KR0158669B1 - 투입된 원위치에서 형성되는 생분해성 이식조직 - Google Patents

투입된 원위치에서 형성되는 생분해성 이식조직 Download PDF

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KR0158669B1
KR0158669B1 KR1019900701183A KR900701183A KR0158669B1 KR 0158669 B1 KR0158669 B1 KR 0158669B1 KR 1019900701183 A KR1019900701183 A KR 1019900701183A KR 900701183 A KR900701183 A KR 900701183A KR 0158669 B1 KR0158669 B1 KR 0158669B1
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South Korea
Prior art keywords
polymer
drug
biodegradable
solvent
days
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KR1019900701183A
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KR920700017A (ko
Inventor
엘. 둔 라챠드
피이. 인글리쉬 제임스
알. 카우사 도날드
피이. 밴더빌트 데이비드
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폴 제이. 샤벨
아트릭스 러보러토리스 인코포레이티드
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Priority to KR1019980702530A priority Critical patent/KR0158670B1/ko
Publication of KR920700017A publication Critical patent/KR920700017A/ko
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract

내용없음

Description

[발명의 명칭]
투입된 원위치에서 형성되는 생분해성 이식조직
[발명의 상세한 설명]
[기술분야]
본 발명은 생분해성 중합체를 제조하기 위한 방법 및 조성물에 관한 것으로서, 보다 상세하게는 그러한 중합체를 주사될 수 있고 투입된 원위치에서 형성되며 고형인 생분해성 이식조직을 제공하는데 사용되는 방법에 관한 것이다.
[배경기술]
생분해성 중합체는 수년간 봉합재, 외과용 클립, 스태플, 이식조직 및 약물운반시스템 등 의약용도에 이용되어 왔다. 이러한 생분해성 중합체는 대부분 클리콜리드, 락티드, ε-카프로락톤 및 그의 공중합체를 기제로 한 열가소성 물질로, 그 대표적인 예로서는 Schmitt의 미합중국 특허 제3,297,033호에 설명되어 있는 폴리글리콜리드 봉합재와, Schneider의 미합중국 특허 제3,636,956호에 설명되어 있는 폴리(L-락티드-코-글리콜리드) 봉합재, Kaplan등의 미합중국 특허 4,523,591호에 설명되어 있는 폴리(L-락티드-코-글리콜리드) 외과용 클립과 스태플, 및 Boswell등의 미합중국 특허 제3,773,919호와 Yolles의 미합중국 특허 제3,887,699호, Schmitt의 미합중국 특허 제4,155,992호, Pitt등의 미합중국 특허 제4,379,138호, Shalaby등의 미합중국 특허 제4,130,639호 및 제4,186,189호에 설명되어 있는 약물-운반시스템 등이 있다.
상기 특허들에 설명되어 있는 생분해성 중합체는 모두가 열가소성 물질로서, 가열하여 섬유, 클립, 스태플, 핀, 필름 등과 같은 다양한 모양으로 형성될 수 있다. 이들 중합체는 융점이상의 온도로 가열되었을 때만이 액체가 되며, 정상조건에서 이용되는 동안에는 고체로 존재한다.
열경화되는 생분해성 중합체 또한 의약용도에 이용되어 왔다. 이들 중합체는 가교결합반응에 의해 형성되어, 고온에서도 용융되지 않거나 유동될 수 있는 액체를 형성하지 않는 고분자량의 물질이 된다. 이들 물질의 대표적인 예로는, Hostettler의 미합중국 특허 제2,933,477호 및 Hostettler등의 미합중국 특허 제3,186,971호에 설명되어 있는 가교결합된 폴리우레탄이 있으며, ε-카프로락톤과 L-락티드 또는 DL-락티드를 기제로 하고 페록시드 개시제를 통해 가교결합된 공중합체가 Sinclair의 미합중국 특허 제4,045,418호 및 제4,057,537호에 설명되어 있고, Pitt 등의 미합중국 특허 제4,379,138호에는 비스락톤을 단량체 원료로 조합하여 제조되어진 가교결합된 카프로락톤 공중합체가 설명되어 있다. 또한, Pitt 등의 J. Polym. Sci.:Part A:Poly Chem. 25:955-966; 1987에 설명된 바에 따르면, 트리히드록시-관능의 ε-카프로락톤과 ε-발레로락톤의 공중합체를 디이소시아네이트로 가교결합시켜서 생분해성 중합체를 제공하였다. 이들 중합체 역시 가교결합되고 경화되었을 때 교체로 존재한다.
상기 2부류의 생분해성 중합체는 많은 생체의약 용도에 유용하게 사용되어 왔으나, 인간, 포유류, 조류, 어류 및 파충류의 체내로 정의되는 체내에 이용되는 데에는 일부 제한이 따랐다. 즉, 이들 중합체는 고형이기 때문에 이들을 이용할 때에는 항상 먼저 체외에서 중합체 구조물을 형성한 후에 그러한 고형의 구조물을 체내로 삽입해야만 하였다. 예를 들면, 봉합재, 클립 및 스태플은 모두 사용하기 이전에 열가소성의 생분해성 중합체로부터 형성된다. 이들은 체내에 삽입되었을 때 유동되어 그들을 가장 필요로 하는 공극이나 강(腔)을 채우기 보다는 그들의 원래 형태를 유지한다.
이와 마찬가지로, 상기와 같은 생분해성 중합체를 이용하는 약물-운반 시스템도 체외에서 형성되어져야만 한다. 이 경우, 약물을 중합체에 조합하여 그 혼합물을 이식용의 실린더, 디스크 또는 섬유와 같은 임의의 형태로 성형한다.
그러한 고형의 이식조직과 약물-운반 시스템은 절개를 통해서만이 체내로 삽입될 수 있다. 이러한 절개부위는 종종 의료상 요구되는 것보다 넓어질 수 있는데, 이는 환자가 이식조직이나 약물운반시스템을 사용하는 것을 꺼리게 한다.
절개를 피하기 위해서는, 이들 중합체를 소립자, 미세구, 스피어, 마이크로캡슐 등으로 만들어 주사하는 방법밖에는 없다. 이들은 체내로 분비될 수 있는 약물을 포함하거나 포함하지 않을 수 있다. 이들 소립자들은 주사기를 통해 체내로 주사할 수는 있지만, 생분해성 이식조직으로서의 요건은 항상 만족시키지 못한다. 즉, 이들은 입자이기 때문에, 연속적인 필름이나 인공조직으로서 요구되는 구조적 통합성을 갖는 고형의 이식조직을 형성할 수 없으며, 이들 소립자나 미세구 또는 마이크로캡슐을 구강, 치은낭, 안구 또는 초막과 같이 유체의 흐름이 있는 임의의 체강에 삽입할 경우에는 그들의 작은 크기와 불연속적인 성질 때문에 거의 유지되지 못한다. 또한, 상기 중합체로부터 제조되며 체내로 분비되어질 약물을 함유하는 미세구 또는 마이크로캡슐은 때때로 대량 생산하기 어렵고, 그들의 저장 및 주사특성에도 문제가 있다. 더우기, 마이크로캡슐 또는 소립자 시스템은 광대한 외과적인 처치를 하기 전에는 그들의 회수가 어렵다는데 가장 큰 단점이 있는 바, 주사 후 부작용이 있을 경우에 이들은 고형의 이식조직에 비해 체내로부터 제거하기가 매우 어렵다.
따라서, 상기 문제점이 극복된 생분해성 중합체 구조를 제공하는 방법 및 조성물이 요구되었다.
또한, 인공기관 및/또는 조절성 운반시스템으로 이용될 수 있는 것으로서 주사가능하며 투입된 위치에서 형성되고 고형인 생분해성 이식조직을 제공하는 방법과 조성물이 요구되었다.
더우기, 연질 및 경질 조직모두에 사용될 수 있도록 부드러운 것으로부터 딱딱한 것에 이르기까지의 넓은 범위의 성질을 갖는 이식조직을 제공할 수 있는 방법 및 조성물이 요구되었다.
[발명의 개시]
본 발명은 액체상태로, 예컨대 주사기 또는 바늘을 통해 투여되며 투여된 후 단시간 내에 응고 및 경화되어 고형이 될 수 있는, 보결(補缺) 이식조직 및 조절성 분비, 약물-운반 시스템에 사용되는 생분해성 중합체의 제조와 그의 사용방법에 관한 것이다. 이식조직은 열경화성 및 열가소성의 2가지 형태의 중합체 시스템으로 이루어진 생분해성 중합체 및 공중합체로 만들어지기 때문에 생분해성이다.
열가소성 시스템은, 고형이며 직쇄인 생분해성 중합체 또는 공중합체를 비독성이며 물과 혼화될 수 있는 용매에 용해시켜서 액상의 용액을 형성함으로써 제공된다. 이 중합체 용액이 수분이 충분히 존재하는 체내에 투입되었을 때, 용매는 중합체로부터 소산 및 확산되고 남아 있는 중합체는 고형의 구조로 응고 및 고화된다. 이들 용액은 근육 또는 지방과 같은 연질의 조직이나, 벼와 같은 경질 조직, 치근막, 구강, 질, 직강, 비강과 같은 강, 혹은 치은낭, 결막과 같은 망상공동 등을 포함한 체내의 어디에나 투입될 수 있다. 약물-운반 시스템의 경우, 생물학적 활성 성분을 그가 용해될 수 있는 중합체 용액에 첨가하여 균질의 용액을 형성하거나 약물을 중합체 용액에 분산시켜 현탁액 또는 분산액을 형성함으로써 제공된다. 이러한 중합체 용액이 체액이나 물에 노출되면, 중합체-약물 혼합물로부터 용매가 소산되고 중합체가 응고되면서 물이 혼합물로 확산되게 되며, 이로써 이식조직이 고화되면서 약물이 중합체 매트릭스에 싸여 포괄되거나 마이크로캡슐화된다. 그후, 약물은 약물이 중합체 매트릭스로부터 확산 및 용해되는 일반적인 과정에 따라 분비된다.
