancing closure of a massive skull defect", Laryngoscope, 114(6):961−4 (8 sheets) (June 2004). NPL−504
【非特許文献631】 SCHINTLER, M.V., et al., "The impact of the VAC−treatment for locally advanced malignancy of the scalp", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl: 1:S141−S146 (May 2004). NPL−505
【非特許文献632】 QUERINGS, K., et al., "Revitalization of a gluteal abscesses with V.A.C. therapy (vacuum assisted dosure)", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1:S138−S140 (May 2004). NPL−506
【非特許文献633】 KALL, S., et al., "Influence of foam− and tubing material of the vacuum assisted closure device (V.A.C.) on the concentration of transforming growth factor beta 1 in wound fluid", Zentralbl. Chir., (English abstract on first page, 2 sheets printout from PubMed); 129 Suppl 1: S113−S115 (May 2004). NPL−507
【非特許文献634】 MANG, R., et al., "Vacuum therapy in a pre− and postsurgical ulcera crurum", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1:S101−S103 (May 2004). NPL−508
【非特許文献635】 STEIERT, A.E., et al., "The V.A.C. system (vacuum assisted closure) as bridging between primary osteosynthesis in conjunction with functional reconstructed of soft tissue − open fractures type 2 and type 3", Zentralbl. Chir., (English abstract on first page, 2 sheets printout from PubMed); 129 Suppl 1:S98−100 (May 2004). NPL−509
【非特許文献636】 KARL, T., et al., "Indications and results of V.A.C. therapy treatments in vascular surgery − state of the art in the treatment of chronic wounds", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1:S74−S79 (May 2004). NPL−510
【非特許文献637】 FERBERT, T., et al., "Treatment of soft tissue defects on hand and forearm with vacuum assisted closure", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1:S57−S58 (May 2004). NPL−511
【非特許文献638】 HALAMA, D., et al., "Intraoral application of vacuum−assisted closure in the treatment of an extended mandibular keratocyst", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1:S53−S56 (May 2004). NPL−512
【非特許文献639】 FLECK, T., et al., "Early treatment of sternal wound infections with vacuum assisted closure therapy reduces involvement of the mediastinum and further diminishes the need of plastic reconstructive surgery", Zentralbl. Chir., (1 sheet printout from PubMed); 129 Suppl 1:S35−S37 (May 2004). NPL−513
【非特許文献640】 KUTSCHKA, I., et al., "Vacuum assisted closure therapy improves early postoperative lung function in patients with large sternal wounds", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1: S33−S34 (May 2004). NPL−514
【非特許文献641】 LABLER, L., et al., "New application of V.A.C. (vacuum assisted closure) in the abdominal cavity in case of open abdomen therapy", Zentralbl. Chir., (English abstract on first page, 2 sheets printout from PubMed); 129 Suppl 1:S14− S19 (May 2004). NPL−515
【非特許文献642】 WILD, T., et al., "Consensus of the German and Austrian Societies for Wound Healing and Wound Management on vacuum closure and the V.A.C. treatment unit", Zentralbl. Chir., (English abstract on first page, 2 sheet printout from PubMed and 1 sheet of erratum); 129 Suppl 1:S7−S11 (May 2004). NPL−516
【非特許文献643】 WEED, T., et al., "Quantifying bacterial bioburden during negative pressure wound therapy. Does the wound VAC enhance bacterial dearance?"Ann. Plast. Surg., 52(3):276−80 (March 2004). NPL−517
【非特許文献644】 MUSTOE, T., "Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy", Am. J. Surg., 187(5A):65S−70S (May 2004). NPL−518
【非特許文献645】 TZENG, Y.J., et al., "Using vacuum−assisted closure (VAC) in wound management", Hu Li Za Zhi, (English abstract on last page, 1 sheet printout from PubMed); 51(2):79−83 (April 2004). NPL−519
【非特許文献646】 QUAH, H.M., et al., "Vacuum−assisted dosure in the management of the open abdomen: a report of a case and initial experiences", J. Tissue Viability, 14(2):59−62 (April 2004). NPL−521
【非特許文献647】 EMOHARE, 0., et al., "Vacuum−assisted closure use in calciphylaxis", J. Burn Care Rehabil., 25(2):161−4 (March − April 2004). NPL−522
【非特許文献648】 WACKENFORS, A., et al., "The effect of vacuum−assisted closure therapy on the pig femoral artery vasomotor responses", Wound Repair Regen., 12(2):244−51 (March − April 2004). NPL−523
【非特許文献649】 SJOGREN, J., et al., "Vacuum−assisted closure therapy in mediastinitis after heart transplantation", J. Heart Lung Transplant., 23(4):506−7 (April 2004). NPL−524
【非特許文献650】 MILLER, Q., et al., "Effect of subatmospheric pressure on the acute healing wound", Curr. Surg., 61(2):205−8 (March − April 2004). NPL−525
【非特許文献651】 PENN, E., et al., "Management of a dehisced abdominal wound with VAC therapy", Br. J. Nurs., 13(4):194, 196, 198−201 (February 26 − March 10, 2004). NPL−526
【非特許文献652】 MOUES, C.M., et al., "Bacterial load in relation to vacuum−assisted closure wound therapy: a prospective randomized trial", Wound Repair Regen., 12(1):11−7 (January − February 2004). NPL−527
【非特許文献653】 SCHIMP, V.L., et al., "Vacuum−assisted dosure in the treatment of gynecologic oncology wound failures", Gynecol. Oncol., 92(2):586−91 (February 2004). NPL−528
【非特許文献654】 ARU, G.M., et al., "Limitations on the role of vacuum−assisted closure in cardiac surgery", J. Thorac. Cardiovasc. Surg., 127(2):604−5 (February 2004). NPL−529
【非特許文献655】 BIHARIESINGH, V.J., et al., "Plastic solutions for orthopaedic problems", Arch. Orthop. Trauma. Surg., 124(2):73−6 (March 2004) (Epub January 17, 2004). NPL−530
【非特許文献656】 KAPLAN, M., "Managing the open abdomen", Ostomy Wound Manage., 50(1A suppl):C2, 1−8, and 1 sheet of quiz (January 2004). NPL−531
【非特許文献657】 COLWELL, A.S., et al., "Management of early groin vascular bypass graft infections with sartorius and rectus femoris flaps", Ann. Plast. Surg., 52(1):49−53 (January 2004). NPL−532
【非特許文献658】 Evidence Report/Technology Assessment, No. 111, "Wound healing technologies: low−level laser and vacuum−assisted closure", prepared for Agency for Healthcare Research and Quality by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence−based Practice Center, under Contract No. 290−02−0026, AHRQ Publications Clearinghouse, Available December 2004. NPL−533
【非特許文献659】 WOLVOS, T., "Wound instillation- the next step in negative pressure wound therapy. Lessons learned from initial experiences", Ostomy Wound Manage., 50(11):56−58, 60−66 (November 2004). NPL−534
【非特許文献660】 BLUMAN, E.M., et al., "Subatmospheric pressure−induced compartment syndrome of the entire upper extremity. A case report", J. Bone Joint Surg. (Am.), 86−A(9):2041−4 (September 2004). NPL−535
【非特許文献661】 KAMOLZ, L.P., et al., "Use of subatmospheric pressure therapy to prevent burn wound progression in human: first experiences", Burns, 30(3):253−8 (May 2004) (Available online March 16, 2004). NPL−536
【非特許文献662】 JONES, S.M., et al., "Advances in wound healing: topical negative pressure therapy", Postgrad. Med. J., 81 (956):353−7 (June 2005). NPL−537
【非特許文献663】 MOUES, C.M., et al., "An economic evaluation of the use of TNP on full−thickness wounds", J. Wound Care, 14 (5):224−7 (May 2005). NPL−538
【非特許文献664】 LEE, S.S., et al., "Management of intractable sternal wound infections with topical negative pressure dressing", J. Card. Surg., 20(3):218−22 (May − June 2005). NPL−539
【非特許文献665】 JETHWA, P., et al., "Using topical negative pressure therapy to resolve wound failure following perinea! resection", J. Wound Care, 14(4):166−7 (April 2005). NPL−540
【非特許文献666】 BANWELL, P.E., et al., "Topical negative pressure therapy: mechanisms and indications", Int. Wound J., 1(2):95 (15 pages) (June 2004). NPL−541
【非特許文献667】 MELANO, E., et al., "The effects of Panafil when using topical negative pressure to heal an infected sternal wound,"J. Wound Care, 13(10):425−6 (November 2004). NPL−542
【非特許文献668】 MORTON, N., "Use of topical negative pressure therapy in postoperative dehisced or infected wounds", J. Wound Care, 13(8):346−8 (September 2004). NPL−543
【非特許文献669】 MOISIDIS, E., et al., "A prospective, blinded, randomized, controlled clinical trial of topical negative pressure use in skin grafting", Plast. Reconstr. Surg., 114(4):917−22 (7 sheets) (September 15, 2004). NPL−544
【非特許文献670】 TACHI, M., et al., "Topical negative pressure using a drainage pouch without foam dressing for the treatment of undetermined pressure ulcers", Ann. Plast. Surg., 53(4):338−42 (7 sheets) (October 2004). NPL−545
【非特許文献671】 JONES, S.M., et al., "Complications of topical negative pressure therapy in small−diameter wounds", Plast. Reconstr. Surg., 114(3):815−817 (5 sheets) (September 1, 2004). NPL−546