또한, 본 발명의 또 다른 구현에는, 생분해될 수 있으며 투입된 원위치에서 형성 및 경화될 수 있는 가교결합 가능한 중합체를 합성시킴으로써 열경화성 시스템을 제공한다. 그러한 열경화성 시스템은 용매를 포함하지 않으며 반응성이고 액상이며, 올리고머 수준의 중합체로 이루어진 것으로서 투입위치에서 경화되어 고형을 형성하며, 일반적으로는 경화촉매가 첨가된다.
열경화성 시스템에 이용되는 다관능성 중합체는 먼저 DL-락티드 또는 ε-카프로락톤을 다관능성 폴리올을 개시제 및 촉매를 이용하여 공중합 반응시켜서 폴리올-말단 예비중합체를 형성함으로써 합성된다. 그 다음, 폴리올-말단 예비중합체는, 바람직하게는 Schotten-Baumann방법에 의해 알코올 말단을 아크릴로일 클로라이드로 아크릴화시키는 반응, 즉 아크릴 할라이드를 알코올과 반응시키는 것에 의해 아크릴산 에스테르-말단의 예비중합체로 전환된다. 아크릴산 에스테르 예비중합체는 그 밖에 다양한 방법에 의해서도 합성될 수 있는 바, 카복실산(즉, 아크릴 또는 메트아크릴산)과 알코올과의 반응, 카복실산 에스테르(즉, 메틸아크릴레이트 또는 메틸메트아크릴레이트)와 알코올과의 에스테르전이반응, 및 이소시아네이토알킬아크릴레이트(즉, 이소시아네이토에틸 메트아크릴레이트)와 알코올과의 반응에 의해 합성될 수 있다.
액상의 아크릴산-말단 예비중합체는, 바람직하게는 벤조일 페록시드 또는 아조비스이소부티로니트릴을 첨가하여 보다 고화된 구조로 경화시킬 수 있다. 따라서, 이들 가교결합 가능한 중합체를 이용하는 이식조직의 경우, 액상의 아크릴산-종료 예비중합체를 체내로 주사하기 직전에 촉매를 첨가시키게 되면, 충분한 분자량이 얻어질 때까지 가교결합반응이 진행되어 중합체가 고화되게 될 것이다. 주사 후 액상의 예비중합체는 투입하고자 하는 위치의 강 또는 공간으로 유동하며 고화될 때 형태를 갖게될 것이다. 이러한 시스템을 이용하여 약물을 운반하는 경우, 생물학적 활성성분은 액상의 중합체 시스템이 촉매화되지 않은 상태에서 첨가한다.
열가소성 및 열경화성 시스템 모두 액상으로 이용하는데 있어서의 잇점을 갖는다. 예컨대, 중합체가 액상을 유지하는 동안 주사기 및 바늘을 통해 체내로 주사될 수 있으며, 그 위치에서 잔류되어 고형의 생분해성 이식조직을 형성할 수 있다. 따라서, 절개가 불필요하며 이식조직은 그 강의 형태를 취하게 된다. 더우기, 주사전에 액체에 생물학적 활성성분을 첨가하게 되면 약물-운반 부형제가 제공될 수 있으며, 이렇게 형성된 이식조직은 체내에서 활성성분을 분비하면서 생분해된다. 여기서, 생물학적 활성성분은 체내에 효과를 나타낼 수 있는 약물 또는 기타 다른 물질을 의미한다.
그러므로, 본 발명의 목적은, 생분해성 중합체를 형성하는 방법 및 조성물을 제공하는데 있다.
또한, 본 발명의 목적은 주사될 수 있으며 투입된 원위치에서 형성되고 고형인 생분해성 이식조직을 형성하는데 유용한 중합체를 제공하는데 있다.
또한, 본 발명의 목적은 생물학적 활성 물질의 분비가 조절되는 운반 시스템으로 이용될 수 있는 이식조직을 제공하는데 있다.
그리고, 본 발명의 목적은 연질 및 경질 조직 모두에 사용될 수 있도록 연질이며 탄력성있는 것으로부터 경질이고 딱딱한 것에 이르기까지 광범위한 성질의 이식조직을 제공하는데 있다.
[도면의 간단한 설명]
제1도는 아크릴레이트-말단 예비중합체의 합성과 그에 이은 자유라디칼의 가교결합을 도시한 것이고,
제2도는 디올로 개시된 ε-카프로락톤과 L-락티드와의 공중합 반응과 그로 인한 랜덤 공중합체의 구조를 도시한 것이며,
표 1은 합성된 2관능성의 PLC 예비중합체들을 요약한 것이고,
표 2는 합성된 아크릴산 에스테르 말단의 예비중합체들을 요약한 것이며,
표 3은 경화연구를 요약한 것이다.
[발명의 실시하기 위한 최선의 형태]
본 발명은 투입된 원위치에서 형성되는 생분해성 이식조직과 그를 제조하는 방법에 관한 것이다. 또한, 본 발명은 체내에 주사되어 투입된 원위치에서 고화되며 생물학적 활성성분이 조절된 속도로 분비될 수 있는 액상의 생분해성 중합체로 이루어진 운반시스템에 관한 것이다. 생분해성 중합체 시스템에는, 생적합성 용매에 용해되어 있는 열가소성 중합체와 용매없이 액상으로 존재하는 열경화성 중합체로서 구분되는 2가지 형태가 있다.
A. 열가소성 시스템
열가소성 시스템은 고형이며 직쇄의 생분해성 중합체를 생적합성 용매에 용해시켜 액체를 형성함으로써 제공되며, 이들은 주사기 및 바늘을 통해 투여될 수 있다. 여기에 적용될 수 있는 중합체로는, 예컨대, 폴리락티드, 폴리글리콜리드, 폴리카프로락톤, 폴리디옥사논, 폴리카보네이트, 폴리히드록시부티레이트, 폴리알킬렌록살레이트, 폴리안하이드라이드, 폴리아미드, 폴리에스테르아미드, 폴리우레탄, 폴리아세테이트, 폴리케탈, 폴리오르토카보네이트, 폴리포스파젠, 폴리히드록시발러레이트, 폴리알킬렌석시네이트, 폴리(말산), 폴리(아미노산), 폴리비닐피롤리돈, 폴리에틸렌 글리콜, 폴리히드록시 셀룰로스, 키틴, 키토산 및 폴리오르토 에스테르와, 그의 공중합체, 삼량체, 및 그의 조합물 또는 혼합물 등이 있다. 이들중에서도 결정화도가 보다 낮고 보다 소수성인 중합체가 바람직한데, 이는 이러한 중합체 및 공중합체가 고도의 수소-결합을 갖는 폴리글리콜리드 및 키틴 등의 고결정성 중합체에 비해 생적합성 용매에 보다 잘 용해되기 때문이다. 적절한 용해 변수를 갖는 바람직한 물질로는 보다 무정형이어서 용해성이 우수한 폴리락티드, 폴리카프로락톤 및 이들과 글리콜리드와의 공중합체가 있다.
한편, 생분해성 중합체를 위한 용매는 비독성이며 물과 혼화될 수 있을 뿐만 아니라 생적합성인 것이 바람직하다. 독성을 갖는 용매는 생체내로 어떤 물질을 주사하는데에도 사용해서는 안된다. 또한 용매는 이식부위에서 조직의 자극 또는 괴사가 발생되지 않도록 생적합성을 갖아야만 한다. 그리고, 용매는 체내로 빠르게 분산되고 물이 중합체 용액으로 침투될 수 있어서 응고 및 고화가 일어날 수 있도록 물과 혼화될 수 있어야 한다. 그러한 용매의 예로는 N-메틸-2-피롤리돈, 2-피롤리돈, 에탄올, 프로필렌 글리콜, 아세톤, 에틸아세테이트, 메틸아세테이트, 메틸에틸케톤, 디메틸포름아미드, 디메틸설폭시드, 테트라히드로퓨란, 카프로락탐, 데실메틸설폭시드, 올레인산 및 1-도데실아자사이클로헵탄-2-온등이 있으며, 그들의 용매화 능력과 생적합성을 고려할 때 N-메틸-2-필로리돈, 2-피롤리돈, 디메틸설폭시드 및 아세톤이 바람직하다.
다양한 용매에서 생분해성 중합체의 용해성은 그의 결정성, 친수성, 수소결합 및 분자량에 따라 차이가 있을 것이다. 그러므로, 모든 생분해성 중합체가 동일한 용매에 용해되지는 않을 것인 바, 각 중합체 또는 공중합체에 따라 최적의 용매를 선택하여야 한다. 저분자량의 중합체는 고분자량의 중합체보다 일반적으로 용매에 쉽게 용해될 것이다. 따라서, 다양한 용매에 용해된 중합체의 농도는 중합체의 형태와 그 분자량에 따라 다를 것이다. 반대로, 고분자량의 중합체는 저분자량의 중합체에 비해 일반적으로 빠르게 응고 및 고화될 것이며, 또한 고분자량의 중합체는 저분자량의 중합체보다 높은 용액점도를 나타낼 것이다. 그러므로, 최적의 주사효과를 나타내기 위해서는, 용매중에서의 중합체의 분자량과 농도를 조절하여야 한다.
예컨대, 락트산을 축합시켜서 형성된 저분자량의 폴리락트산은 N-메틸-2-피롤리돈(NMP)에 용해시켜서 73중량%의 용액으로 만들어야, 23-게이지의 주사바늘을 통해 쉽게 유입시킬 수 있을 것이다. 반면, DL-락티드를 부가 중합반응시켜서 형성된 고분자량의 폴리(DL-락티드)(DL-PLA)는 NMP에 50중량%만 용해시켰을 때 상기와 동일한 점도를 얻을 수 있다. 이러한 고분자량의 중합체 용액은 물에 투입했을 때 즉시 응고되는 반면, 저분자량의 중합체 용액은 보다 농축되었다 할지라도 물에 투입되었을 때 매우 느린 속도로 응고된다.
느리게 응고되는 경향의 중합체는, 혼합용매를 사용함으로써 응고속도를 향상시킬 수 있다. 즉, 혼합용매중 하나의 액상성분은 중합체를 잘 용해시키는 것으로 하고 나머지 하나는 난용해성 또는 불용해성의 것으로 하며, 두 액상성분의 비율을 중합체를 용해시키되 생리환경에서 물과 같은 불용해성 용매가 극소량 증가하여도 중합체를 침전시키는 정도가 되게 한다. 그리고, 필수적으로 용매시스템은 물과 중합체 모두와 혼화될 수 있어야 한다. 그러한 2성분의 용매 시스템으로는 저분자량의 DL-PLA를 위한 것으로서 NMP와 에탄올을 이용한 것을 예로 들 수 있다. 이처럼, NMP/중합체 용액에 에탄올을 첨가하게 되면 응고속도가 매우 향상된다.
본 발명자들은, 때때로 고분자량 중합체가 매우 높은 농도로 함유된 용액의 경우 보다 희석된 용액에서 보다 느리게 응고 및 고화된다는 것을 발견하였다. 이는, 고농도의 중합체가 중합체 매트릭스내로부터 용매가 확산되는 것을 방지하여 결과적으로 중합체를 침전시킬 수 있도록 매트릭스 내로 물이 침투하는 것을 막게 되기 때문인 것으로 추측되는 바, 용매가 중합체 용액으로부터 확산되고 중합체내로 물이 침투되어 응고될 수 있는 적정농도로 하여야 한다.
열가소성 시스템의 기대되는 용도의 하나는, 중합체 용액을 주사기에 채워 바늘을 통해 체내로 주입하는 것이다. 중합체 용액이 투입된 후에 용매는 소산되고 잔류된 중합체는 고화되어 고형구조를 형성한다. 이때, 이식조직은 기계적인 힘에 의해 그 주위의 조직 또는 뼈에 부착될 것이며, 그 주위를 둘러싸고 있는 강(腔)형태를 취할 수 있다. 따라서, 생분해성 중합체 용액은 콜라겐 같이 피부하로 주사되어 조직을 형성하고 손상부위를 채울 수 있으며, 또한 화상과 같은 상처에 주사되어 반흔이 깊어지는 것을 막을 수 있다. 이러한 이식조직은, 콜라겐과는 달리, 선택된 중합체의 종류와 그 분자량에 따라 분해시간을 몇주로부터 몇 년에 이르기까지 다양하게 할 수 있다. 또한 주사될 수 있는 중합체 용액은, 히드록시아파타이트 플러그와 같은 다른 고형의 생분해성 이식조직을 뼈의 틈을 사이에 주입했을 경우에는, 뼈의 손상부위를 보완해 주거나 혹은 연속적인 매트릭스를 제공하는데 사용될 수 있다. 이들 주사될 수 있는 시스템은 그의 기계적 결합특성으로 인해 조직과 조직 또는 다른 이식조직을 접착시키거나 조직 및 인공기관을 캡슐로 싸는데 사용할 수 있다.
열가소성 시스템의 기대되는 또 다른 용도는 약물-운반 시스템을 제공하는 것이다. 이 경우, 주사전에 중합체 용액에 생체활성물질을 첨가한 후에 중합체/용매/활성물질의 혼합물을 체내로 주사한다. 이때 약물이 용매에 가용성이면 약물과 중합체와의 균질한 용액을 형성하여 이를 주사용할 수 있을 것이며, 약물이 용매에 잘 용해되지 않으면 약물이 중합체 용액중에 분산 또는 현탁된 현탁액 및 분산액을 체내로 주사할 수도 있다. 이러한 양자 모두에서, 용매는 소산되고 중합체는 고화되어 고형의 매트릭스내의 약물을 포괄하게 될 것이다. 약물은 이러한 고형의 이식조직으로부터 분비될 때 단일성 중합체 부품으로부터 약물을 분비하는데 있어서의 일반적인 과정에 따른다. 약물의 분비는 이식조직의 크기 및 형태와, 이식조직에 약물을 충전하는 방법, 약물 및 특정 중합체를 포함한 침투요인, 중합체의 분해 등에 영향을 받는다. 이 분야에 숙련된 자들은 운반시키고자 하는 생체활성물질에 따라 목적하는 분비속도 및 기간을 갖도록 상기 변수를 조정할 수 있을 것이다.
여기서 사용된 약물 또는 생체활성물질(생물학적 활성물질)이라는 용어는, 체내에서 국부적 또는 전신에 작용하는 생리학적 또는 약제학적으로 활성을 갖는 물질이면 모두가 포함된다. 주사될 수 있고 투입된 원위치에서 형성되는 고형의 이식조직 시스템에 사용되는 약물 및 생물학적 활성물질의 대표적인 예로는, 펩타이드제, 단백질제, 제감작제, 항원, 왁찐, 항감염제, 항생제, 살균제, 항알레르기제, 스테로이드성 소염제, 충혈제거제, 축동제, 항콜린제, 교감신경흥분제, 진정제, 혈압저하제, 향신경제, 배란제, 체액성제, 프로스타글란딘, 진통제, 진경제, 항말라리아제, 항히스타민제, 강심제, 비스테로이드성 소염제, 항파킨슨제, 혈압강하제, β-아드레날린 차단제, 영양제 및 벤조페난트리딘 알카로이드 등이 있다. 이 분야에 숙련된 자들에게는, 수용성 환경에서 분비될 수 있는 상기 이외의 약물 및 생물학적 활성물질도 목적하는 주사가능한 운반시스템에 이용될 수 있다. 또한, 다양한 형태의 약물 또는 생물학적 활성물질이 이용될 수 있는 바, 체내에 주사되었을 때 생물학적으로 활성화되는 비하전성 분자, 분자복합체, 염, 에스테르 등과 같은 형태도 포함된다. 주사가능하고 투입된 위치에서 고형이 되는 이식조직에 조합되는 약물 또는 생물학적 유효성분의 양은 목적하는 분비형태와 생물학적인 효과를 나타내는데 요구되는 약물의 농도 및 약물을 방출하여야 할 치료기간에 따라 결정된다. 중합체 용액에 조합되는 약물의 양의 상한선은 수용체 용액 또는 분산액의 점도가 주사바늘을 통해 주사될 수 있는 정도이면 제한이 없으며, 또한 운반 시스템에 조합되는 약물의 양의 하한선은 단순히 약물의 활성과 치료기간에 따른다.
상기 모든 경우에서, 주사될 수 있는 중합체 용액으로부터 형성된 고형의 이식조직은 체내에서 느리게 생분해되어 이들이 소멸되면서 천연조직이 성장 및 대체되도록 할 것이다. 그러므로, 연질 조직의 손상부위에 주사할 경우, 손상부를 채우고 골격을 제공하여 천연 콜라겐 조직이 성장되도록 할 것이며, 이러한 콜라겐 조직은 점차 생분해성 중합체를 대체하게 될 것이다. 뼈와 같은 경질의 조직에 사용될 경우, 생분해성 중합체는 새로운 골세포의 성장을 지지할 것이며, 이들 새로운 골세포는 점차 분해된 중합체를 대체하게 될 것이다. 약물-운반 시스템의 경우, 주사될 수 있는 시스템으로부터 형성된 고형의 이식조직은 그 매트릭스에 포함된 약물을 그 약물이 고갈될 때까지 조절된 속도로 분비할 것이다.
이때, 일부 약물의 경우 중합체를 약물이 완전히 분비된 후에 분해되도록 할 수 있으며, 펩티드나 단백질 등의 또 다른 약물의 경우에는 중합체에 비-확산약물이 체액에 노출될 때까지 분해된 후에 완전히 분비되도록 할 수 있다.
B. 열경화성 시스템
주사가능하며, 투입된 위치에서 형성되고 생분해성인 이식조직은 적당히 관능화된 생분해성 중합체를 가교결합시킴으로써 제조될 수도 있다. 열경화성 시스템은 반응성이고 액상이며, 올리고머 수준의 중합체로 이루어진 것으로, 경화되어 고체가 되며, 일반적으로 경화촉매가 첨가된다. 중합체로는 앞서 열가소성 시스템에서 설명한 생분해성 중합체중 어느 것이나 사용될 수 있으나, 이들 중합체 또는 공중합체중에서 저분자량의 올리고머는 액상이어야 하며 예비중합체의 말단에 관능기를 갖고 있어서 아크릴로일 클로라이드와 반응하여 아크릴산 에스테르 말단의 예비중합체를 형성할 수 있어야 하는 제한이 있다.
바람직한 생분해성 시스템은, 폴리(DL-락티드-코-카프로락톤) 또는 DL-PLC로부터 제조된 것이다. 이러한 물질로부터 제조된 저분자량의 중합체 또는 올리고머는 실온에서 유동될 수 있는 액상이다. 히드록시-말단의 PLC 예비중합체는 DL-락티드 또는 L-락티드와 ε-카프로락톤을 다관능성 폴리올 개시제 및 촉매로 공중합 반응시켜서 합성될 수 있다. 이러한 예비중합체를 제조하는데 유용한 촉매는 염기성 또는 중성 에스테르 호환(에스테르 전이반응)촉매가 바람직하며, 그러한 촉매로는 포름산, 아세트산, 라우르산, 스테아르산 및 벤조산과 같은 탄소원자수 18이상을 포함하는 카복실산의 금속에스테르가 일반적으로 사용되며, FDA 승인 및 효과를 고려할 때 옥토산주석(stannous octoate)과 염화제일주석이 특히 바람직하다.