【非特許文献672】 LOREE, S., et al., "Is vacuum assisted closure a valid technique for debriding chronic leg ulcers?"J. Wound Care, 13 (6):249−52 (June 2004). NPL−547
【非特許文献673】 VOGT, P.M., et al., "Several aspects of foam materials and their possible interactions with the wound surface in the vacuum therapy", Zentralbl. Chir., (English abstract on first page, 1 sheet printout from PubMed); 129 Suppl 1:S92−S94 (May 2004). NPL−548
【非特許文献674】 HASLIK, W., et al., "The use of subatmospheric pressure to prevent burn wound progression: first experiences in bum wound treatment", Zentralbl. Chir., (English abstract on first page, and 1 sheet printout from PubMed); 129 Suppl. 1: S62−63 (May 2004). NPL−549
【非特許文献675】 STEENVOORDE, P., et al., "Combining topical negative pressure and a Bogota bag for managing a difficult laparostomy", J. Wound Care, 13(4):142−3 (April 2004). NPL−550
【非特許文献676】 PULLEN, R., "Treatment of pressure sores in elderly patients", Z. Genrontol. Geriatr., (English abstract on first page, 1 sheet printout from PubMed); 37(2):92−9 (April 2004). NPL−551
【非特許文献677】 GOTTRUP, F., "Optimizing wound treatment through health care structuring and professional education", Wound Repair Regen., 12(2):129−33 (March − April 2004). NPL−552
【非特許文献678】 (Anon.) "New best practice guidelines for managing pressure ulcers with negative pressure wound therapy published", Home Healthcare Nurse, 23(7):469 (one sheet) (July 2005). NPL−553
【非特許文献679】 STECHMILLER, J.K., et al., "Effect of negative pressure wound therapy on the expression of TNF−alpha, IL−1beta, MMP−2, MMP−3, and TIMP−1 in wound fluids of adults with pressure ulcers", Wound Repair Regen., 13(2):A16 (March − April 2005). NPL−554
【非特許文献680】 SNYDER, R.J., "Negative pressure wound therapy (NPWT)/ vacuum−assisted closure(r) (VAC(r)) as an adjunct in the treatment of pyoderma gangrenosum", Wound repair and regeneration, 13:A29 (March 2005). NPL−555
【非特許文献681】 ARMSTRONG, D.G., et al., "Negative pressure wound therapy in treatment of diabetic foot wounds: a marriage of modalities", Ostomy Wound Manage., 50(4A suppl):9−12 (April 2004). NPL−556
【非特許文献682】 ARMSTRONG, D.G., et al., "Plantar pressure changes using novel negative pressure wound therapy technique", J. Am. Podiatr. Med. Assoc., 94(5):456−60 (September − October 2004). NPL−557
【非特許文献683】 BAHARESTANI, M.M., "Negative pressure wound therapy: An examination of cost−effectiveness", Ostomy Wound Manage., 50(11A suppl):29S−33S (November 2004). NPL−558
【非特許文献684】 BERNSTEIN, B.H., et al., "Combination of subatmospheric pressure dressing and gravity feed antibiotic instillation in the treatment of post−surgical diabetic foot wounds: a case series,"parts 1 and 2, Wounds, 17(2):37−48 (23 sheets) (February 2005). NPL−559
【非特許文献685】 DATIASHVILI, R.O., et al., "Negative pressure dressings: An alternative to free tissue transfers?"Wounds, 17 (8):206−212 (August 2005). NPL−560
【非特許文献686】 DE LEON, J., "Negative pressure wound therapy in pressure ulcer management", Ostomy Wound Manage., 51(2A suppl):3S−8S (February 2005). NPL−561
【非特許文献687】 DOBKE, M.K., et al., "A novel approach to acute infection of the glenohumeral joint following rotator cuff repair − a case series", Wounds, 17(6):137−40 (6 sheets) (June 2005). NPL−562
【非特許文献688】 DUNBAR, A., et al., "Addressing the pain: Silicone net dressings as an adjunct with negative pressure wound therapy", Ostomy Wound Manage., 51(4):18−20 (4 sheets) (April 2005). NPL−563
【非特許文献689】 ETOZ, A., et al., "The use of negative pressure wound therapy on diabetic foot ulcers: A preliminary controlled trial", Wounds, 16(8):264−9 (August 2004). NPL−564
【非特許文献690】 FIFE, C.E., et al, "Healing dehisced surgical wounds with negative pressure wound therapy", Ostomy Wound Manage., 50(4A suppl):28−31 (April 2004). NPL−565
【非特許文献691】 GELLER, S.M., et al., "Ulceration of pyoderma gangrenosum treated with negative pressure wound therapy", J. Am. Podiatr. Med. Assoc., 95(2):171−4 (March − April 2005). NPL−566
【非特許文献692】 GRAY, M., et al., "Is negative pressure wound therapy effective for the management of chronic wounds?"J. Wound Ostomy Continence Nurs., 31(3):101−5 (May − June 2004). NPL−567
【非特許文献693】 GUPTA, S., et al., "A literature review of negative pressure wound therapy", Ostomy Wound Manage., 50(11A suppl):2S−4S (November 2004). NPL−568
【非特許文献694】 GUPTA, S., et al., The perioperative use of negative pressure wound therapy in skin grafting", Ostomy Wound Mangage., 50(4A suppl):32−4 (April 2004). NPL−569
【非特許文献695】 GUPTA, S., et al., "Guidelines for managing pressure ulcers with negative pressure wound therapy", Adv. Skin Wound Care, 17(Suppl 2):1−16 (November − December 2004). NPL−570
【非特許文献696】 HULJEV, D., et al., "Necrotizing fasciitis of the abdominal wall as a post−surgical complication: a case report", Wounds, 17(7):169−77 (10 sheets) (2005) (Posted August 11, 2005). NPL−571
【非特許文献697】 KAPLAN, M., "Negative pressure wound therapy in the management of abdominal compartment syndrome", Ostomy Wound Manage., 51(2A suppl):29S−35S (February 2005). NPL−572
【非特許文献698】 MENDEZ−EASTMAN, S., "Determining the appropriateness of negative pressure wound therapy for pressure ulcers", Ostomy Wound Manage., 50(4A suppl):13−16 (April 2004). NPL−573
【非特許文献699】 MENDEZ−EASTMAN, S., "Using negative−pressure for positive results", Nursing, 35(5):48−50 (May 2005). NPL−574
【非特許文献700】 MILLER, M.S., et al., "Negative pressure wound therapy: a rose by any other name", Ostomy Wound Manage., 51 (3):44−9 (11 sheets) (March 2005). NPL−575
【非特許文献701】 NIEZGODA, J.A., et al., "The economic value of negative pressure wound therapy", Ostomy Wound Manage., 51 (2A suppl):44S−47S (February 2005). NPL−576
【非特許文献702】 NIEZGODA, J.A., "Combining negative pressure wound therapy with other wound management modalities", Ostomy Wound Manage., 51(2A suppl):S36−8 (February 2005). NPL−577
【非特許文献703】 ORGILL, D.P., et al., "Guidelines for treatment of complex chest wounds with negative pressure wound therapy", Supplement B to Wounds: A Compendium of Clinical Research and Practice, (24 sheets) (December 2004). NPL−578
【非特許文献704】 ORGILL, D.P., "Utilizing negative pressure wound therapy on open chest/sternotomy wounds", Ostomy Wound Manage., 50(11A suppl):15S−17S (November 2004). NPL−579
【非特許文献705】 ORGILL, D.P., "Advancing the treatment options of chest wounds with negative pressure wound therapy", Ostomy Wound Manage., 51(2A suppl):39S−43S (February 2005). NPL−580
【非特許文献706】 PAGE, J.C., et al., "Retrospective analysis of negative pressure wound therapy in open foot wounds with significant soft tissue defects", Adv. Skin Wound Care, 17(7):354, 356, 358−60, 362−64 (September 2004). NPL−581
【非特許文献707】 PAGE, J.C., et al., "Negative pressure wound therapy in open foot wounds with significant soft tissue defects", Ostomy Wound Manage., 51(2A suppl):9S−14S (February 2005); excerpted from Page, J.C., et al., "Retrospective analysis of negative pressure wound therapy in open foot wounds with significant soft tissue defects", Adv. Skin & Wound Care, 17(7):354−364, (2004). NPL−582
【非特許文献708】 PATTISON, P.S., et al., "Case report: Using dual therapies-Negative pressure wound therapy and modified silicone gel liner−−to treat a limb postamputation and dehiscence", Wounds, 17(8):233−40 (11 sheets) (August 2005). NPL−583
【非特許文献709】 RATLIFF, C.R., "Negative−pressure wound therapy. Adjunct relief for chronic wounds", Adv. Nurs. Pract., 12(7):47−9 (3 sheets) (July 2004) (Issue date: July 1, 2004). NPL−584
【非特許文献710】 SARSAM, S.E., et al., "Management of wound complications from cesarean delivery,"Obstet. Gynecol. Surv., 60 (7):462−73 (July 2005). NPL−585
【非特許文献711】 SCHAUM, K.D., "Payment perspective: Negative pressure wound therapy pumps and ostomy supplies", Ostomy Wound Manage., 51(3):20−22 (2 sheets) (March 2005). NPL−586
【非特許文献712】 SIMMAN, R., et al., "A comparative histological study of skin graft take with tie−over bolster dressing versus negative pressure wound therapy in a pig model: a preliminary study [brief communication]", Wounds, 16(2):76−80 (7 sheets) (February 2004). NPL−587
【非特許文献713】 STONE, P., et al., "Bolster versus negative pressure wound therapy for securing split−thickness skin grafts in trauma patients", Wounds, 16(7):219−23 (5 sheets) (2004) (Posted August 4, 2004). NPL−589
【非特許文献714】 WOLVOS, T., "Wound instillation with negative pressure wound therapy", Ostomy Wound Manage., 51(2A suppl):21S−26S (February 2005) NPL−590
【非特許文献715】 JETER, K., "Closed suction wound drainage system", JWOCN, 31(2):51 (1 sheet) (March − April 2004). NPL−591