2관능성 폴리에스테르가 요구되는 경우 에틸렌 글리콜과 같은 2관능성 쇄-개시제가 사용되며, 트리메틸올프로판과 같은 3관능성 개시제는 3관능성 중합체를 제조하는데 사용된다. 이들 쇄-개시제의 사용량은 그 결과로 얻고자 하는 중합체 또는 공중합체의 분자량에 따라 결정된다. 쇄-개시제가 고농도로 존재할 때 하나의 2관능성 개시제는 단지 하나의 중합체 쇄만을 개시하는 한편, 2관능성 개시제의 농도가 매우 낮을 경우에는 각 개시제는 2개의 중합체쇄를 개시시킬 수 있다. 어느 경우에나, 제1도에 나타낸 바와 같이 중합체는 히드록시기 말단을 갖는다. 이러한 예에서, 2관능성 개시제 분자당 단지 하나의 중합체 쇄만이 개시되는 것으로 추측되는데, 이러한 추측은 예비중합체에 대한 분자량의 이론 값을 산출할 수 있도록 한다.
합성된 2관능성 PLC 예비중합체의 목록을 다음의 표 1에 나타내었다. 이때 그 관능성 PLC 예비중합체의 합성을 다음과 같이 수행하였다. 적당량의 DL-락티드, ε-카프로락톤 및 에틸렌 글리콜을 질소하의 플라스크중에서 조합하고 유조에서 155℃로 가열하여 단량체를 용융 훈련한 다음, 0.03 내지 0.05중량%의 SnCl2를 첨가하여 촉매시켜서 공중합반응을 밤새도록 수행하였다. 예비중합체의 히드록실 수는 표준 적정법에 의해 결정하였으며, 액상 예비중합체의 가드너-홀트 점도는 ASTM D 1545 방법에 따라 측정하였다. 최고 분자량의 예비중합체(MW=5000)는 실온에서도 고형이었으므로 그의 가드너 홀트 점도를 측정할 수 없었다.
디올 예비중합체는, 제2도에 나타낸 바와 같이 Schotten-Baumann 조건하에서 아크릴로일 클로라이드와 반응시켜서 아크릴산 에스테르-말단 예비중합체로 전환시키며, 이를 다음의 표 2에 요약하였다. 디올 예비중합체를 아크릴산 에스테르-말단의 예비중합체로 전환시키기 위하여 그 밖의 다른 방법도 사용될 수 있다.
TMF 및 디클로로메탄 모두가 아크릴화 반응의 용매로서 유용하다. TMF를 용매로 사용하였을 때 몇몇 문제가 있는 바, 반응의 부생성물로서 형성된 트리에틸아민 히드로클로라이드는 미세하게 분배되어 반응혼합물을 여과시키는 것에 의해서는 효과적으로 제거시킬 수 없다. 트리에틸아민 히드로클로라이드(Et3N·HCl)는 아크릴류의 중합반응을 유발한다고 보고된 바 있다(미합중국 특허 제4,405,798). 몇몇의 경우, Et3N·HCl을 전부 제거하는데 실패하였을 때 아크릴산 에스테르-말단의 예비중합체는 보다 일찍 겔화되었다. 따라서 Et3N·HCl 전부를 효과적으로 제거하기 위해서는, 예비중합체를 물로 추출하는 것이 필요하다. 반응을 THF에서 수행하는 경우에는, 먼저 THF를 진공에서 증발시키고 CH2Cl2층을 물로 추출하는데, 때때로 이렇게 추출하는 동안 안정한 유화액이 되었다. 아크릴화 반응은 이후에 THF 대신 CH2Cl2에서 수행하였다. 본 발명자들은 이러한 용매를 사용하면 반응혼합물로부터 Et3N·HCl을 여과해 내기가 보다 용이함을 발견하였으며, 여과 후 유기 분획을 물로 직접 추출할 수 있었다.
디올 및 아크릴산 예비중합체 모두를 IR 및1H NMR 스펙트로스코피하여 시험하였다. 디올 예비중합체에 대한 IR 스펙트럼의 특징은 약 3510cm-1에서 돌출된 O-H 스트레치를 갖는데 있다. 아크릴화 반응에서, O-H 스트레치의 정도는 현저히 감소되며, 약 1640cm-1에서 새로운 흡수가 나타났는데, 이 새로운 흡수는 아크릴기와 관련된 C-C 스트레치로 인한 것이다. 마찬가지로, 아크릴 에스테르기의 존재는1H NMR 스펙트라에, 5.9 내지 6.9ppm의 범위에서 비닐 프로톤에 대한 특징적인 공명을 나타내었다.
그런 다음, 아크릴 예비중합체와 다음 예비중합체를 표 3에 요약한 바와 같이 경화시켰다. 예비중합체를 경화시키는 일반적인 방법은 다음과 같은 바, 작은 비이커에 담겨 있는 5.0g의 아크릴산 예비중합체에 약 1㎖의 CH2Cl2에 벤조일페록시드(BP)를 용해시켜서 된 용액을 첨가시켰다. 일부의 경우, 예비중합체를 BP용액에 투입하기 전에 부형제 또는 부가적인 아크릴 단량체를 첨가시켰다. 이 혼합물을 교반시킨 후 페리접시에 붇고, 이 접시를 예열된 진공오븐에서 경화시켰다. 샘플의 일부는 진공이 아닌 공기중에서 경화시켰다. 이들 샘플을 다음의 표 3에 나타내었다.
이러한 열경화성 시스템은 생분해성 이식조직이 요구되는 어느 곳에나 이용될 수 있다. 예컨대, 예비중합체는 경화제를 첨가한 후 짧은 시간동안 액상으로 존재하기 때문에, 액상 예비중합체/경화제 혼합물은 주사기를 통해 체내에 주사될 수 있다. 그런 다음, 혼합물은 투입된 원위치에서 교화되므로 이식조직을 제공하기 위해 절개할 필요가 없다. 또한, 약물-운반 시스템은 예비중합체를 주사하기 전에 생물학적 활성성분을 첨가함으로써 제공될 수 있다. 이때, 시스템은 투입된 원위치에서 경화되어 고형이 될 것이며, 결국 생분해되어 약물을 점차 분비하게 될 것이다.
[실시예에 대한 상세한 설명]
본 발명을 다음의 실시예를 통해 예시하였다. 다음의 실시예는 본 발명의 범위를 한정하는 것이 아닌 바 이들 이외의 다른 동등한 구현예가 존재할 수 있음이 본 명세서와 도면 및 첨부된 청구범위에 의해 명백해질 것이다.
[실시예 1]
폴리(DL-락트산)은 락트산을 간단히 다중축합반응시켜 제조하였다. 촉매는 사용하지 않았으며 반응시간을 다양하게 하여 이론상 서로 다른 분자량을 갖는 중합체들을 합성하였다. 이러한 고분자들을 DL-PLA 올리고머로 표시하였다. 다량의 고형 올리고머를 NMP에 용해시 중합체와 용매의 비가 68:32가 되게 하였다. 살균물 활성, 특히 충치균에 대해 활성을 갖는 벤조페난트리딘 알카로이드, SaCl(생귀나린 클로라이드)을 중합체 용액에 첨가하여 총혼합액중에 약물이 2중량% 함유된 분산액이 되게 하였다. 분산액과 중합체 용액을 바늘이 없는 살균처리한 주사기로 투석튜브(직경 11.5mm)에 주사한 후, 약물과 중합체의 혼합 용액의 손실을 막기 위해 6인치 길이의 투석튜브 끝을 묶고 주사된 물질이 담겨진 튜브를 37℃를 유지하면서 pH 7의 소렌슨 완충액에서 방치하였다. 수용체 용액에 액침하였을 때, 약물/중합체 덩어리는 단단하게 응고되었으나 약물은 수용체 용액에서 주황색을 나타내면서 중합체로부터 분리되었다. 투석튜브에 주사된 용액의 양은 약 250㎖ 또는 고체로 100㎎정도로 하였다. 투석튜브로는 분자차단 계수가 3,500인 것을 선택하였다. 이러한 분자차단계수의 것을 사용하게 되면 중합체에서 분비된 SaCl은 튜브의 벽을 통해서 쉽게 확산되는 반면, 고체성 중합체는 잔류되었다. 약물/중합체 매트릭스를 포함하고 있는 투석튜브를 자주 옮겨서 새로운 수용체 용액에 담아 두었다. 그런 다음, 분비된 약물을 포함하는 사용되었던 수용체 용액을 pH 2.76으로 산성화시켜서, 모든 분비된 약물이 약물의 이미늄 이온형태로 전환시키고, 약물의 농도를 237㎚ 파장에서의 UV 흡광도로 결정하였다. 분비된 약물의 누적질량과 누적분율을 계산하여 시간에 대한 함수로 표시하였다. 첫날내에는 약 60%의 약물이 분비되었으며 2일 후에는 72%, 5일 후에는 85%, 9일 후에는 90%, 14일 후에는 97%가 분비되었다.
[실시예 2]
생귀나린의 에탄올 에스더인 SaEt(에톡시디히드로생귀나린)를 상기 실시예 1에서와 같은 DL-PLA 올리고머/NMP 용액에 첨가하였다. SaEt는 중합체 용액에 용해되어 약물과 중합체의 균질용액이 되었다. 수용체 용액에 약 250㎕의 용액을 첨가하고 상기 실시예 1에서와 같은 방법으로 분비된 약물을 정량하였다. SaEt이 물에 대한 용해도가 낮다는 점에서 예측될 수 있는 바와 같이 SaEt의 분비는 SaCl에서 보다 낮았다. 첫날에는 거의 45%가 분비되었고, 2일 후에는 52%, 5일 후에는 60%, 9일 후에는 70%, 14일 후에는 80%가 유지되었다.
[실시예 3]
라우릴 알코올을 개시제로 하고 SnCl을 촉매로 하여 DL-락티드를 개환 중합반응시켜서 0.08dL/g의 고유점도와 2,000의 이론 분자량을 갖는 폴리(DL-락티드)를 제조하였다. 그런 다음, 이 중합체를 NMP에 40중량%의 중합체 용액이 되게 하고, SaCl을 NMP에 상기 중합체가 용해되어 있는 용액에 1.5%가 되게 분산시키고 분비속도를 상기 실시예 1의 방법으로 정량하였다. 이러한 분자량이 보다 큰 중합체로 부터의 약물의 분비속도는 DL-PLA 올리고머에서 보다 늦는 바, 첫날에는 약 32%가 분비되었고, 2일 후에는 40%, 5일 후에는 45%, 15일 후에는 50%가 분비되었다.
[실시예 4]
상기 실시예 3에서와 동일한 NMP에 DL-PLA 용해시켜서 된 동일 중합체 용액에 SaEt를 첨가하여 약물이 1.5중량%로 함유된 균일한 약물 용액을 얻었다. 약물의 분비속도를 상기 실시예 1에서와 동일한 방법으로 측정한 결과, DL-PLA 올리고머에서 보다 SaEt의 분비가 훨씬 늦었는 바, 첫날에는 약 8%, 2일 후에는 14%, 5일 후에는 20%, 9일 후에는 23%, 14일 후에는 28%가 분비되었다.
[실시예 5]
충전된 약물이 중합체 용액으로부터 약물을 분비하는데 미치는 효과를 40중량% DL-PLA 올리고머를 함유하는 NMP에 SaCl를 첨가함으로써 입증하였다. 약물을 중합체 용액에 2,7,14중량%로 분산시켰다. 상기 실시예 1과 같은 방법을 사용하여 이들 제형으로 부터의 약물의 분비를 측정한 결과 확산분비하는 매트릭스 운반시스템에 충전된 약물 양이 클수록 분비의 분율속도가 낮은 것으로 나타났다. 2%가 충전된 제형에서는 1일 후에는 65%, 2일 후에는 75%, 5일 후에는 88%가 분비되었고, 7%가 충전된 제형에서는 1일 후에는 48% 2일 후에 52%, 5일 후에는 58%가 분비되었으며, 14%가 충전된 제형에서는 1일 후에 38%, 2일 후에는 43%, 5일 후에는 49%가 분비되었다.
[실시예 6]
개시제로서 라우릴 알코올을 사용하고 SaCl를 촉매로서 사용하여 글리코리드와 DL-락티드 혼합액을 개환중합반응시켜서 폴리(DL-락트디-코-글리코리드)를 제조하였다. 이때, 두 단량체의 비율은 최종공중합체(DL-PLG)에서 핵자기 공명분광계로 정량하였을 때 두 단중합체의 비가 50:50이 되도록 조정하였고, 또한 개시제로는 1500달톤의 이론 분자량을 갖는 중합체가 되도록 조정되었다. 그런 다음, 얻어진 공중합체를 NMP에 용해하여 70중량%의 중합체 용액을 얻었다. SaCl을 상기 용액에 첨가하여 약물이 중합체용액에, 2중량%가 함유되도록 하였다.
이 제형으로 부터의 약물의 분비속도를 상기 실시예 1에서와 동일한 방법으로 정량한 결과, 이 공중합체는 DL-PLA 올리고머나 분자량 2000의 DL-PLA에서 보다 분비속도가 낮았는 바, 2일 후에는 약 7%, 5일 후에는 10%, 7일 후에는 12%, 14일 후에는 16%의 약물이 분비되었다.
[실시예 7]
상기 실시예 6에서와 동일한 NMP에 DL-PLG를 용해시켜서 된 중합체 용액에 SaEt를 첨가하여 2중량%의 약물 용액을 얻었다. 이 제형으로 부터의 약물의 분리비속도를 앞에서 언급한 방법으로 정량한 결과, 이 제형으로 부터의 SaEt의 분비속도는 상기 실시예 6에서 설명한 SaCl 분비속도와 동일하였다.
[실시예 8]
상기 실시예 6에서와 동일한 NMP에는 DL-PLG를 용해시켜서 된 용액에 유리염기형의 테트라사이클린(TCB)을 첨가하였다. 약물을 중합체 용액에 완전히 용해하여 2.4중량%의 약물 용액이 되게 하였다. 이 제형으로 부터의 약물의 분비속도를 수용체 용액을 pH 2.76으로 산성화하시키는 것을 제외하고 상기 실시예 1에서와 유사한 방법으로 정량하고, TCB의 농도를 약물에 대한 적절한 파장에서 UV 흡수로 정량하였다. 이 제형에서 TCB의 분비는 매우 선형적이며 동일한 공중합체에서의 SaEt나 SaCl의 분비 보다 더 높은 속도를 내었는 바, 1일 후에는 약 44%의 약물이 분비되었고, 2일 후에는 54%, 5일 후에는 68%, 6일 후에는 78%, 7일 후에는 80%, 9일 후에는 87%, 12일 후에는 96%, 14일 후에는 거의 100%가 분비되었다.
[실시예 9]
상기 실시예 6에서와 동일한 NMP에 DL-PLG를 용해시켜서 된 용액에 테트라사이클린 염산염(TCH)을 첨가하였으며, 이 염형태의 약물을 중합체 용액에 완전히 용해시켰다. 이 제형으로 부터의 약물의 분비속도를 상기 실시예 8에서와 동일하게 측정한 결과, 분비속도가 다소 낮은 것을 제외하고는 유리염기형태와 유사하였는 바, 1일이 지난 후에는 약물이 약 32%가 분비되었고 2일 후에는 40%, 5일 후에는 57%, 6일 후에는 64%, 7일 후에는 75%, 9일 후에는 82%, 12일 후에는 92%, 14일 후에는 약 100%가 분비되었다.
[실시예 10]
0.26DL/g의 고유점도와 약 10,000달톤의 이론 분자량을 가진 DL-PLA는 라우릴 알코올을 개시제로 하고 SnCl을 촉매로 하여 DL-락티드의 재환 중합반응에 의해 제조되었다. NMP에 중합체를 녹여 중량비로 50% 중합체 용액이 되게 하였다. 다량 (100㎕)의 중합체 용액을 토끼의 피부하에 주사하고 USP 음성 소성제의 조직반응과 비교하였다. 드레이즈 법에 따라 주사 후 즉히, 주사 후 1시간과 6시간, 7일, 14일, 21일에 희생되어질 때까지 매일 한 번씩 국소자극에 대한 시험부위의 징후를 측정하였다. 시험부위에서 1반응은 USP 음성 소성체 대조율과 동등하게 나타났다. 또한 중합체 용액(100㎕)을 비이글 개의 치분비물로 생성된 부위 차육하로 투여하였고 대조 부위는 염류 용액으로 씻어내었다. 상기 개는 매일 사망률, 약물독성 효과, 체중, 부분적 치은 자극을 시험하였다. 상기 동물들은 15일과 21일에 희생되었으며 대조부위와 시험부위간에 뚜렷한 차이는 없었다.
[실시예 11]
0.126DL/g 고유점도와 약 10,000정도의 분자량을 가진 DL-PLA를 NMP에 용해하여 중량비로 50% 중합체 용액이 되게 하였다. 중합체 용액에 SaCl를 가하여 중량비로 2.4% 분산이 되게 하여 게이지 23의 무딘 주사바늘이 장착된 1cc용약 주사기로 이물질을 그레이하운드 개의 치은낭에 주사하였다. 상기 물질은 주사의 좁은 팁에서 쉽게 흘러나왔고, 상기 중합체는 낭내에 타액과 유동체에 접촉될 때 필름이나 고체로 응집되거나 침전되었다. 상기 개는 낭주변 조직에 붙어 있는 낭내에 상기 물질의 덩어리가 남아 있는 약 2주 관찰되었는데 밝은 오렌지에서 엷은 흰색으로 천천히 변해갔다. 낭내에서 구액의 작은 양을 뽑기 위해 치은낭 입구에 작은 종이 조각으로 페리오스트립(Periostrip)을 써서 이식체를 포함하는 낭에서 구액을 2주 동안 채집하였다.
수집된 유동체의 부피는 종이조각의 저항역수로 변화를 측정하는 페리오트론을 써서 정량한다. 페리오트론을 사용하기 전에 기지부피의 세럼으로 표준화한다. 수집된 유동액을 포함하는 종이조각은 0.5% 부피비의 메탄올-염산 용액으로 추출하고 기지농도의 동일한 화합물을 기준으로 하여 약물의 양을 정량하는 액체 크로마토그래피에 주사한다. 종이조각에서 추출된 SaCl의 양은 약물 농도를 계산하기 위해 수집된 구액량으로 나눈다. 이러한 기술로, 중합체의 전달계를 가진 치은낭에서 구액내에 SaCl의 농도는 2주 동안의 관찰에서 거의 상수로 나타났다. 구액내에 SaCl 농도는 3일 후에 63.2㎍/㎖, 7일 후에 80.2㎍/㎖ 10일 후에 67.8㎍/㎖, 14일 후에 70.5㎍/㎖였다.
[실시예 12]
아크릴레이트 말단 예비중합체의 합성에 대한 예증의 제시되었다. 두 개의 말단 수산화기를 갖는 예비중합체 100g과 재증류된 THF 200㎖를 질소 기류하에서 첨가용 깔대기 기체 주입구 교반기, 고무관이 설치된 세 개의 목이 있는 500㎖ 둥근 바닥 플라스크에 넣는다. 플라스크를 냉수용상에 넣어 냉각하고 건조한 트리에틸아민(0.95당량/당량 OH)을 주사기로 넣었다. 첨가 깔대기에는 15㎖ THF에 녹은 15.4g 아크릴로일 클로라이드(0.95당량/당량 OH)를 충진하고 반응 혼합물을 교반하면서 1시간 동안 천천히 가한다. 혼합용액을 하룻동안 교반하고 실온이 되도록 방치하였다. 침전된 트리에틸아민 염산염을 여과에 의해 제거하고 여과액은 진공하에 증발시키면 엷은 노란색의 기름이 뜨는데 이것이 아크릴레이트-말단-예비중합체이다. 용매로서 CH2Cl2를 적용한 아실화도 같은 방법으로 진행하였다. 그러나 0℃에서 반응시간은 1시간 감소하여 반응혼합물은 실온에 도달하기 위해 1시간 동안 방치되었다. 2t3NHCl을 여과하고 여과액에 CH2Cl2(약 800㎖) 추가분을 가하여 여과액을 250㎖물로 여러차례 추출해냈다. 유기층은 NgSO4/Na2SO4로 건조시켜 여과하고 진공하에서 유상이 될 때까지 농축한다. 아크릴릭 예비중합체의 병을 호일로 싸서 미리 반응되는 것을 막기 위해 냉장고에 보관하였다.