【非特許文献716】 AGARWAL, J.P., et al., "Vacuum−assisted closure for sternal wounds: a first−line therapeutic management approach", Plast. Reconstr. Surg., 116(4):1035−1040 (September 15, 2005). NPL−592
【非特許文献717】 SJOGREN, J., et al., "The impact of vacuum−assisted closure on long−term survival after post−sternotomy mediastinitis", Ann. Thorac. Surg., 80(4):1270−5, (October 2005). NPL−593
【非特許文献718】 MENDEZ−EASTMAN, S., "New advances in wound therapy", printout from Woundsl.com; 7 sheets (April 15, 2005). NPL−594
【非特許文献719】 "Promoting wound healing", Nurses−Digest, 2(3), 6 sheets, March 2005. NPL−595
【非特許文献720】 ROYLANCE, L., "Nancy Sujeta, Amanda Clark,"DOME, volume 55, March 2004, 2 sheets of website printout www. hopkinsmedicine.org/dome/0405/feature4.cfm. NPL−596
【非特許文献721】 AGARWAL, J.P., et al., "Vacuum assisted closure TM for sternal wounds: a first line therapeutic management", ASPS, Plastic Surgery 2004, Philadelphia, PA, abstract (2 sheets) (Wednesday October 13, 2004). NPL−597
【非特許文献722】 GOMOLL, A.H., et al., "Incisional vacuum−assisted closure therapy", J. Orthop. Trauma, 20(10):705−709, (November − December 2006). NPL−599
【非特許文献723】 LEININGER, B.E., et al., "Experience with wound VAC and delayed primary closure of contaminated soft tissue injuries in Iraq", J. Trauma, 61(5):1207−1211 (November 2006). NPL−600
【非特許文献724】 GUPTA, S., ed., "Differentiating negative pressure wound therapy devices: an illustrative case series", Wounds, 19(1 suppl):1−9, (January 2007). NPL−603
【非特許文献725】 KORASIEWICZ, L.M., "Abdominal Wound With a Fistula and Large Amount of Drainage Status After Incarcerated Hernia Repair", Journal of Wound, Ostomy & Continence Nursing. 31(3):150−153, (May − June 2004). NPL−610
【非特許文献726】 GUNTINAS−LICHIUS, 0., et al., "The role of growth factors for disease and therapy in diseases of the head and neck", DNA and Cell Biol., 22(9):593−606, (September 2003). NPL−611
【非特許文献727】 GOLDMAN, R., "Growth factors and chronic wound healing: past, present, and future", Adv. Skin Wound Care, 17 (1):24−35, (January − February 2004). NPL−618
【非特許文献728】 MALLI, S., "Keep a close eye on vacuum−assisted wound closure", Nursing, 35(7):25 (July 2005). NPL−622
【非特許文献729】 LYNCH, J.B., et al., "Vacuum−assisted closure therapy: a new treatment option for recurrent pilonidal sinus disease. Report of three cases", Dis. Colon Rectum, 47(6):929−32 (June 2004) (Published online May 4, 2004). NPL−520
【非特許文献730】 MX: Business Strategies for Medical Technology Executives, (March/ April 2005). NPL−624
【非特許文献731】 NIEZGODA, J.A., "Incorporating negative pressure therapy into the management strategy for pressure ulcers", Ostomy Wound Manage., 50(11A suppl.):5S−8S, (November 2004). NPL−625
【非特許文献732】 BANWELL, P.E., Topical negative pressure therapy: advances in burn wound management", Ostomy Wound Manage., 50(11A suppl.):9S−14S, (November 2004). NPL−630
【非特許文献733】 KAPLAN, M., "Negative pressure wound therapy in the management of abdominal compartment syndrome", Ostomy Wound Manage., 50(11A suppl):20S−25S, (November 2004). NPL−626
【非特許文献734】 GUPTA, S., et al., "The perioperative use of negative pressure wound therapy in skin grafting", Ostomy Wound Manage., 50(11A suppl.):26S−28S, (November 2004). NPL−627
【非特許文献735】 SCHOEMANN, M.B., et al., "Treating surgical wound dehiscence with negative pressure dressings", Ostomy Wound Manage., 51(2A suppl.):15S−20S, (February 2005). NPL−628
【非特許文献736】 BOOKOUT, K., et al., "Case studies of an infant, a toddler, and an adolescent treated with a negative rpessure wound treatment system", J. Wound OstomyContinence Nurs., 31(4):184−192, (8 pp.) (July / August 2004). NPL−629
【非特許文献737】 BORKOWSKI, S., "G tube care: managing hypergranulation tissue", Nursing, 35(8):24 (August 2005). NPL−639
【非特許文献738】 MACHEN, M. S., "Management of traumatic war wounds using vacuum−assisted closure dressings in an austere environment," Army Medical Department J., pp. 17−23, (Jan. − Mar. 2007). NPL−688
【非特許文献739】 PECK, M.A., et al., "The complete management of extremity vascular injury in a local population: a wartime report from the 332nd Expeditionary Medical Group/Air Force Theater Hospital, Balad Air Base, Iraq," J. Vasc. Surg., pp. 1−9, (2007), (Presented at the Plenary Session of the Eastern Vascular Societys Twentieth Annual Meeting, Washington D. C., Sep. 30, 2006). NPL−689
【非特許文献740】 GIOVANNINI, U.M., et al., "Topical negative therapy and vacuum assisted closure. New strategies and devices in surgical reconstruction", Minerva Chir., 60(3):191−4 (June 2005). NPL−461
【非特許文献741】 PCT/US08/79364 − Written Opinion and International Search Report P04263W00−ISR (Dec. 16, 2008)
【非特許文献742】 BAGAUTDINOV, N.A., "Variant of external vacuum aspiration in the treatment of purulent disease of soft tissue," pp. 94−96 and Introduction by V.E. Volkov and an opinion by V. V. Shutova dated Feb. 4, 2009, in Russian with English translation, with alleged card catalogue card with English translation, and certification of translation dated Feb. 19, 2009, Current Problems in Modern Clinical Surgery, (1986). NPL−724
【非特許文献743】 KUZNETSOV, V.A., "Vacuum and vacuum−sorption treatment of open septic wounds," in II All−union conference "Wounds and wound infection" "(Abstracts of presentations)" in Russian with English translation, and card with English translation, Moscow, Oct. 28−29, 1986. NPL−725 (BAGAUTDINOV II)
【非特許文献744】 ROBSON, M.C., et al., Chapter 10 "Wounds and wound healing," p. 107−114 in Essentials of General Surgery, P.F. Lawrence ed., Williams & Wilkins, (1988). NPL−714
【非特許文献745】 SMITH, D.J. Jr., et al., Chapter 7 "Wounds and wound healing," p. 113−122 in Essentials of General Surgery, 3d edition, P.F. Lawrence ed., Lippincott Williams & Wilkins, (2000). NPL−716
【非特許文献746】 TALBOY, G.E., et al., "Chapter 8: Wounds and wound healing," p. 147−161 in Essentials of General Surgery, B. Sun ed., Lippincott Williams & Wilkins, (2006). NPL−717
【非特許文献747】 GARRISON, R.N., et al., "Chapter 9: Surgical infections," p. 163−179 in Essentials of General Surgery, B. Sun ed., Lippincott Williams & Wilkins, (2006). NPL−718
【非特許文献748】 SUMPIO, B.E., et al., "Role of negative pressure wound therapy in treating peripheral vascular graft infections," Vascular, 16(4):194−200, (2008). NPL−719
【非特許文献749】 TABERS Cyclopedic Medical Dictionary, Edition 20, pps: 306−309, 728−729, 765, 1726, and 2006−2009. (2005). NPL−720
【非特許文献750】 MILLS, N., Polymer Foams Handbook: engineering and biomechanics applications and design guide, pp. 2−3, (2007). NPL−722
【非特許文献751】 BUCKNALL, T.E., et al.. eds., "Sutures and dressings," p. 88−93 in Wound Healing for Surgeons, (1984). NPL−723
【非特許文献752】 PARKER, S.P., ed., McGraw−Hill Dictionary of Scientific and Technical Terms, 5th ed., pp. 139, 533, 772, and 1672 (1994). NPL−726
【非特許文献753】 ALGER, M.S.M., Polymer Science Dictionary, (4 sheets), Elsevier Science Publishers Ltd. (1989). NPL−729
【非特許文献754】 Stedmans Medical Dictionary, 25th ed., pp. 554, 667−668, and 1603−1604, Williams & Wilkins, (1990). NPL−730
【非特許文献755】 Websters New World Dictionary of the American Language, pp. 1105, Simon & Schuster, Inc., (1984). NPL−731
【非特許文献756】 Transeal transparent wound dressing, DeRoyal, 4 sheets (2003). NPL−733
【非特許文献757】 KUZNETSOV, V.A., "Vacuum and vacuum−sorption treatment of open septic wounds," in II All−union conference "Wounds and wound infections" "(Presentation abstracts)" in Russian with English translation dated Apr. 2, 2009, with table of contents, Moscow, Oct 28−29, 1986. NPL−734
【非特許文献758】 British Pharmacopoeia 19, Vol. II, p. 927 and p. 548 of 1986 addendum, (Vol. II − 1980, addendum − 1986). NPL−738
【非特許文献759】 KCI, "The V.A.C. operations summary," 7 sheets, (1999). NPL−732
【非特許文献760】 KANSHIN, N.N., "Closed treatment of suppurative processes by the method of active lavage drainage," Third Surgical Clinic of the N.V. Sklifosovkiy Moscow Scientific Research Institute of Emergency Care, pp. 18−23, (6 sheets in English, 6 sheets in Russian and English abstract on pages 22−23), allegedly submitted 1979. NPL−710
【非特許文献761】 LOKHVITSKII, S.V., et al., "External vacuum aspiration in the treatment of purulent disorders of the soft tissues," Inpatient Surgery Clinic of the Therapeutic Department at Karagandy Medical Institute, Municipal Hospital No. 1, Temirtau, pp. 130−134 (5 sheets English, 5 sheets Russian), allegedly submitted Sep. 22, 1982. NPL−709
【非特許文献762】 ERSH, Z. Ya., "Use of polyurethane foam for treating purulent cavities and wounds," Purulent Septic Unit of Hospital No. 35, (2 sheets English and 2 sheets Russian), allegedly submitted for publication Mar. 21, 1984. NPL−708
【非特許文献763】 3MTM Tegaderm TM Transparent film dressings − wound, Commonly asked questions, 4 sheets, (Jan. 2007). NPL−737
【非特許文献764】 GREENE, A.K., et al., "Microdeformational wound therapy," Ann. Plast. Surg., 56(4):418−422, (2006). NPL−713
【非特許文献765】 BUI, T.D., et al., "Negative pressure wound therapy with off−the−shelf components," Am. J. Surg., 192:235−237, (2006). NPL−706
【非特許文献766】 LARICHEV, A.B., et al., "Vacuum−therapy in the complex of treatment of festering wounds," Khirurgiia (Mosk.), 6:22−26, (13 sheets English translation, 5 sheets in Russian, English abstract on pp. 22), (2008). NPL−707
【非特許文献767】 SCHERER, S.S., et al., "The mechanism of action of the vacuum−assisted closure device," Plast. Reconstr. Surg., 122: 786−797, (presented at the Wound Healing Society Meeting 2007 in Tampa, Florida, Apr. 28 −May 1) (2008). NPL−712
【非特許文献768】 Tabers Cyclopedic Medical Dictionary, 16th edition, pp. 613−614, 643, 679, 1444, and 1686−1688, (1989). NPL−740
【非特許文献769】 PARKER, S.P., ed., McGraw−Hill Dictionary of Scientific and Technical Terms, 4th ed., pp. 1462, (1989). NPL−741
【非特許文献770】 Gove, P.B., ed., Websters Third New International Dictionary Unabridged, pp. 869 and 2627 (1986). NPL−742
【非特許文献771】 PEACOCK, Jr., E.E., Wound Repair, 3d edition, W.B. Saunders Company pp. 12−14, pp. 38−51, Chapter 6 Repair of skin wounds, (1984). NPL−721
【非特許文献772】 Spartanburg Regional Medical Center Operative reports, 35 sheets, dated 1989. NPL−747
【非特許文献773】 JOHNSON, F.E., "Expanded use of suction drains," pp. 469 and 1 sheet of drawings (allegedly dated 1985). NPL−748
【非特許文献774】 BROSSY, J.−J., "Foam elastomer dressings in surgery," SA Medical Journal, 59:559−560, (Apr. 1981). NPL−749
【非特許文献775】 GROVES, A.R., et al., "Silastic foam dressing: an appraisal," Annals of the Royal College of Surgeons of England, vol. 67, pp. 117−118 and additional page, (1985). NPL−750
【非特許文献776】 HARDING, K.G., et al., "Silastic foam dressing for skin graft donor sites - a preliminary report," Br. 4, Plast. Surg., 33:418−421, (1980). NPL−751
【非特許文献777】 MALONE, W.D., "Wound dressing adherence: a clinical comparitive study," Archives of Emergency Medicine, 4:101−105, (1987). NPL−752
【非特許文献778】 Moblvac II advertising materials, 4 sheets, allegedly dated 1984. NPL−753
【非特許文献779】 BUCKNALL, T.E. ed., et al., "Wound healing for surgeons," Introduction, Chapter 1 The healing wound, Chapter 2 Wound strength, Chapter 3 Factors affecting healing, Chapter 4 Sutures and dressings, Chapter 5 Clinical trials, Chapter 6 Skin healing and bums, and Chapter 7 The abdominal wall, (1984). NPL−754
【非特許文献780】 BRUBACHER, L.L., "To heal a draining wound," RN, 45(3):30−36 (Mar. 1982). NPL−755
【非特許文献781】 DAHLIN, P.A., et al., "Cerebrospinal fluid leak because of pressure sore fistula in a quadriplegic," Spine, 12(1):72−75, (1987). NPL−756
【非特許文献782】 DOWNIE, P.A., ed., Cashs textbook of medical conditions for physiotherapists, Chapter 1 Inflammation and healing, Chapter 2 Oedema, Chapter 19 Skin conditions, Chapter 20 Burns, B. Lippincott Co., (1979). NPL−757
【非特許文献783】 ERSH, Z. Ya., "Use of polyurethane foam for cleaning of purulent cavities and wounds,"I.I. Grekov J. of Surg., 133 (9):134−135 and additional sheets (10 sheets in English and 5 sheets in Russian) (1984). NPL−758
【非特許文献784】 FASOL, P., et al., "The foil vacuum dressing for the treatment of infected skin defects," Acta Chir. Austriaca 116−118, (2 sheets English and 3 sheets German) (1976). NPL−759
【非特許文献785】 GRUENDEMANN, B.J., et al., Alexanders Care of the patient in surgery, 8th ed., C.V. Mosby Co., pp. 138−139 (1987). NPL−761
【非特許文献786】 KIRK−OTHMER Encyclopedia of chemical technology, 3d ed., vol. 8, pp. 201−203 (1979). NPL−762
【非特許文献787】 KOSTYUCHENOK, B.M., et al., "Vacuum treatment of purulent wounds," Soviet Medicine, pp. 18−21, (4 sheets English, 4 sheets Russian, with English abstract on last page), (1984). NPL−763
【非特許文献788】 KUZIN, M.I., et al, "Method of vacuum treatment of wounds," Wounds and Wound Infection, pp. 348−350, (2 sheets) (1981). NPL−764
【非特許文献789】 TRANCHELL, H.G., et al., Circulatory Ulcers A Physicial Approach, John Wright & Sons Ltd., Bristol, Foreword, I. Ulcers: a comparison, II. The ulcer, pp. 44−47, and 54−55, (1960). NPL−766
【非特許文献790】 PARISH, L.C., et al., "The infected decubitus ulcer," Int. J. Dermatol., 28:643−647 (Dec. 1989). NPL−768
【非特許文献791】 DAVYDOV, Y.A., et al., "Device and method for vacuum therapy of purulent lactation mastites," Khirurgiya, (4):131−132, (Apr. 1988). DV15
【非特許文献792】 DAVIDOV, Y.A., et al., "Justifying the usage of forced early secondary sutures in treatment of purulent wounds by the vacuum therapy," Vestnik Chirugia 126−129, (2 sheets in English aDAVIDOV, Y.A., et al., "Justifying the usage of forced early secondary sutures in treatment of purulent wounds by the vacuum therapy," Vestnik Chirugia 126−129, (2 sheets in English and 3 sheets in Russian) (Mar. 1990). DV16nd 3 sheets in Russian) (Mar. 1990). DV16
【非特許文献793】 DAVYDOV, Y.A., et al., "Pathogenic mechanisms of the effect of vacuum therapy on the course of the wound process," Khirurgiya, 6:42−47 (7 sheets English and 8 sheets Russian, with English abstract on pp. 46−47) (1990). DV17
【非特許文献795】 DAVYDOV, Y.A., et al., "Bacteriological and cytological evaluation of vacuum therapy of purulent wounds", Vestnik khirurgii, 10:48−52, (5 sheets English, 5 sheets Russian, English abstract on pp. 52) (Received 1987). DV18
【非特許文献795】 DAVYDOV, Y.A., et al., "Vacuum therapy in the treatment of purulent lactation mastitis," pp. 66−70 (5 sheets English, 5 sheets Russian, English abstract on pp. 70) (Received 1986). DV19
【非特許文献796】 DAVYDOV, Y.A., et al., "Vacuum therapy in the treatment of acute purulent diseases of soft tissues and purulent wounds", Vest. Khir. 141(9):43−46 (6 sheets English, 6 sheets Russian, English abstract on pp. 46) (1988). DV20
【非特許文献797】 3M TM Inzisionsfolien − Produktubersicht, by 3M Medica, 6 annotated sheets. NPL−772
【非特許文献798】 APPLICATION for rationalization proposal, proposal entitled "Variant for vacuum treatment of purulent wounds," (4 sheets in English, 4 sheets in Russian, certificate of translation dated May 8, 2009), proposal allegedly executed Dec. 25, 1985 (Bagautdinov Ill). NPL−773
【非特許文献799】 BUSCHBAUM, H.J., ed., et al., Strategies in Gynecologic Surgery, pp. 203, Springer−Verlag, NY, (1986). NPL−774
【非特許文献800】 FLYNN, J−B. McC., et al., Technological Foundations in Nursing, pp. 506−507, Appleton & Lange, Norwalk, CT, (1990). NPL−775
【非特許文献801】 GOMCO Mobile constant and intermittent model 6030 & 6031, Operation, Maintenance and Service Manual, with annotations, 21 sheets, (Jan. 1987). NPL−776
【非特許文献802】 KAHLSON, G., et al., "Wound healing as dependent on rate of histamine formation," The Lancet, pp. 230−234, (Jul. 30, 1960). NPL−777
【非特許文献803】 KAREV, I.D., et al., "Foam drainage system for treating purulent wounds," pp. 87−88, (2 sheets English translation, 2 sheets Russian and certifcation of translation dated Apr. 6, 2009) (allegedly dated 1986). NPL−778
【非特許文献804】 KOZIER, B., et al., Techniques in Clinical Nursing, 3d ed., pp. 559−560, pp. 603−605, Addison−Wesley Publishing Company, Inc., Health Sciences, Redwood City, CA, (1989). NPL−779
【非特許文献805】 McLEAN, W. C., "The role of closed wound negative pressure suction in radial surgical procedures of the head and neck," The Laryngoscope, 74(1)70−94, (Jan. 1964). NPL−780
【非特許文献806】 NORTON, B.A., et al., Skills for Professional Nursing Practice: communication, physical appraisal, and clinical techniques, pp. 298−302, pp. 328−329, Appleton−Century−Crofts, Norwalk, CT (1986). NPL−781
【非特許文献807】 BAGAUTDINOV, N.A., Report on Practical Application entitled "Variant of vacuum treatment of purulent wounds," Kazan Municipal Hospital No. 8, (1 sheet in English, 1 sheet in Russian and certificate of translation dated May 8, 2009), (allegedly dated Dec. 24, 1985). (Practical Report I) NPL−782
【非特許文献808】 KUZNETSOV, V.A. et al., Report on Practical Application entitled "Method of vacuum−sorption treatment of purulent wounds," Kazan Municipal Hospital No. 8, (1 sheet in English, 1 sheet in Russian and certificate of translation dated Apr. 28, 2009) (allegedly dated May 19, 1986). (Practical Report II) NPL−783
【非特許文献809】 BAGAUTDINOV, N.A., Report on Practical Application entitled "Method of vacuum treatment of open purulent wounds," Medical−Sanitary Ward of the Arzamas Instrument Plant, (1 sheet in English, 1 sheet in Russian and certificate of translation dated Apr. 27, 2009) (allegedly dated 1986).(Practical Report III) NPL−784