측정하지 못함.
TMPTETA=트리메틸올프로판 트리에톡시트리아크릴레이트
AIBN=아조비스이소부티로니트릴
대기압하에서 공기중에서 경화됨.
디올 예비중합체를 이용함.

Claims (7)

  1. 물에 섞이는 생적합성 유기 용매 내에 용해된 생분해성 열가소성 중합체를 사용하여 고형의 이식조직을 원위치에서 형성시키기 위한 액체 조성물을 제조하는 방법.
  2. 제1항에 있어서, 상기 용매는 상기 중합체를 용해시킬 수 있는 제1용매와 상기 중합체를 용해시킬 수 없는 제2용매를 함유하는 이성분의 혼합용매로 이루어진 것으로서, 이 혼합용매에 존재하는 제1용매 및 제2용매는 상기 중합체가 용해되어질 수 있는 비율로 혼합되어 있으며, 상기 중합체는 원위치에서 액체 조성물로부터 침전되며, 그 결과 제1용매에 대한 제2용매의 비율이 높아지게 되는 방법.
  3. 제1항에 있어서, 추가로 생물학적 활성 성분을 사용하는 것인 방법.
  4. 제1항에 따른 방법으로 형성된 생분해성 이식조직.
  5. 제3항에 따른 방법으로 형성된 생분해성 이식조직.
  6. 체내에 투입되었을 때 소산되어 이식조직을 형성할 수 있는 생적합성 용매에 용해시킨 유효량이 비반응성 생적합성 중합체로 이루어진 것인 생분해성 이식조직을 원위치에서 형성시키기 위한 조성물.
  7. 제6항에 있어서, 유효량의 생물학적 활성 성분을 추가로 포함하는 조성물.
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Families Citing this family (838)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5693343A (en) 1984-03-16 1997-12-02 The United States Of America As Represented By The Secretary Of The Army Microparticle carriers of maximal uptake capacity by both M cells and non-M cells
US6410056B1 (en) 1984-03-16 2002-06-25 The United States Of America As Represented By The Secretary Of The Army Chemotherapeutic treatment of bacterial infections with an antibiotic encapsulated within a biodegradable polymeric matrix
USRE40786E1 (en) 1984-03-16 2009-06-23 The United States Of America As Represented By The Secretary Of The Army Vaccines against intracellular pathogens using antigens encapsulated within biodegradable-biocompatible microspheres
US6309669B1 (en) 1984-03-16 2001-10-30 The United States Of America As Represented By The Secretary Of The Army Therapeutic treatment and prevention of infections with a bioactive materials encapsulated within a biodegradable-biocompatible polymeric matrix
US20030161889A1 (en) * 1984-03-16 2003-08-28 Reid Robert H. Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres
US6217911B1 (en) 1995-05-22 2001-04-17 The United States Of America As Represented By The Secretary Of The Army sustained release non-steroidal, anti-inflammatory and lidocaine PLGA microspheres
US5904717A (en) * 1986-01-28 1999-05-18 Thm Biomedical, Inc. Method and device for reconstruction of articular cartilage
US5843156A (en) 1988-08-24 1998-12-01 Endoluminal Therapeutics, Inc. Local polymeric gel cellular therapy
US5575815A (en) * 1988-08-24 1996-11-19 Endoluminal Therapeutics, Inc. Local polymeric gel therapy
JP2836878B2 (ja) 1988-08-24 1998-12-14 スリピアン，マービン，ジェイ 生分解性高分子材料による管腔内封止
US5634946A (en) * 1988-08-24 1997-06-03 Focal, Inc. Polymeric endoluminal paving process
US5632727A (en) * 1988-10-03 1997-05-27 Atrix Laboratories, Inc. Biodegradable film dressing and method for its formation
US5725491A (en) * 1988-10-03 1998-03-10 Atrix Laboratories, Inc. Method of forming a biodegradable film dressing on tissue
US4938763B1 (en) * 1988-10-03 1995-07-04 Atrix Lab Inc Biodegradable in-situ forming implants and method of producing the same
US5702716A (en) * 1988-10-03 1997-12-30 Atrix Laboratories, Inc. Polymeric compositions useful as controlled release implants
US5487897A (en) 1989-07-24 1996-01-30 Atrix Laboratories, Inc. Biodegradable implant precursor
US5077049A (en) * 1989-07-24 1991-12-31 Vipont Pharmaceutical, Inc. Biodegradable system for regenerating the periodontium
US5324519A (en) * 1989-07-24 1994-06-28 Atrix Laboratories, Inc. Biodegradable polymer composition
US5525348A (en) * 1989-11-02 1996-06-11 Sts Biopolymers, Inc. Coating compositions comprising pharmaceutical agents
USRE37950E1 (en) 1990-04-24 2002-12-31 Atrix Laboratories Biogradable in-situ forming implants and methods of producing the same
NL9001428A (nl) * 1990-06-21 1992-01-16 Stichting Tech Wetenschapp Microporeuze buisvormige prothesen.
US5269785A (en) 1990-06-28 1993-12-14 Bonutti Peter M Apparatus and method for tissue removal
EP0489743A1 (en) * 1990-07-03 1992-06-17 Vipont Pharmaceutical, Inc. Intragingival delivery systems for treatment of periodontal disease
WO1992000747A1 (en) * 1990-07-12 1992-01-23 Sterilization Technical Services, Inc. Anti-thrombogenic and/or anti-microbial composition
US5410016A (en) * 1990-10-15 1995-04-25 Board Of Regents, The University Of Texas System Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
US5626863A (en) * 1992-02-28 1997-05-06 Board Of Regents, The University Of Texas System Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
US5462990A (en) * 1990-10-15 1995-10-31 Board Of Regents, The University Of Texas System Multifunctional organic polymers
US5620700A (en) * 1990-10-30 1997-04-15 Alza Corporation Injectable drug delivery system and method
WO1992019263A1 (en) 1991-04-24 1992-11-12 The United States Of America, As Represented By The Secretary Of The Army Oral-intestinal vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres
US6503277B2 (en) * 1991-08-12 2003-01-07 Peter M. Bonutti Method of transplanting human body tissue
AU2605592A (en) * 1991-10-15 1993-04-22 Atrix Laboratories, Inc. Polymeric compositions useful as controlled release implants
US5270047A (en) * 1991-11-21 1993-12-14 Kauffman Raymond F Local delivery of dipyridamole for the treatment of proliferative diseases
WO1993015787A1 (en) * 1992-02-12 1993-08-19 Chandler Jerry W Biodegradable stent
US5573934A (en) 1992-04-20 1996-11-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
BR9306038A (pt) 1992-02-28 1998-01-13 Univ Texas Hidrogéis biodegradáveis fotopolimerizáveis como materiais de contato de tecidos e condutores de liberação controlada
EP0560014A1 (en) * 1992-03-12 1993-09-15 Atrix Laboratories, Inc. Biodegradable film dressing and method for its formation
US5384333A (en) * 1992-03-17 1995-01-24 University Of Miami Biodegradable injectable drug delivery polymer
US5540240A (en) * 1992-03-26 1996-07-30 Bauer; William Intranasal septal fastener driving method
US5370294A (en) * 1992-03-26 1994-12-06 Bauer; William Intranasal septal stapling device and method
FR2689400B1 (fr) * 1992-04-03 1995-06-23 Inoteb Materiau pour prothese osseuse contenant des particules de carbonate de calcium dispersees dans une matrice polymere bioresorbable.
GB9211268D0 (en) * 1992-05-28 1992-07-15 Ici Plc Salts of basic peptides with carboxyterminated polyesters
NZ247712A (en) * 1992-06-19 1995-04-27 Colgate Palmolive Co Oral composition comprising an anti-bacterial compound, a water-insoluble biodegradable polymer, and an organic solvent
US5242910A (en) † 1992-10-13 1993-09-07 The Procter & Gamble Company Sustained release compositions for treating periodontal disease
US5910520A (en) * 1993-01-15 1999-06-08 Mcneil-Ppc, Inc. Melt processable biodegradable compositions and articles made therefrom
US5981568A (en) 1993-01-28 1999-11-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5800373A (en) * 1995-03-23 1998-09-01 Focal, Inc. Initiator priming for improved adherence of gels to substrates
US5749968A (en) * 1993-03-01 1998-05-12 Focal, Inc. Device for priming for improved adherence of gels to substrates
EP0690736B1 (en) * 1993-03-23 1998-11-11 Focal, Inc. Apparatus and method for local application of polymeric material to tissue
US6004547A (en) 1997-09-29 1999-12-21 Focal, Inc. Apparatus and method for local application of polymeric material to tissue
US5321113A (en) * 1993-05-14 1994-06-14 Ethicon, Inc. Copolymers of an aromatic anhydride and aliphatic ester
US6939546B2 (en) 1993-05-21 2005-09-06 The United States Of America As Represented By The Secretary Of The Army Model for testing immunogenicity of peptides
US5925065A (en) * 1993-06-11 1999-07-20 United States Surgical Corporation Coated gut suture
CA2123647C (en) * 1993-06-11 2007-04-17 Steven L. Bennett Bioabsorbable copolymer and coating composition containing same
US5425949A (en) * 1993-06-11 1995-06-20 United States Surgical Corporation Bioabsorbable copolymer and coating composition containing same
NZ511762A (en) 1993-07-19 2003-09-26 Univ British Columbia Anti-angiogenic compositions and methods of use
JP3220331B2 (ja) * 1993-07-20 2001-10-22 エチコン・インコーポレーテツド 非経口投与用の吸収性液体コポリマー類
US6908910B2 (en) * 1993-08-06 2005-06-21 The Children's Medical Center Corporation Estrogenic compounds as anti-mitotic agents
CA2128912A1 (en) * 1993-08-17 1995-02-18 Zygmunt Teodorczyk Modified phenol-aldehyde resin and binder system
US5468855A (en) * 1993-09-09 1995-11-21 Ciba-Geigy Corporation Bislactones
US5681873A (en) * 1993-10-14 1997-10-28 Atrix Laboratories, Inc. Biodegradable polymeric composition
CA2175049A1 (en) * 1993-10-28 1995-05-04 Timothy Ringeisen Improved process and device for treating and healing a bone void
FR2715309B1 (fr) * 1994-01-24 1996-08-02 Imedex Composition adhésive, à usage chirurgical, à base de collagène modifié par coupure oxydative et non réticulé.