【非特許文献810】 ROTH, B., et al., "Ubersichtsarbeit: Indication for suction−rinse drainage and hygienic certainty in drainages," GMS Krankenhaushyg. Interdiszip, 1(1):Doc27 (7 sheets in German with English abstract on first sheet) (2006). NPL−785
【非特許文献811】 SCHNEIDER, F.R., Handbook for the Orthopaedic Assistant, 2nd ed., pp. 185, The C.V. Mosby Company, St. Louis, (1976). NPL−786
【非特許文献812】 THOMAS, S., Wound Management and Dressings, Chapter 4: Semipermeable film dressings (continued onto pp. 26−34), Chapter 5: Foam dressings (continued onto pp. 36−42), and pp. 166, The Pharmaceutical Press, London, (1990). NPL−787
【非特許文献813】 WITKOWSKI, J.A., et al., "Synthetic dressings: wound healing in the 80s," (5 sheets), Hospital Therapy, (Nov. 1986). NPL−788
【非特許文献814】 Excerpts from Biers Hyperemic Treatment, pp. 17−25, 44−46, 90−96, 167−170, 210−211 (1909). NPL−767
【非特許文献815】 DEMOREST, R.L., "New standards in water vapour permeability testing," British Plastics & Rubber, 3 sheets, (handwritten label on first sheet shows "Exhibit TT"), (May 1995). NPL−789
【非特許文献816】 KIRK−OTHMER, Encyclopedia of Chemical Technology, 2nd completely revised edition, vol. 9, pp. 220−232, John Wiley & Sons, Inc., (1966). NPL−744
【非特許文献817】 Stedmans Medical Dictionary, 25th ed., pp. 1739, Williams & Wilkins, (1990). NPL−743
【非特許文献818】 Standard Operating Procedure, The determination of moisture vapour permeability (MVP) and water transmission rate (WTR), implementation date: Sep. 11, 2006 and QA Operational Laboratories Analytical Report dated Nov. 13, 2008. NPL−745
【非特許文献819】 British Pharmacopoeia Selections: (1988) Vol. II, p. 1126−1127, A223−A224; Addendum 1992, p. 1494; (1993) Vol. II, p. 1266, A218−A219. NPL−746
【非特許文献820】 SOLOVEV, V.A., "Treatment and prevention of suture failures after gastric resection," Dissertation abstract, with alleged index card, S.M. Kirov Gorky State Medical Institute, Gorky, U.S.S.R., (Exhibit I of Third party comments) (1988). NPL−769
【非特許文献821】 SOLOVEV, V.A., "The method of treatment of immature external fistulas in the upper gastrointestinal tract," S.M. Kirov Gorky State Medical Institute, Gorky, U.S.S.R., (Exhibit J of Third party comments) (1987). NPL−770
【非特許文献822】 THOMAS, S., "Wound Management and Dressings," The Pharmaceutical Press, London, 223 sheets, (1990). NPL−793
【非特許文献823】 WOOD, R.A.B., et al., "A new method for treatment of open granulating wounds," Surgical Dressings in the Hospital Environment, T.D. Turner, ed., et al., Surgical Dressings Research Unit, Welsh School of Pharmacy, Uwist, Cardiff, 8 sheets, (1975). NPL−797
【非特許文献824】 TURNER, T.D., ed., et al., Advances in Wound Management, including "The role of foam dressings in wound management" by S. Thomas, "Clinical aspects of Synthaderm(r)" by T. Martin, et al., "Lyofoam(r) − Used in the treatment of leg ulcers" by J. Creevy, and "Clinical experience of Silastic(r) foam dressing," by K.G. Harding; John Wiley & Sons, 17 sheets, (Proceedings dated Mar. 20−21, 1985) (1986). NPL−798
【非特許文献825】 KUZNETSOV, V.A., et al., Report on Practical Application entitled "Method of vacuum−sorption treatment of purulent wounds," Kazan Municipal Hospital No. 8, (1 sheet in English, 1 sheet in Russian and certificate of translation dated Apr. 28, 2009), (allegedly dated May 19, 1986). NPL−800
【非特許文献826】 THOMAS, S., "Pain and wound management," Community Outlook, pp. 11−13, 15 and one extra sheet, (Jul. 1989). NPL−803
【非特許文献827】 LIVSHITS, V.S., "Polymer dressings for wounds and burns (review)," All−Union Scientific−Research Institute for Medical Polymers, Moscow, pp. 515−522, (allegedly published in Pharmaceutical Chemical Journal, 22(7):790−798, translated from Russian (allegedly dated Jul. 1988)), Plenum Publishing Corp., (1989). NPL−804
【非特許文献828】 CALNE, S., ed., Position Document: Pain at wound dressings changes, pp. 1−17 and 3 additional sheets, supported by Molnlycke Health Care, (allegedly dated 2002). NPL−805
【非特許文献829】 SKOVER, G., et al., "45: New Technologies: An Overview," Chronic Wound Care, pp. 425−430 (allegedly dated 1990). NPL−806
【非特許文献830】 2 sheets of documents, the citation is alleged to be: David JA, Wound Management: A Comprehensive Guide to Dressing and Healing, pp. 51−51 (allegedly dated 1986). NPL−807
【非特許文献831】 THOMAS, S., "Selecting dresssings," Community Outlook, Vol. 6, 4 sheets, (Jun. 1991). NPL−796
【非特許文献832】 1 sheet document, the citation is alleged to be: David J., Extract from Practical Nursing Handbook: Wound Management: A Comprehensive Guide to Dressing and Healing, pp. 166−167, (allegedly dated 1986). NPL−799
【非特許文献833】 DUNPHY, J.E., ed., et al., "Current Surgical Diagnosis & Treatment" 5th ed., pp. 946−951, with 5 additional sheets, Lange Medical Publications, Los Altos, CA (1981). NPL−809
【非特許文献834】 British Pharmacopoeia, Vol II, pp. 903−940, London (1980). NPL−801
【非特許文献835】 British Pharmacopoeia 1980, pp. A81, 542, 546−549, with annotations, London − Addendum (1986). NPL−802
【非特許文献836】 WAGNER, D.R., et al., "Combined parenteral and enteral nutrition in severe trauma," Nutrition in Clinical Practice, 7:113−116 with additional sheet, (1992). NPL−810
【非特許文献837】 KRIZEK, T.J., et al., "The use of prophylactic antibacterials in plastic surgery: A 1980s update," Plast. Reconstr. Surg., 76(6): 953−962, (Dec. 1985). NPL−811
【非特許文献838】 BAGAUTDINOV, N.A., "Variant of external vacuum aspiration in the treatment of purulent diseases of soft tissues," Current Problems in Modern Clinical Surgery, Interdepartmental Collection, Cheboksary, pp. 94−96, and library card, in English and Russian, (KCI_Con00220647−59) (1986). NPL−841
【非特許文献839】 KUZNETSOV, V.A., et al., "Vacuum and vacuum−sorption treatment of open purulent wounds," II All−Union Conference "Wounds and Wound Infections" Moscow, pp. 91−92, with library card and table of contents, in English and Russian, (KCI_Con00220660−89) (1986). NPL−842
【非特許文献840】 WILLIAMS, R.S., "A simple technique for successful primary closure after excision of pilonidal sinus disease," Ann. R. Coll. Surg. England, 72:313−315, (only 2 sheets provided), (1990). NPL−820
【非特許文献841】 GRAY, A.J., et al., "Small bowel perforation following vacuum suction drainage," J. R. Coll. Surg. Edinb. 30(5):324−5 and additional sheet, (Oct. 1985). NPL−819
【非特許文献842】 KUMAR, A.R., "Standard wound coverage techniques for extremity war injury," J. Am. Acad. Orthop. Surg., 14:S62− S65, (2006). NPL−827
【非特許文献843】 HELGESON, M.D., et al., "Bioartificial dermal substitute: A preliminary report on its use for the management of complex combat−related soft tissue wounds," J. Orthop. Trauma, 21(6):394−399, (Jul. 2007). NPL−828
【非特許文献844】 INGARI, J.V., et al., "Civilian and detainee orthopaedic surgical care at an air force theater hosptial," Tech. Hand Upper Extr. Surg., 11(2):130−134, (2007). NPL−829
【非特許文献845】 COVEY, D.C., "Combat orthopaedics: A view from the trenches," J. Am. Acad. Orthop. Surg., 14:S10−S17, (2006). NPL−830
【非特許文献846】 ANDERSEN, R.C., et al., "Definitive treatment of combat casulties at military medical centers," J. Am. Acad. Orthop. Surg., 14:S24−S31, (2006). NPL−831
【非特許文献847】 WAGNER, D. R., et al., "Bioelectrical impedance as a discriminator of pressure ulcer risk," Adv. Wound Care, 9 (2):30−37, (1996). NPL−834
【非特許文献848】 MULDER, G.D., et al., "Prospective randomized study of the efficacy of hydrogel, hydrocolloid, and saline solution−moistened dressings on the management of pressure ulcers," Wound Rep. Reg., 1:213−218, (1993). NPL−836
【非特許文献849】 TINTLE, T.E., et al., "Early experience with a calcium alginate dressing," Ostomy/Wound Management, pp. 74−81, (May/Jun. 1990). NPL−839
【非特許文献850】 JETER, K.F., et al., "Comprehensive wound management with a starch−based copolymer dressing," J. Enterostom. Ther., 13(6):217−225, (Nov. − Dec. 1986). NPL−840
【非特許文献851】 WINTER, G.D., "Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig," Nature, no. 4812, p. 293−294 (Jan. 20, 1962). NPL−816
【非特許文献852】 ROBSON, M.C., et al., "Bacterial quantification of open wounds," Military Medicine, pp. 19−24, (Jan. 1969). NPL−817
【非特許文献853】 JACKSON, D.M., "The diagnosis of the depth of burning," Br. J. Surgery, 40(164):588−596 and 7 additional sheets, (May 1953). NPL−81
【非特許文献854】 Morykwas, M.J., "38: Vacuum−assisted closure of wounds" in "Wound Healing," A. Falabella et al., eds., Taylor & Francis, NY, pp. 503−515, (2005). WFU−77
【非特許文献855】 DeFranzo, A.J., et al., "Vacuum assisted closure for the treatment of abdominal wounds," Clin. Plast. Surg. 33(2): 213−224 (Apr. 2006). WFU−78