CA2140053C (en) * 1994-02-09 2000-04-04 Joel S. Rosenblatt Collagen-based injectable drug delivery system and its use
US6074840A (en) 1994-02-18 2000-06-13 The Regents Of The University Of Michigan Recombinant production of latent TGF-beta binding protein-3 (LTBP-3)
US5763416A (en) * 1994-02-18 1998-06-09 The Regent Of The University Of Michigan Gene transfer into bone cells and tissues
US5942496A (en) * 1994-02-18 1999-08-24 The Regent Of The University Of Michigan Methods and compositions for multiple gene transfer into bone cells
US5962427A (en) * 1994-02-18 1999-10-05 The Regent Of The University Of Michigan In vivo gene transfer methods for wound healing
US5502092A (en) * 1994-02-18 1996-03-26 Minnesota Mining And Manufacturing Company Biocompatible porous matrix of bioabsorbable material
US20020193338A1 (en) * 1994-02-18 2002-12-19 Goldstein Steven A. In vivo gene transfer methods for wound healing
US6551618B2 (en) * 1994-03-15 2003-04-22 University Of Birmingham Compositions and methods for delivery of agents for neuronal regeneration and survival
ATE209907T1 (de) * 1994-04-08 2001-12-15 Atrix Lab Inc Flüssige mittel zur wirkstoffabgabe
WO1995028124A2 (en) * 1994-04-08 1995-10-26 Atrix Laboratories, Inc. An adjunctive polymer system for use with medical device
US6140452A (en) * 1994-05-06 2000-10-31 Advanced Bio Surfaces, Inc. Biomaterial for in situ tissue repair
US20050043808A1 (en) * 1994-05-06 2005-02-24 Advanced Bio Surfaces, Inc. Knee joint prosthesis
US5556429A (en) * 1994-05-06 1996-09-17 Advanced Bio Surfaces, Inc. Joint resurfacing system
US5981825A (en) 1994-05-13 1999-11-09 Thm Biomedical, Inc. Device and methods for in vivo culturing of diverse tissue cells
US6447796B1 (en) 1994-05-16 2002-09-10 The United States Of America As Represented By The Secretary Of The Army Sustained release hydrophobic bioactive PLGA microspheres
US6855331B2 (en) 1994-05-16 2005-02-15 The United States Of America As Represented By The Secretary Of The Army Sustained release hydrophobic bioactive PLGA microspheres
DK63894A (da) * 1994-06-06 1996-01-08 Meadox Medicals Inc Kateter med stent samt fremgangsmåde til fremstilling af et sådant kateter med stent
US5665063A (en) * 1994-06-24 1997-09-09 Focal, Inc. Methods for application of intraluminal photopolymerized gels
US5531735A (en) * 1994-09-27 1996-07-02 Hercules Incorporated Medical devices containing triggerable disintegration agents
AU1287895A (en) * 1994-10-03 1996-04-26 Otogen Corporation Differentially biodegradable biomedical implants
AU706434B2 (en) 1994-10-18 1999-06-17 Ethicon Inc. Injectable liquid copolymers for soft tissue repair and augmentation
US5599852A (en) * 1994-10-18 1997-02-04 Ethicon, Inc. Injectable microdispersions for soft tissue repair and augmentation
US6335383B1 (en) 1994-10-18 2002-01-01 Ethicon, Inc. Microdispersions for coating surgical devices
US5607686A (en) * 1994-11-22 1997-03-04 United States Surgical Corporation Polymeric composition
US5550172A (en) * 1995-02-07 1996-08-27 Ethicon, Inc. Utilization of biocompatible adhesive/sealant materials for securing surgical devices
US5900245A (en) 1996-03-22 1999-05-04 Focal, Inc. Compliant tissue sealants
DE69637198T2 (de) * 1995-03-23 2008-05-08 Genzyme Corp., Cambridge Redox und photoinitiatorsystem zur grundierung von verbesserter adhäsion von gelen zu substraten
AU704222B2 (en) * 1995-03-24 1999-04-15 Genzyme Corporation Reduction of adhesions using controlled delivery of active oxygen inhibitors
US5612052A (en) * 1995-04-13 1997-03-18 Poly-Med, Inc. Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof
US6413539B1 (en) 1996-10-31 2002-07-02 Poly-Med, Inc. Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof
US6551610B2 (en) 1995-04-13 2003-04-22 Poly-Med, Inc. Multifaceted compositions for post-surgical adhesion prevention
AU5069796A (en) * 1995-04-28 1996-11-07 Ethicon Inc. Solventless tipping of braided surgical ligature
US7033608B1 (en) 1995-05-22 2006-04-25 The United States Of America As Represented By The Secretary Of The Army “Burst-free” sustained release poly-(lactide/glycolide) microspheres
US6902743B1 (en) 1995-05-22 2005-06-07 The United States Of America As Represented By The Secretary Of The Army Therapeutic treatment and prevention of infections with a bioactive material(s) encapuslated within a biodegradable-bio-compatable polymeric matrix
US7833543B2 (en) * 1995-06-07 2010-11-16 Durect Corporation High viscosity liquid controlled delivery system and medical or surgical device
US5722950A (en) * 1995-06-07 1998-03-03 Atrix Laboratories, Inc. Method for remote delivery of an aerosolized liquid
US5968542A (en) * 1995-06-07 1999-10-19 Southern Biosystems, Inc. High viscosity liquid controlled delivery system as a device
US5747058A (en) * 1995-06-07 1998-05-05 Southern Biosystems, Inc. High viscosity liquid controlled delivery system
US6413536B1 (en) 1995-06-07 2002-07-02 Southern Biosystems, Inc. High viscosity liquid controlled delivery system and medical or surgical device
WO1996039995A1 (en) * 1995-06-07 1996-12-19 Southern Biosystems, Inc. High viscosity liquid controlled delivery system
US5779673A (en) * 1995-06-26 1998-07-14 Focal, Inc. Devices and methods for application of intraluminal photopolymerized gels
US5580568A (en) * 1995-07-27 1996-12-03 Micro Therapeutics, Inc. Cellulose diacetate compositions for use in embolizing blood vessels
US5667767A (en) * 1995-07-27 1997-09-16 Micro Therapeutics, Inc. Compositions for use in embolizing blood vessels
ATE342295T1 (de) * 1995-07-28 2006-11-15 Genzyme Corp Biologische abbaubare multiblokhydrogene und ihre verwendung wie trägerstoffe fur kontrollierte freisetzung pharmakologisch activen werstoffe und gewebekontaktmaterialen
US5702717A (en) * 1995-10-25 1997-12-30 Macromed, Inc. Thermosensitive biodegradable polymers based on poly(ether-ester)block copolymers
US5665428A (en) * 1995-10-25 1997-09-09 Macromed, Inc. Preparation of peptide containing biodegradable microspheres by melt process
US5736152A (en) * 1995-10-27 1998-04-07 Atrix Laboratories, Inc. Non-polymeric sustained release delivery system
FR2741628B1 (fr) * 1995-11-29 1998-02-06 Centre Nat Rech Scient Nouveaux hydrogels a base de copolymeres trisequences et leur application notamment a la liberation progressive de principes actifs
US7888466B2 (en) 1996-01-11 2011-02-15 Human Genome Sciences, Inc. Human G-protein chemokine receptor HSATU68
US5980945A (en) * 1996-01-16 1999-11-09 Societe De Conseils De Recherches Et D'applications Scientifique S.A. Sustained release drug formulations
US5997568A (en) * 1996-01-19 1999-12-07 United States Surgical Corporation Absorbable polymer blends and surgical articles fabricated therefrom
US5985312A (en) * 1996-01-26 1999-11-16 Brown University Research Foundation Methods and compositions for enhancing the bioadhesive properties of polymers
US6368586B1 (en) 1996-01-26 2002-04-09 Brown University Research Foundation Methods and compositions for enhancing the bioadhesive properties of polymers
US5702361A (en) * 1996-01-31 1997-12-30 Micro Therapeutics, Inc. Method for embolizing blood vessels
CA2246615C (en) * 1996-02-20 2006-05-09 Massachusetts Institute Of Technology Biodegradable polymer networks for use in orthopedic and dental applications
US5747060A (en) * 1996-03-26 1998-05-05 Euro-Celtique, S.A. Prolonged local anesthesia with colchicine
US5921954A (en) * 1996-07-10 1999-07-13 Mohr, Jr.; Lawrence G. Treating aneurysms by applying hardening/softening agents to hardenable/softenable substances
US7022105B1 (en) * 1996-05-06 2006-04-04 Novasys Medical Inc. Treatment of tissue in sphincters, sinuses and orifices
IL118235A0 (en) * 1996-05-13 1996-09-12 Univ Ben Gurion Composition and method for forming biodegradable implants in situ and uses of these implants
NZ505584A (en) 1996-05-24 2002-04-26 Univ British Columbia Delivery of a therapeutic agent to the smooth muscle cells of a body passageway via an adventia
US6103254A (en) * 1996-05-31 2000-08-15 Micro Therapeutics, Inc. Methods for sterilizing male mammals
AU2745497A (en) * 1996-05-31 1998-01-05 Micro Therapeutics, Inc. Compositions for use in embolizing blood vessels
US5955096A (en) * 1996-06-25 1999-09-21 Brown University Research Foundation Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients
US20030077317A1 (en) * 1996-06-25 2003-04-24 Brown University Research Foundation Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients
US6368356B1 (en) 1996-07-11 2002-04-09 Scimed Life Systems, Inc. Medical devices comprising hydrogel polymers having improved mechanical properties
US6060534A (en) 1996-07-11 2000-05-09 Scimed Life Systems, Inc. Medical devices comprising ionically and non-ionically crosslinked polymer hydrogels having improved mechanical properties
US8353908B2 (en) 1996-09-20 2013-01-15 Novasys Medical, Inc. Treatment of tissue in sphincters, sinuses, and orifices
US8003705B2 (en) * 1996-09-23 2011-08-23 Incept Llc Biocompatible hydrogels made with small molecule precursors
US20090324721A1 (en) * 1996-09-23 2009-12-31 Jack Kennedy Hydrogels Suitable For Use In Polyp Removal
WO1998012274A1 (en) * 1996-09-23 1998-03-26 Chandrashekar Pathak Methods and devices for preparing protein concentrates
ZA978537B (en) 1996-09-23 1998-05-12 Focal Inc Polymerizable biodegradable polymers including carbonate or dioxanone linkages.