【非特許文献856】 DEFRANZO, A.J., et al., "Vacuum−assisted closure for defects of the abdominal wall," Plast. Reconstr. Surg., 121 (3):832−839, (Mar. 2008). WFU−79
【非特許文献857】 PARK, C.A., et al., "Breast asymmetry: presentation of a giant fibroadenoma," Breast J., 12(5):451−461, (2006). VVF U−80
【非特許文献858】 ZANNIS, J., et al., "Comparison of fasciotomy wound closures using traditional dressing changes and the Vacuum−Assisted Closure device," Ann. Plast. Surg., 62(4):407−409, (Apr. 2009). WFU−81
【非特許文献859】 THOMPSON, J.T., et al., "Outcome analysis of helmet therapy for positional plagiocephaly using a three−dimensional surface scanning laser," J. Craniofasc. Surg., 20(2):362−365, (Mar. 2009). WFU−82
【非特許文献860】 ARGENTA, L.C., et al., "Advances in hemangioma evaluation and treatment," J. Craniofac. Surg., 17(4):748−755 (Jul. 2006). WFU−83
【非特許文献861】 PLIKAITIS, C.M., et al, "Neurocutaneous melanosis: clinical presentations," J. Craniofac. Surg., 16(5):921−925 (Sep. 2005). WFU−84
【非特許文献862】 DAVID, L.R., et al., "Proboscis lateralis: a rare craniofacial anomaly, reconstruction, and long−term evaluation," J. Craniofac. Surg., 19(4):1107−1113, (July 2008). WFU−85
【非特許文献863】 SANGER, C., et al., "Dynamic spring mediated cranioplasty in an experimental model with resorbable foot plates," J. Craniofac. Surg., 18(1):54−59, (Jan. 2007). WFU−87
【非特許文献864】 MORYKWAS, M.J., et al., "Vacuum−assisted closure: state of basic research and physiologic foundation," Plast. Reconstr. Surg., 117(7) (Suppl): 121S−126S, (Jun. 2006). WFU−88
【非特許文献865】 HILL, C.A., et al., "Superior sternal cleft repair using autologous rib grafts in an infant with complex congenital heart disease," Ann. Thorac. Surg., 84:673−4, (2007). WFU−89
【非特許文献866】 MCGEE, M.P., et al., "Swelling and pressure−volume relationships in the dermis measured by osmotic−stress technique," Am. J. Physiol. Regul. Integr. Comp. Physiol., 296:R1907−R1913, (Mar. 25, 2009). WFU−90
【非特許文献867】 MORYKWAS, M., "Vacuum assisted closure," 91 sheets of slides. WFU−91
【非特許文献868】 MORYKWAS, M., et al., "El use de la plantilla de regeneracion integra en la cirugia reconstructiva," 121 sheets of slides. WFU−92
【非特許文献869】 ARGENTA, A., et al., "Deformation of superficial and deep abdominal tissues with application of a controlled vacuum", 1 sheet. WFU−94
【非特許文献870】 Proto, Massachusetts General Hospital Dispaches from the Frontiers of Medicine, 2 sheets, (Winter 2006). NPL−813
【非特許文献871】 POWELL, E.T., "The role of negative pressure wound therapy with reticulated open cell foam in the treatment of war wounds," J. Orthop. Trauma, Vol. 22(10) Supp.: S138−S141, (Nov./Dec. 2008). NPL−814
【非特許文献872】 "Negative pressure wound therapy devices," Technology assessment report; Agency for Healthcare Research and Quality, with annotations, website dated May 26, 2009, printed June 26, 2009 and June 28, 2009. NPL−812
【非特許文献873】 THOMAS, S., "Atraumatic dressings," World Wide Wounds, sponsored by Molnylcke Health Care, 11 sheets, published Jan. 2003, website printout dated Jun. 29, 2009. NPL−808
【非特許文献874】 ORGILL, D.P., et al., "The mechanisms of action of vacuum assisted closure: More to learn," Surgery, 146(1):40−51, (Jul. 2009). WFU−98
【非特許文献875】 DEFRANZO, A., et al., "4: Vacuum−assisted closure in extremity trauma," in Soft Tissue Surgery, S.L. Moran et al., p. 49−60 and additional sheet, Lippincott Williams & Wilkins (Pub. Apr. 1, 2008). WFU−96
【非特許文献876】 STOECKEL, W.T., et al., "30: Vacuum assisted devices for difficult wounds of the face and neck," Essential Tissue Healing of the Face and Neck, p. 399−408, and additional sheet, Flom, et al., (Pub. Jan. 28, 2009). WFU−95
【非特許文献877】 MARKS, M.W., et al., "Principles & Applications of Vacuum Assisted Clbsure (VAC)" Plastic Surgery Secrets, 2nd ed., Mosby Elsevier, (2010). WFU−97
【非特許文献878】 BONNAMY, C., et al., "Use of the vacuum−assisted closure system for the treatment of perinea! gangrene involving the abdominal wall", Ann. Chir., (English abstract on first page and 1 sheet PubMed abstract) 125(10):982−4 (December 2000). NPL−054
【非特許文献879】 MEYER, W., et al., excerpts from "Biers Hyperemic Treatment", W.B. Saunders and Co., (48 sheets) (1908). NPL−702
【非特許文献880】 WONG, S.L., et al., "Loxoscelism and negative pressure wound therapy (Vacuum−assisted closure): a clinical case series," Am. Surg., 75:1128−1131, (Nov. 2009). WFU−86
【非特許文献881】 COVEY, D.C. et al., "Orthopaedic war injuries: From combat casulty care to definitive treatment: A current review of clinical advances, basic science, and research opportunities," Instr. Course Lect. 57:65−86 (2008). NPL−821
【非特許文献882】 PIRELA−CRUZ, M.A., et al., "Management of large soft−tissue wounds with negative pressure therapy − lessons learned from the war zone," J. Hand Ther. 21:196−203, (2008). NPL−823
【非特許文献883】 VERTREES, A., et al., "Modern management of complex open abdominal wounds of war: A 5−year experience," J. Am. Coll. Surg., 207:801−809, (2008). NPL−824
【非特許文献884】 GEIGER, S., et al., "War wounds: Lessons learned from Operation Iraqi Freedom," Plast. Reconstr. Surg., 122:146−153, (2008). NPL−825
【非特許文献885】 HOSPENTHAL, D.R., et al., "Guidelines for the prevention of infection after combat−related injuries," J. Trauma, 64(3): S211−S220, (2008). NPL−832
【非特許文献886】 MURRAY, C.K., et al., "Prevention and management of infections associated with combat−related extremity injuries," J. Trauma, 64(3):S239−S251, (2008). NPL−833
【非特許文献887】 CAMPBELL, P.E., et al., "Retrospective clinical evaluation of gauze−based negative pressure wound therapy," Int. Wound J., 5(2):280−286, (2008). NPL−837
【非特許文献888】 PCT/US08/30581 − Written Opinion and International Search Report P04486W00 − ISR (Feb. 20, 2009).
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【発明の概要】
【課題を解決するための手段】
これまで、上記の病態の治療は、芳しい成果を上げていない。脊髄の外科的減圧は、不可逆的圧縮を防ぐ上で有益な場合もある。マンニトールその他のいくつかの浸透圧剤などの薬剤は、浮腫に起因した髄腔内圧を軽減することができる。これらの場合におけるステロイドの価値は不確かで、最近は高圧酸素の適用が提案されている。
上記を受け、損傷した皮膚組織および皮下組織に陰圧(または準大気圧)を適用する療法では、従来の方法と比べ、治癒が早まることが実証されており(米国特許第5645081号、第5636643号、第7198046号、および第7216651号のほか、米国特許公開第2003/0225347号、第2004/0039391号、および第2004/0122434号に開示されている。これらの内容は参照により本明細書に組み込むものとする)、脊髄の特定組織に特に適した装置および方法がいまだ必要とされている。
本発明では、損傷した脊髄組織に対し、準大気圧(または陰圧)を使って治療を行う装置および方法を提供し、前記損傷した脊髄組織とは、疾患、感染、または外傷により損傷した脊髄組織など、間質浮腫の二次的な結果として腫脹、圧力増加、および血流機能の低下につながるおそれのあるものである。例えば、脊髄は鈍的外傷により損傷を受け、回復可能または回復不可能な損傷に至る可能性がある。
本発明の一態様では、準大気圧を使って、損傷した脊髄組織を治療する方法を提供する。この方法は、多孔質材料の1若しくはそれ以上の細孔と前記損傷した脊髄組織との間に気体流通を提供するため、前記損傷した脊髄組織に近接させて前記多孔質材料を配置する工程を有する。損傷した脊髄組織に近接した原位置(in situ)で前記多孔質材料を密閉すると、損傷した脊髄組織の周辺領域で準大気圧を保つことができる。前記多孔質材料は、損傷した脊髄組織において準大気圧を発生するための減圧システムと動作可能に連結でき、前記減圧システムを作動させると、損傷した脊髄組織において準大気圧を提供することができる。この準大気圧は、損傷した脊髄組織における浮腫を軽減する上で十分な時間、この脊髄組織において維持することができる。例えば、前記準大気圧は、大気圧より約25mmHg低い圧力で維持することができる。この方法には、損傷した脊髄組織において準大気圧を維持するため、当該損傷した脊髄組織の上からカバーを配置する工程と、当該損傷した脊髄組織に近接した組織を前記カバーで密閉する工程とを含めることもできる。前記カバーは、粘着シートの形態で提供でき、損傷した脊髄組織の上から配置することができる。そのような場合、前記カバーを密閉する工程には、損傷した脊髄組織周囲の組織に前記粘着シートを接着させて密閉し、前記シートと前記損傷した脊髄組織周囲の組織との間にシール(密閉部)を形成する工程を含めることができる。
本発明の別の一態様では、損傷した脊髄組織を治療する機器を提供する。この機器には、オープンセル構造のコラーゲン材料など、生体に導入可能な多孔質材料を含めることができ、当該多孔質材料は、その1若しくはそれ以上の細孔と治療すべき脊髄組織との間の気体流通を可能にするよう構成された細孔構造を有する。生体に導入可能な前記多孔質材料の性質により、当該多孔質材料を取り出す第2の処置は不要になる(本明細書における用語「生体に導入可能」(bio−incorporable)は、患者体内に無期限に残すことのできる材料のうち、再構築される骨の一部となり、骨中へと再吸収され、溶解し、および/または同化または修飾されることが可能な材料を説明するため定義されている)。前記機器には、準大気圧を発生する減圧源も含まれ、この減圧源は、前記多孔質材料と気体流通可能に設けて、前記脊髄組織に前記準大気圧を分布させることができる。前記多孔質材料は、その少なくとも1つの選択された表面において、当該多孔質材料の内部での組織の成長を防ぐ上で十分小さな細孔を有する。また、前記多孔質材料は、その少なくとも1つの選択された表面において、線維芽細胞のサイズより小さい細孔径を有することができ、前記選択された表面以外の位置において、線維芽細胞および脊髄細胞より大きな細孔径を有することができる。前記多孔質材料の細孔径は、アルブミンのサイズのタンパク質が通過できるようにする上で十分な大きさにできる。また、前記生体に導入可能な多孔質材料は、準大気圧の伝達を防ぐよう密閉された少なくとも1つの表面を有することができる。当該機器には、カバーを含めることもでき、当該カバーは、前記損傷した脊髄組織を覆い、当該カバー下の当該損傷した脊髄組織において準大気圧を保つよう構成される。
このように、本発明は、病理学的過程の進行を最小限に抑え、脊髄の生理学的完全性が損なわれるのを最小限に抑え、脊髄の血流および栄養供給の機能低下を最小限に抑える装置および方法を提供するものである。脊髄の浮腫および髄腔内圧を軽減することにより、脊髄のヘルニア形成および機能低下のリスクを最小限に抑えることができる。また、本発明は、脊髄内組織の炎症反応および神経病理学的反応を助長するメディエーター、分解生成物、および毒性物質の排除を促進する。
本発明の好適な実施例に関する上記の要約および下記の詳細な説明は、以下の添付の図面と併せて読むと最もよく理解される。
図1は、準大気圧の適用前に原位置(in situ)に配置した本発明の機器の例示的構成を概略的に示した一部断面図である。 図2は、図1の一部断面図で、準大気圧が適用されている状態を概略的に例示した図である。 図3は、図1および図2の一部断面図で、適用された準大気圧が脊髄周囲の組織に及ぼす作用を概略的に例示した図である。 図4は、原位置(in situ)に配置された本発明の第2の例示的構成を概略的に示した一部断面図で、この構成では、剛性または半剛性のカバーが脊髄の上から皮下に配置されている。 図5は、原位置(in situ)に配置された本発明の第3の例示的構成を概略的に示した一部断面図で、この構成では、柔軟なカバーが脊髄の上から皮下に配置されている。 図6は、脊髄に回復可能な鈍的外傷を与えた対照群ラットのBBBスコア(Basso,Beattie and Bresnahan(BBB)Locomotor Rating Scale)を、時間の関数として例示した図である。 図7は、脊髄に回復可能な鈍的外傷を与えて準大気圧で治療したラット群のBBBスコアを、時間の関数として例示した図である。 図8は、脊髄に回復不可能な鈍的外傷を与えた対照群ラットの脊髄の断面積を、時間の関数として示した図である。 図9は、脊髄に回復不可能な鈍的外傷を与えて準大気圧で治療したラット群の脊髄の断面積を、時間の関数として示した図である。 図10は、本発明の準大気圧機器に使用するための多層構造を有する多孔性材料を概略的に例示した図である。
ここで各図を参照すると、全体にわたり同様な要素は同様な参照番号により示されており、本発明は、損傷した脊髄組織を準大気圧(または陰圧)で治療する装置および方法に関し、この場合「損傷した」(damaged)組織は、例えば外傷、疾患、感染、手術による合併症、または他の病理学的過程による損傷など、損傷し、機能が低下し、または他の任意の態様で障害が生じた組織を含むものとして定義される。より具体的にいうと、本発明の装置および方法は、上述した原因など任意の原因により二次的に生じる脊髄柔組織の浮腫の治療と、硬膜下または硬膜外の空間を含んだ脊髄を取り囲む任意の空間の治療と、上述した原因など任意の原因で上昇した髄腔内圧の治療とを可能にする。
本発明の準大気圧脊髄治療装置100の例示的な構成には、脊髄7に近接させた多孔質材料10に、管20を通じて準大気圧を供給する減圧源30が含まれる。この場合、前記多孔質材料10は、脊髄7に準大気圧を送達し、分布させるよう構成することができる。本脊髄治療装置100は、前記損傷した脊髄組織7に近接させて多孔質材料10を配置し、前記多孔質材料10の1若しくはそれ以上の細孔と前記損傷した脊髄組織7との間に気体流通を提供するよう患者に適用することができる。管20の遠端22を前記多孔質材料10に連結し、縫合糸8で皮膚および皮下組織2を縫合すると、前記多孔質材料10を原位置(in situ)で密閉して、損傷した脊髄組織7の周辺領域で準大気圧を保つことができる。前記管20の近端24を減圧源30に取り付けると、この減圧システム30に前記多孔質材料10を動作可能に連結して、当該減圧システム30の作動時、前記損傷した脊髄組織7に準大気圧を生じることができる。
図1を詳しく参照すると、患者体内の原位置(in situ)で患者体内の組織に取り囲まれた状態で、本発明の準大気圧脊髄治療装置100の例示的な構成の一部断面図が示されている。例示されている組織には、前記皮膚および皮下組織2と、僧帽筋3や脊柱起立筋4などの筋肉組織と、脊椎5と、横突起6と、脊髄7とが含まれている。脊髄7へのアクセスを提供するため、前記脊椎5の一部は欠落している可能性がある。例えば、切離手術、疾患、または負傷により、棘突起がない可能性がある。オープンセル構造のコラーゲン材料などの多孔質材料10は、準大気圧治療を施術する脊髄組織7に近接させて皮下空間に配置し、例えば柔組織内の浮腫を軽減して生理学的機能を改善することができる。オープンセル構造のコラーゲン材料に加え、この多孔質材料10には、例えばポリグリコール酸材料および/またはポリ乳酸材料、合成ポリマー、柔軟なシート状メッシュ、オープンセル構造のポリマー発泡材、発泡材部分、多孔質シート、ポリビニルアルコール系発泡材、ポリエチレン材料および/またはポリエステル材料、エラスチン、ヒアルロン酸、アルギン酸塩、ポリジオールクエン酸塩(polydiolcitrate)、ポリヒドロキシブチラート(polyhyrdoxybutyrate)、ポリヒドロキシフマラート(polyhyrdoxyfumarate)、ポリトリメチレンカーボネート、ポリグリセロールセバケート(ポリグリセロールセバシン酸)脂肪族または芳香族のポリ無水物、または他の適切な材料、およびこれらを任意に組み合わせてエレクトロスピニング、成形、または印刷により製造できるものを含めることもできる。このような材料としては、キトサン溶液(2%酢酸中1.33重量%または1.33体積%、合計体積20ml)などがあり、適切にサイズ調整された型(モールド)に注入することができる。その溶液を−70℃で2時間冷凍したのち、減圧した凍結乾燥機に24時間入れる。この材料を、2.5%〜5%のグルタルアルデヒド蒸気で12〜24時間(または紫外線を8時間照射して)架橋結合すると、成形された多孔質材料10が得られる。
また、前記多孔質材料10は、ポリカプロラクトン(polycaprolactone:PCL)を成形して作製することもできる。ポリカプロラクトンは、塩化ナトリウムと混合し(カプロラクトンと塩化ナトリウムの比は1:10)、十分な量のクロロホルム内に配置して成分を溶解させることができる。例えばこの溶液8mlは、適切にサイズ調整および成形された容器に注いで12時間乾燥させ、その後、水で24時間塩化ナトリウムを浸出させることができる。
また、前記多孔質材料10には、エレクトロスピニングした材料も使用できる。エレクトロスピニングした多孔質材料10を作製する配合および方法の一例を、タイプIコラーゲンと、コンドロイチン6硫酸(chondroitin−6−sulfate:CS)と、ポリ(1,8−オクタンジオールクエン酸塩)(poly 1,8−octanediol citrate:POC))と組み合わせを、76%:4%:20%の重量比で使って実施した。このコラーゲン・CS・POC配合には、2つの溶剤を利用した。すなわち、CSは水に溶解し、コラーゲンおよびPOCは2,2,2−トリフルオロエタノール(trifluoroethanol:TFE)に溶解した。次いで、水20%およびTFE 80%の溶液(体積/体積)を使用した。エレクトロスピニングを行う際には、コラーゲン:CS:POC混合物を含んだ溶液3mlを、18Ga(18ゲージ)の針を取り付けたシリンジに配置した。この溶液を、シリンジポンプ(New Era Pump Systems社、米国ニューヨーク州Wantaugh)を使って、2.0ml/時間で前記針の先端から吐出した。高電圧電源(HV Power Supply、Gamma High Voltage Research社、米国フロリダ州Ormond Beach)により、前記針部材(アノード)と接地されたコレクタ(カソード)との間の15〜25cmの距離に10〜20kVの電圧を印加した。次に、その材料をグルタルアルデヒド(グレードII、25%溶液)で架橋結合し、48時間熱重合(80℃)した。また、タイプIコラーゲンの多孔質材料10を、1,1,1,3,3,3−ヘキサフルオロ−2−プロパノール(1,1,1,3,3,3−hexafluoro−2−propanol:HFP)中にコラーゲン80mg/mlの初期濃度で開始し、上記のコラーゲン::CS:POCの組み合わせと同じエレクトロスピニング条件を使って、エレクトロスピニングすることも可能である。
多孔質材料10を作製するもう1つの方法は、熱インクジェット印刷技術を使用することである。その場合、コラーゲン、弾性材料、ヒアルロン酸、アルギン酸塩、およびポリ乳酸・ポリグリコール酸共重合体(コポリマー)など、生体に導入可能な材料を印刷することができる。その例として、タイプIコラーゲン(Elastin Products Co.社、米国ミズーリ州Owensville)を0.05%酢酸に溶解したのち、水で1mg/mlに希釈したもの、またアルギン酸ナトリウム(Dharma Trading Co.社、米国カリフォルニア州San Raphael)の1mg/ml水溶液が印刷可能である。タイプIコラーゲン(0.05%酢酸中2.86mg/ml)およびポリ乳酸・ポリグリコール酸(PURAC America社、米国ネブラスカ州Blair)(テトラグリコール(Sigma Aldrich社、米国ミズーリ州St.Louis)中14.29mg/ml)の混合物も、印刷できる。ハードウェアとしては、カートリッジ用にステッパーモーターおよびキャリッジを含んだHewlett Packard 660cプリンタを、プラットフォームに搭載できる。層状に印刷するには、プラットフォーム上のハードウェアの高さを調整する。
前記多孔質材料10については、脊髄7とのインターフェース(界面)に十分小さな細孔を有する(例えば線維芽細胞および脊髄細胞のサイズより細孔径を小さくする)ことにより、当該多孔質材料10内へと組織が成長するのを防ぐことができるが、そうしないと脊髄7に付着してしまい、取り外し時に出血または損傷を生じてしまう。また、この多孔質材料10と脊髄7との間のインターフェースにおける細孔径を十分小さくすると、脊髄7の生理学的機能を妨げる肉芽組織または瘢痕組織が当該脊髄7で過度に生成されるのを回避することができる。また同時に、この多孔質材料10の細孔径は、アルブミンサイズのタンパク質が通過できるようにして、メディエーター、分解生成物、および毒性物質など望ましくない化合物の排除が可能になるよう十分な大きさにすることができる。
ただし、この多孔質材料10は、当該多孔質材料10の内部または脊髄組織7に接触していない全位置では、より大きな(線維芽細胞および脊髄細胞より大きな)細孔径を有してよい。例えば、多孔質材料110の場合は、多孔質材料110内部での組織成長を生じない層(非内部成長層)112を伴った多層構造を有することができ、この非内部成長層112は、脊髄に隣接させても組織の内部成長を防ぐ上で十分小さな細孔径を有し、当該多孔質材料110は、さらに前記非内部成長層112より大きな細孔径を有する材料でできた追加層114を、前記非内部成長層112に接触して有することもできる。
あるいは、前記多孔質材料10は、均一な組成および/または形態にしてもよい。この多孔質材料10は、脊髄7とのインターフェースから離れた位置では、脊髄破壊が生じた領域で肉芽組織を促進するなど、当該脊髄7を取り囲む空間内の他組織で肉芽組織形成を促進するよう、十分大きな細孔径を有することができる。また、この多孔質材料10は、その表面のうち少なくとも1つが準大気圧を伝達すると同時に、他の1若しくはそれ以上の側部または側面からは準大気圧が伝達されないよう、それらの側部または側面が密閉された構成を有することもできる。このような構成を有する多孔質材料10では、その1側面に隣接する組織だけを優先的に治療することができる。例えば、脊髄7の柔組織は、前記多孔質材料10の密閉されていない側のインターフェースで治療することが可能である。
前記多孔質材料10は、準大気圧治療の施術後に取り出す必要のある材料から成るものであってよく、その場合は第2の手術が必要となる可能性がある。あるいは、前記多孔質材料10は、第2の手術を回避するため、コラーゲンなどの生体吸収性材料または経時的に無害に分解する材料から成るものであってよい。また、当該多孔質材料10は、この多孔質材料10が患者体内にある(in situ)間にMRI(磁気共鳴映像法)を実施できるよう、非金属材料を有するものであってよい。この多孔質材料10は、脊髄7に対して押された場合に脊髄の機能を妨げないよう、十分コンプライアント(柔軟)な材料も有することができる。同時に、この多孔質材料10は、脊髄機能を妨げるおそれのある「正常な脊髄」に対し、押し潰されずに引張りまたは変形の作用をもたらすよう、十分強固な材料を有することができる。
この多孔質材料10を通じて脊髄7に準大気圧を送達するため、管20は、その遠端で、当該多孔質材料10と気体流通可能に直接的または間接的に連結される。例えば、この管20の遠端22は、前記多孔質材料10に埋め込んでも、前記多孔質材料10上に配置してもよい。この管20の遠端22には、前記多孔質材料10および脊髄7への準大気圧の送達を助けるよう、1若しくはそれ以上の窓(孔)を含めてもよい。この管20が貫通する皮膚および皮下組織2の開口部の周囲を縫合糸8で固定すると、当該管20周囲の密閉に役立つ。この管20の近端24は、当該管20を通じて前記多孔質材料10および脊髄7に準大気圧を適用するよう、真空ポンプなどの減圧源30と動作可能に連結できる。
前記減圧源30には、コントローラ32を含めて準大気圧の発生を調整するようにできる。例えば、連続的または断続的に準大気圧を生じるよう前記減圧源30を構成すると、オン・オフのサイクルで準大気圧を発生する期間または発生しない期間を交互に提供するなどが可能になる。その発生および非発生のデューティサイクルは、1〜10(オン/オフ)から10〜1(オン/オフ)までの範囲であってよい。また、断続的に準大気圧を適用する場合は、これを定期的に行っても、正弦波などの周期的波形により行ってもよい。この減圧源30は、初期の治療後、より生理学的な状態を模倣するため、1分間あたり数回など周期的な設定を行うこともできる。その場合は、脊髄7内圧の監視結果を判断し、必要に応じて準大気圧を周期的にオン・オフ設定できる。全般的に、この減圧源30は、準大気圧が脊髄7の出血その他の有害事象を招くおそれを最小限に抑えるよう、大気圧から、大気圧より75mmHg低い圧力までの範囲の準大気圧を送達するよう構成することができる。このような準大気圧を適用すると、脊髄7から浮腫を除去するよう作用して、神経機能を保ち、より生理学的に維持された状態で回復および生存の確率を高めることができる。
脊髄7での準大気圧維持を支援するため、図4および図5のように柔軟なカバーまたはシート50、あるいは剛性の(または半剛性の)カバー40を脊髄7に近接させて設け、脊髄7周囲に準大気圧を維持する領域を提供することができる。図4および図5を参照して具体的に説明すると、カバー40、50は、脊髄7に近接した組織に接着させて、脊髄7および多孔質材料10の周囲に密閉領域48、58を画成するよう、脊髄7および多孔質材料10の上方から設けることができる。例えば、このカバー40、50は、フィブリン接着剤などの接着剤42を使って、脊椎5、筋肉組織4、および/または他の適切な組織に接着させることができる。前記接着剤42は、常温重合する接着剤を有してよく、さらに/または当該接着剤42を増量することにより、当該接着剤42が接触する潜在的に不規則な面を伴った形状に適合できるようにする充填剤を含むことが望ましい。この接着剤42は、前記カバー40、50とは別個の構成要素として、または前記カバー40、50の一部として提供でき、後者の場合は粘着カバー40、50が提供される。例えば、前記カバー50は、その表面のうち1若しくはそれ以上に適切な接着剤を含む柔軟な粘着シートを有することができる。
前記柔軟なカバー50の場合、その外縁部(エッジまたはボーダー)は、脊髄7の下(または脊髄7へ向かって)に巻き込むようにできる。あるいは図5のように、この柔軟なカバー50の底面(前記多孔質材料10に面した側)が脊椎5および周囲の筋肉および軟部組織に接触するよう、脊髄7から離れる方向へ巻き上げることもできる。前記柔軟なカバー50を脊髄7の下へ巻き込む場合は、この柔軟なカバー50の外面(脊椎5に面し、筋肉および軟部組織を囲む側)に接着剤52を塗布することにより、気密なシールの形成を促進できる。前記柔軟なカバー50を脊髄7から離れる方向へ巻き上げる場合は、この柔軟なカバー50の底面(脊椎5に面し、筋肉および軟部組織を囲む側)に接着剤52を塗布することにより、気密なシールを形成できる。
準大気圧は、前記カバー40、50と前記管20との協働作用により、当該カバー40、50の下に送達することができる。具体的には、図4のように、前記カバー40(または柔軟なカバー50)に減圧ポート43を含め、これに前記管20の前記遠端22を連結して、前記カバー40および脊髄7の間の前記空間48と前記管20との間に気体流通を提供することができる。あるいは、図5のように、前記カバー50(またはカバー40)に、前記管20と連通した通過口52を含めることにより、前記管20の前記遠端22が、前記カバー50および脊髄7の間の前記空間58内部に配置されるようにして、当該空間58および前記遠端22を気体流通可能にするようにできる。
前記カバー40、50は、さらに脊髄7周辺の皮下領域に閉鎖空間をつくって、準大気圧が保たれるよう作用することもできる。すなわち図4および図5に例示したように、前記カバー40、50は、その下の脊髄7周囲に密閉空間または領域48、58を提供することにより、脊髄7に適用される準大気圧の影響から、当該カバー40、50外部の組織を隔絶する作用をもたらす。これと対照的に、図2および図3で例示したようにカバーがない場合は、前記多孔質材料10および脊髄7に送達される準大気圧により、筋肉3、4などの周辺組織が前記管20および多孔質材料10へ向かって図2に示す矢印の方向に引き込まれる結果、図3に例示した組織構成になる。この場合、筋肉3、4などの伸長および/または移動した組織は、適用された準大気圧を筋肉4および脊髄7の間の領域に閉じ込める上で役立つことがある。また、前記カバー40、50は、前記多孔質材料10および縫合された皮膚2によりすでに得られる保護に加え、さらに外因性の感染および汚染から脊髄7を守る。同様に、当該カバー40、50は、脊髄膿瘍、膜炎、および脊髄組織の感染といった感染が脊髄7から広がらないよう脊髄の周辺組織をさらに保護する。
本発明の別の態様では、例として図1〜5に示した装置準大気圧を使って、損傷した脊髄組織を治療する方法も提供する。特に、この方法は、損傷した脊髄組織7に近接させて多孔質材料10を配置して、当該多孔質材料10の1若しくはそれ以上の細孔と前記損傷した脊髄組織7との間に気体流通を提供する工程を有することができる。損傷した脊髄組織7に近接した原位置(in situ)で前記多孔質材料10を密閉すると、損傷した脊髄組織7の周辺領域で準大気圧を保つことができる。この場合、筋肉3、4および皮下組織は、前記管20が皮膚2を貫通し、当該皮膚2が縫合され閉じた状態で、前記多孔質材料10の上方に弛緩状態で再接近させることができる。任意選択で、付加的な気密ドレッシング材を前記縫合部位の上から配置して、気密なシールの形成を促進することもできる。前記多孔質材料10は、損傷した脊髄組織7において準大気圧を発生するための減圧システム30と動作可能に連結でき、前記減圧システム30を作動させると、損傷した脊髄組織7において準大気圧を提供することができる。例えば、前記準大気圧は、大気圧より約25〜75mmHg低い圧力で維持することができる。この準大気圧は、損傷した脊髄組織7における浮腫を軽減する上で十分な時間、または脊髄液の漏出を制御するため、この脊髄組織7において維持することができる。また、この準大気圧は、損傷した脊髄組織7が治癒段階および細菌数減少段階に達して二次的な治療(皮膚フラップ、皮膚移植など)の受け入れ準備が整うまで、十分な時間、当該脊髄組織7で維持することができる。この方法は、少なくとも4時間、または多くの日数、使用することができる。この減圧治療の終了時には、縫合糸8を抜いて、皮膚2を再び切開する。次に、前記多孔質材料10を取り出して、前記皮膚2を再縫合することができる。
この方法には、損傷した脊髄組織7において準大気圧を維持するため、当該損傷した脊髄組織7の上からカバー40、50を配置する工程と、当該損傷した脊髄組織7に近接した組織を前記カバー40、50で密閉する工程とを含めることもできる。前記損傷した脊髄組織7周囲の組織を前記カバー40、50で密閉する工程は、当該損傷した脊髄組織7周囲の組織に当該カバー40、50を接着剤で接着させて密閉する工程を有することができる。前記カバー50は、粘着シート50の形態で提供でき、損傷した脊髄組織7の上から配置することができる。そのような場合、前記カバー50を密閉する工程には、損傷した脊髄組織7周囲の組織に前記粘着シート50を接着させて密閉し、前記シート50と前記損傷した脊髄組織7周囲の組織との間にシール(密閉部)を形成する工程を含めることができる。また、前記減圧システム30を前記多孔質材料10と動作可能に連結するは、前記減圧システム30を前記カバー40の前記減圧ポート42と連結する工程を有することができる。
実施例
ラットの脊髄損傷および準大気圧の適用
実験1
ラットの外傷急性期の脊髄に準大気圧が及ぼす効果を決定するため、一連の実験を行った。第1の動物プロトコールでは、250〜300グラムのSprague−Dawleyラットを取得し、脊髄外傷(挫傷)のモデルを開発して確認した。この外傷を生じ、回復を評価する手順は、Wrathallらの「ラットの脊髄外傷(挫傷):再現可能な段階的損傷群の生成」(Spinal Cord Contusion in the Rat:Production of Graded, Reproducible, Injury Groups)(Experimental Neurology 88、108−122(1985年)における脊髄外傷の説明に基づいたものとした。麻酔をかけたラットの脊髄を露出させ、ガラス管内で5cmの高さから10グラムの円柱形おもりを落下させることにより一貫した外傷を与える手術法が開発された。
前記ラットの半分は治療を行わない対照群で、残りの半分の外傷性領域には、準大気圧を4時間適用した(大気圧より25mmHg低圧)。ただし、前記損傷の度合いは、対照群のラットに著しい損傷を生じるものではなく(当該対照群ラットはすみやかに回復した)ため、治療されたラットを対照群のラットと比較することはできなかった。
実験2
より重度の傷害を脊髄に与える第2のプロトコールを開発した(10グラムのおもりをより高い位置、7.5cmから落下させる)。28匹の大型(300グラム)Sprague−Dawleyラットを一定期間にわたり得て、収容条件に順応させた。施術日、これらのラットに鎮痛剤を投与し、背中を剃毛および清拭して準備した。脊椎上の皮膚および皮下組織と、皮膚体幹筋および筋膜を背側正中切開し、その奥の背筋を露出させた。背側正中線両側の対の筋肉(僧帽筋および潜在的に広背筋)を背側正中線で分離し、両側へ剥離した。脊柱僧帽筋(spinotrapezius)および/または仙棘筋など、脊椎自体の骨構造に付着した深部の姿勢筋も、背側正中線で分離し、両側へ剥離した。これにより、棘突起および潜在的に横突起の一部を露出した。T7〜T9のレベルにおいて、棘突起と、連続した2つの脊椎間に延在する小さい横突棘筋とを除去し、脊髄の表面(硬膜)を露出させた。T8に椎弓切除術を行った。脊椎をT7およびT9で安定させ、Wrathallらの手順に基づき、10グラムのおもりを7.5cmの高さから落下させて、中程度の脊髄損傷を与えた。5匹のラットが、それぞれ初回の施術日に死亡し(3匹は対照群、2匹は減圧治療群)、本実験の早期では、対照群の1匹が実験2日目に死亡し、残り22匹となった。本実験の終了時までに、対照群および25mmHg減圧群に、それぞれ11匹ずつのラットを無作為に割り当てた。
対照群のラットについては一切治療を行わず、前記損傷を縫合して閉じた。減圧治療群のラットについては、ポリビニルアルコール減圧ドレッシング材(Vacuseal Plus、Polymedics社、ベルギー)を脊髄上に配置し、前記減圧管が切開部を貫通して延長した状態で、皮膚を縫合して閉じた。それから1時間遅らせて、前記減圧治療群の各ラットに、大気圧より25mmHg低い圧力(準大気圧)を4時間適用した。この治療終了時に、前記ラットに鎮痛剤を再投与し、減圧ドレッシング材を除去し、皮膚切開部をモノフィラメント縫合糸で再縫合した。
前記切開部については、毎日検査した。前記ラットについては、自己排尿能力の徴候の有無を検査した。排尿できなかった全ラットには、1日3回、8時間間隔で手作業で導尿した。前記ラットについては、自食作用(auto−cannibalism)の徴候の有無、褥創、および水分保持度(皮膚つまみ試験)を毎日検査した。これらのラットは、軟らかい木屑を敷いたケージに収容して、褥創が生じるおそれを最小限に抑えた。飼料は、摂食を容易にするため、ケージ底部に配置した。当該ラットについては、修正ターロブ(Tarlov)スコアリングシステムで各後肢を評価し、後肢の運動機能回復に関する検査を毎日行った(0=動いておらず、体重を支えていない、1=わずかに動いているが、体重は支えていない、2=頻繁に動いているが、体重は支えていない、3=体重を支えており、1〜2歩ステップ動作を行っている、4=障害を伴って歩行している、5=障害なく歩行している)。また、斜面(現位置を保てなくなり、平面上をスライドしてしまう角度)上で、当該ラット後肢の把持力強度を毎日試験した。施術から14日後に当該ラットを安楽死させ、各々の脊椎を除去して、組織学的に検査を行った。
本実験の結果は表1および表2のとおりで、「0」日目は施術日である。前記ラットのうち数匹に見られた損傷または障害はわずかで、おもりが落下した際に十分な損傷を受けなかった可能性がある(対照群ラット1、2、11、および治療群ラット3、9、10。表1および表2を参照)。2匹のラットは、重度損傷または完全損傷を呈し、回復しなかった(対照群ラット5、および治療群ラット2。表1および表2を参照)。そのため、合計では、対照群のラット7匹と、治療群のラット7匹とが、重度・完全損傷に至らない十分な損傷を受けたものと考えられた。
分析のため、ラットは、少なくとも4/4のスコアを達成した日に「回復した」と見なされた。前記7匹の対照群ラットのうち3匹は、施術後8日目になっても、少なくとも4/4のスコア(右脚/左脚で障害を伴って歩行する)まで回復しなかった(ラット3、6、7。表1)。残り4匹の対照群ラット(ラット4、8、9、10)のうち3匹は、4日目、6日目、および13日目に4/4のスコアに達し、1匹は7日目に4/5のスコアに達した。したがって、これら4匹の対照群ラットは、平均7.5±3.35日間で、少なくとも4/4のスコアに達した。前記治療群のラットについては、7匹すべて(ラット1、4、5、6、7、8、11)が、平均5.14±1.24日間で、少なくとも4/4のスコアに達した。そのため、25mmHgの減圧適用により、損傷した脊椎の機能的な回復率が向上したことは明白である(p=0.059)。
Figure 0005462175
Figure 0005462175
実験3
さらに重度の損傷を与え、回復不可能な(永続的)機能障害をもたらすよう、追加プロトコルを開発した。この外傷パラダイムは、W.M.Keck共同神経科学センター(W.M.Keck Center for Collaborative Neuroscience)で開発された脊髄損傷プロジェクト(The Spinal Cord Injury Project)技術に基づくもので、NYU脊髄外傷(挫傷)システム(NYU spinal cord contusion system)を使用する。これらのシステム(現在「MASCIS」と呼ばれている)はカスタム構築され、ラトガース大学生物学科(Biology Department at Rutgers University、W.M.Keck Center for Collaborative Neuroscience、米国ニュージャージー州Piscataway)を通じて市販されている。
上記では、おもりの重量に応じたラット実験を行ったが、本実験は、ラットの年齢に応じて行った。77日齢のLong Evans(hooded)ラットを用いて、損傷の重度を標準化した。施術日の1〜6日前の間に、これらラットの一部に鎮痛剤を投与して、ウェイクフォレスト大学医学部(Wake Forest University School of Medicine)の小動物MRIイメージング施設(Small Animal MRI Imaging Facility)へ運搬し、Bruker Biospin社製Horizontal Bore 7 Tesla小動物スキャナ(ドイツ、Ettlingen)を使ってT9〜T10のレベルで脊髄をスキャンした。次に、スキャンしたラットを暖房付きのケージで麻酔から回復させた。施術日、前記ラットに麻酔をかけ、その背部を剃毛して、脱毛クリームで除毛した。無菌技術を使い、T9〜T10レベルで椎弓切除術を行った。前記NYU脊髄外傷(挫傷)システムであるImpactorを使用し、10グラムのロッドを25mmの高さから脊髄T9〜T10に落下させて挫傷を与えた。対照群ラットの切開部は、縫合して閉じ、暖房付きのケージで回復させた。治療群のラットについては、ポリビニルアルコール減圧ドレッシング材(VersaFoam、Kinetic Concepts,Inc.、米国テキサス州サンアントニオ)を脊髄上に配置して皮膚を縫合して閉じ、25mmHgの減圧、すなわち大気圧より25mmHg低い圧力を8時間適用した。この後、前記治療済みのラットに鎮痛剤を再投与して切開部を開き、減圧ドレッシング材を除去し、当該切開部を再縫合して閉じた。前記ラットを施術後MRIにかけた場合は、前記脊髄損傷を与えた8時間後にスキャンを行った。
機能回復の評価は、上記W.M.Keck共同神経科学センターによる22点式の移動運動評価尺度であるBBBスケール(Basso,Beattie and Bresnahan(BBB)Locomotor Rating Scale)で行った(表3)。前記ラットについては、21日間監視したのち、致死量の二酸化炭素で安楽死させた。当該ラットには毎日導尿を行い、自食作用(auto−cannibalism)の徴候、褥創、皮膚の病変などの有無を監視した。自食作用の徴候を呈したラットは、すべて本試験から除外し、安楽死させた。褥創および皮膚の病変については、必要に応じ、ARP獣医職員との協議に基づき治療した。上記の配慮にもかかわらず、この実験過程では、一部のラットが死亡し、他のラットは他の問題で除外された。
Figure 0005462175
Figure 0005462175
硬膜が無傷のラット36匹が、永続的損傷に関するこれらの試験を完了し、分析された。減圧治療群は11匹のラットで開始し、1匹が5週目に、もう1匹が8週目に、尿路感染症および腎不全のため除外された。これにより、9匹の減圧治療群ラットが12週間の試験を完了した。対照群ラットとしては、27匹がこの試験を開始および完了した。これらの減圧治療群ラットは、損傷後3週間で、より優れた機能回復を呈した(p<0.072)。BBBスコア=12.818+/−1.401(n=11)減圧治療群対11.704+/−2.391(n=27)対照群。前記減圧治療群ラットは、損傷後4週間で、有意に優れた機能回復を呈した(p<0.001)。BBBスコア=13.625+/−1.303(n=11)減圧治療群対11.500+/−0.707(n=27)対照群(図6および図7)。前記減圧治療群ラットの回復は、横這い状態になり、前記対照群ラットの回復レベルは、前記減圧治療群ラットの回復レベルに徐々に近づいていった(図6および図7)(なお、一部のラットは3週間試験されたが(全般的に本試験の初期で)、12週間にわたり機能回復について観測されたものもあった)。
上記のBBB評価に加え、硬膜が無傷の2匹のラットについても、本実験の上記の手順を使って、損傷前後のMRIスキャンで脊髄の断面積(mm単位)の変化を分析した(減圧治療群ラットの場合、損傷後のスキャンは治療後に行った)。本分析のため用意された前記4匹のラットのうち、減圧治療した1匹だけが技術上または挫傷上の誤差がなく、使用することができた。前記対照群ラットのうち1匹については、脊髄挫傷システムのリリースピンをそのハウジングから引張ったとき、高さに関して軽微な誤差が生じた。その他の対照群ラットには、すべて有意な挫傷上の誤差が生じたため、脊髄の断面積に関する分析は除外した。おもりの落下高さを機械で記録した値は、前記減圧治療群ラットについて24.8mm、前記対照群ラットについて25.782mmであった。
図8を参照すると、前記対照群ラットでは、脊椎を下方へ(尾に向かって)スキャンするに伴い、断面積がわずかに増加した。これは、挫傷前スキャンおよび挫傷後スキャンのどちらでも明白であった。損傷部より上の部位および損傷部より下の部位の断面積は、挫傷前スキャンおよび挫傷後スキャンで、有意に異なっていない。損傷部より上の部位については、挫傷前スキャン平均が5.49mm+/−0.2(n=5)であるのに対し、挫傷後スキャン平均は5.32mm+/−0.23(n=4)である(p<0.211)(損傷部より下の部位については、挫傷前スキャン平均が6.81mm+/−0.25(n=3)であるのに対し、挫傷後スキャン平均は6.46mm+/−0.78(n=4)である(p<0.464))。ただし、前記対照群ラットの挫傷部位の断面積は、挫傷前と比べ、挫傷後有意に増大している(p<0.001)。すなわち、挫傷前の面積が5.63mm+/−0.24(n=5スキャン)であったのに対し、挫傷後の面積は6.43mm+/−0.32(n=4スキャン)となった。これは、脊髄直径の制限要因と考えられる骨が、この部位で除去されされていたため、硬膜の限界を超えて脊髄が腫脹したことによる可能性が最も高い。
前記対照群ラットと異なり、前記減圧治療群ラットでは、減圧治療後、損傷部位における脊髄平均直径の増加が見られない(図9)。この損傷レベル(部位)における挫傷前の平均面積は7.28mm+/−0.73(n=4スキャン)であるのに比べ、治療後の平均面積は7.03mm+/−0.99(n=4スキャン)である(p<0.73)。損傷部位において、挫傷前と治療後とで前記脊髄サイズが同様であったのは、硬膜内から液が除去されて脊髄の初期直径が維持されたことによる可能性が最も高い。
損傷部より上の領域において、挫傷前および治療後のスキャン結果は同様であった(有意に異ならない)。損傷部より上において、挫傷前の面積は7.79mm+/−0.64(n=3スキャン)であるのに比べ、治療後は8.33mm+/−1.11(n=5スキャン)である(p<0.48)。前記減圧治療群ラットの損傷部より下の部位のスキャンについては、治療後の脊髄断面積が、挫傷前の断面積より有意に増大している。すなわち、挫傷前の面積は7.61mm+/−0.43(n=4スキャン)であるのに比べ、治療後は10.76mm+/−0.35(n=4スキャン)となった(p<0.001)。この損傷部位より下での脊髄断面積の増加について考えられる説明は、静脈うっ血である。あるいは、減圧適用により脊髄周囲から脳脊髄液が能動的に吸引されたことにより、椎体内の脊柱管領域を充填するため脊髄が膨張した可能性もある。この膨張は、硬膜内圧を最小限に抑え、細胞生存率の維持に役立つよう作用する可能性がある。
以上に述べた本発明の利点等は、当業者であれば、本明細書の上記説明から明確に理解されるであろう。そのため、当業者であれば、本発明の範囲を逸脱しない範囲で上記の実施形態を変更または修正できることが理解されるであろう。従って、本発明は本明細書に説明した特定の実施形態に限定されず、添付の請求項に記載した本発明の要旨に含まれるすべての変更形態を含むよう意図されていると理解すべきである。

Claims (17)

  1. 損傷した脊髄組織を治療する機器であって、
    生体に導入可能な多孔質材料であって、当該生体に導入可能な多孔質材料の1若しくはそれ以上の細孔と前記治療すべき脊髄組織との間の気体流通を可能にするよう構成された細孔構造を有し、前記損傷した脊髄組織に隣接して配置される少なくとも1つの選択された表面において、当該生体に導入可能な多孔質材料の内部での脊髄組織の成長を防ぐ上で十分小さ細孔を有する、生体に導入可能な多孔質材料と、
    準大気圧を発生する減圧源であって、前記生体に導入可能な多孔質材料と気体流通可能に設けられ、前記治療すべき脊髄組織に前記準大気圧を分布させる、減圧源と
    を有する機器。
  2. 請求項1記載の機器において、前記生体に導入可能な多孔質材料は、オープンセル構造のコラーゲンを有するものである。
  3. 請求項1および2のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、ポリジオールクエン酸塩を有するものである。
  4. 請求項1〜3のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、ポリジオールクエン酸塩およびコラーゲンを有するものである。
  5. 請求項1〜4のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、エラスチン、ヒアルロン酸、またはアルギン酸塩、およびこれらの組み合わせを有するものである。
  6. 請求項1〜5のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、エレクトロスピニングした材料を有するものである。
  7. 請求項1〜6のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、成形した材料を有するものである。
  8. 請求項1〜7のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、印刷した材料を有するものである。
  9. 請求項1〜8のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、前記損傷した脊髄組織に近接して配置される、少なくとも1つの選択された表面を有し、前記選択された表面の細孔径は線維芽細胞および脊髄細胞のサイズより小さいものである。
  10. 請求項1〜9のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、その内部において、線維芽細胞および脊髄細胞より大きな細孔径を有するものである。
  11. 請求項1〜10のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、前記選択された表面以外の位置において、線維芽細胞および脊髄細胞より大きな細孔径を有するものである。
  12. 請求項1〜11のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料の細孔径は、アルブミンのサイズのタンパク質が通過できるようにする上で十分な大きさである。
  13. 請求項1〜12のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、準大気圧の伝達を防ぐよう密閉された少なくとも1つの表面を有するものである。
  14. 請求項1〜13のいずれか一項に記載の機器において、前記生体に導入可能な多孔質材料は、前記選択された表面以外の表面において、肉芽組織形成を促進する上で十分大きな細孔径を有するものである。
  15. 請求項1〜14のいずれか一項に記載の機器において、前記減圧源は、真空ポンプを有するものである。
  16. 請求項1〜15のいずれか一項に記載の機器において、この機器はカバーを有し、当該カバーは、前記損傷した脊髄組織を覆い、当該カバー下の当該損傷した脊髄組織において準大気圧を保つよう構成されているものである。
  17. 請求項16記載の機器において、前記カバーは、粘着シートを有する。
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JP2011500163A (ja) 2011-01-06
IL204825A (en) 2014-04-30
KR101600041B1 (ko) 2016-03-03
US20090187259A1 (en) 2009-07-23
US20200384168A1 (en) 2020-12-10
KR20100100798A (ko) 2010-09-15
CN101896140A (zh) 2010-11-24

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