US5800412A (en) * 1996-10-10 1998-09-01 Sts Biopolymers, Inc. Hydrophilic coatings with hydrating agents
US6106473A (en) 1996-11-06 2000-08-22 Sts Biopolymers, Inc. Echogenic coatings
US7229413B2 (en) 1996-11-06 2007-06-12 Angiotech Biocoatings Corp. Echogenic coatings with overcoat
EP0873145A2 (en) 1996-11-15 1998-10-28 Advanced Bio Surfaces, Inc. Biomaterial system for in situ tissue repair
ATE318580T1 (de) * 1996-12-20 2006-03-15 Alza Corp Gelzusammensetzungen und verfahren
AU5522798A (en) 1996-12-31 1998-07-31 Kimberly-Clark Worldwide, Inc. Water-responsive polymer compositions and method of making the same
DE19701912C1 (de) * 1997-01-10 1998-05-14 Jenapharm Gmbh Injizierbares Implantat
US6338726B1 (en) 1997-02-06 2002-01-15 Vidacare, Inc. Treating urinary and other body strictures
US6630168B1 (en) 1997-02-20 2003-10-07 Biomedicines, Inc. Gel delivery vehicles for anticellular proliferative agents
DE69832288T2 (de) * 1997-03-20 2006-07-13 Genzyme Corp., Cambridge Biologisch abbaubarer gewebespreizer
ATE278397T1 (de) 1997-03-31 2004-10-15 Boston Scient Ltd Verwendung von cytoskelettinhibitoren zur vorbeugung der restenose
KR20010020432A (ko) 1997-04-30 2001-03-15 토마스 씨. 서 폴리(고리지방족 포스포에스테르) 화합물로 이루어진 생분해성 조성물, 약품 및 그의 이용방법
US20060025328A1 (en) * 1997-05-28 2006-02-02 Burns Patrick J Compositions suitable for controlled release of the hormone GnRH and its analogs
DE59813940D1 (de) 1997-06-05 2007-04-19 Roland Bodmeier Multiphasensystem
DE19724784A1 (de) * 1997-06-05 1998-12-10 Roland Prof Dr Bodmeier Verfahren zur in-situ Herstellung von Partikeln
WO1998055147A2 (en) 1997-06-06 1998-12-10 Battelle Memorial Institute Reversible geling co-polymer and method of making
US5962006A (en) * 1997-06-17 1999-10-05 Atrix Laboratories, Inc. Polymer formulation for prevention of surgical adhesions
DE19726412A1 (de) * 1997-06-21 1998-12-24 Merck Patent Gmbh Implantatmaterial mit einer Träger-Wirkstoff-Kombination
US7923250B2 (en) 1997-07-30 2011-04-12 Warsaw Orthopedic, Inc. Methods of expressing LIM mineralization protein in non-osseous cells
US6300127B1 (en) 1997-07-30 2001-10-09 Emory University Bone mineralization proteins, DNA, vectors, expression systems
US6075118A (en) * 1997-07-31 2000-06-13 Kimberly-Clark Worldwide, Inc. Water-responsive, biodegradable film compositions comprising polylactide and polyvinyl alcohol, and a method for making the films
US6552162B1 (en) 1997-07-31 2003-04-22 Kimberly-Clark Worldwide, Inc. Water-responsive, biodegradable compositions and films and articles comprising a blend of polylactide and polyvinyl alcohol and methods for making the same
US5945480A (en) * 1997-07-31 1999-08-31 Kimberly-Clark Worldwide, Inc. Water-responsive, biodegradable fibers comprising polylactide modified polylactide and polyvinyl alcohol, and method for making the fibers
US5952433A (en) * 1997-07-31 1999-09-14 Kimberly-Clark Worldwide, Inc. Modified polyactide compositions and a reactive-extrusion process to make the same
ZA987019B (en) * 1997-08-06 1999-06-04 Focal Inc Hemostatic tissue sealants
US9023031B2 (en) * 1997-08-13 2015-05-05 Verathon Inc. Noninvasive devices, methods, and systems for modifying tissues
AUPO907697A0 (en) 1997-09-09 1997-10-02 Day, Robert Edward Chemical supplementation of bone
US5989463A (en) * 1997-09-24 1999-11-23 Alkermes Controlled Therapeutics, Inc. Methods for fabricating polymer-based controlled release devices
US6117949A (en) * 1998-10-01 2000-09-12 Macromed, Inc. Biodegradable low molecular weight triblock poly (lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties
US6004573A (en) * 1997-10-03 1999-12-21 Macromed, Inc. Biodegradable low molecular weight triblock poly(lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties
US6201072B1 (en) 1997-10-03 2001-03-13 Macromed, Inc. Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties
US8668737B2 (en) 1997-10-10 2014-03-11 Senorx, Inc. Tissue marking implant
US7637948B2 (en) * 1997-10-10 2009-12-29 Senorx, Inc. Tissue marking implant
US6569417B2 (en) 1997-10-10 2003-05-27 Micro Therapeutics, Inc. Methods for treating urinary incontinence in mammals
US6417247B1 (en) * 1997-10-14 2002-07-09 Beth L. Armstrong Polymer/ceramic composites
JP2001520979A (ja) * 1997-10-27 2001-11-06 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 網膜傷の閉鎖のための方法及び医薬組成物
US20020164374A1 (en) * 1997-10-29 2002-11-07 John Jackson Polymeric systems for drug delivery and uses thereof
US6193991B1 (en) 1997-10-29 2001-02-27 Atul J. Shukla Biodegradable delivery systems of biologically active substances
US6015541A (en) * 1997-11-03 2000-01-18 Micro Therapeutics, Inc. Radioactive embolizing compositions
JP2001523515A (ja) * 1997-11-21 2001-11-27 インテラグ 哺乳動物の膣に挿入する装置と製造および使用方法
NZ330596A (en) 1998-06-05 2001-02-23 Dec Res Intravaginal devices allowing for increased uptake of active ingredients
HUP0101250A3 (en) * 1998-01-29 2006-06-28 Poly Med Inc Anderson Absorbable microparticles
ES2194437T3 (es) 1998-01-29 2003-11-16 Kinerton Ltd Procedimiento para producir microparticulas absorbibles.
US20100114087A1 (en) * 1998-02-19 2010-05-06 Edwards Stuart D Methods and devices for treating urinary incontinence
ES2359973T3 (es) * 1998-03-19 2011-05-30 MERCK SHARP & DOHME CORP. Composiciones poliméricas líquidas para la liberación controlada de sustancias bioactivas.
US6161034A (en) * 1999-02-02 2000-12-12 Senorx, Inc. Methods and chemical preparations for time-limited marking of biopsy sites
US7087244B2 (en) * 2000-09-28 2006-08-08 Battelle Memorial Institute Thermogelling oligopeptide polymers
US6841617B2 (en) * 2000-09-28 2005-01-11 Battelle Memorial Institute Thermogelling biodegradable aqueous polymer solution
US20040228794A1 (en) * 1998-04-10 2004-11-18 Battelle Memorial Institute Therapeutic agent carrier compositions
US7128927B1 (en) 1998-04-14 2006-10-31 Qlt Usa, Inc. Emulsions for in-situ delivery systems
AU766959B2 (en) * 1998-04-20 2003-10-30 Genzyme Corporation Drug delivery of proteins from polymeric blends
US6177094B1 (en) 1998-04-30 2001-01-23 United States Surgical Corporation Bioabsorbable blends and coating composition containing same
US6350518B1 (en) 1998-06-01 2002-02-26 Kimberly-Clark Worldwide, Inc. Methods of making blend compositions of an unmodified poly vinyl alcohol and a thermoplastic elastomer
US6933326B1 (en) 1998-06-19 2005-08-23 Lifecell Coporation Particulate acellular tissue matrix
MXPA00000009A (es) 1998-06-22 2005-09-08 Autologous Wound Therapy Inc Solicitud para patente de utilidad para curativo de heridas mejorado enriquecido con plaquetas.
US6245345B1 (en) 1998-07-07 2001-06-12 Atrix Laboratories, Inc. Filamentous porous films and methods for producing the same
US6261583B1 (en) 1998-07-28 2001-07-17 Atrix Laboratories, Inc. Moldable solid delivery system
JP4159254B2 (ja) * 1998-08-14 2008-10-01 インセプト エルエルシー ヒドロゲルのインサイチュ形成のための方法および装置
US6605294B2 (en) * 1998-08-14 2003-08-12 Incept Llc Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels
US6632457B1 (en) 1998-08-14 2003-10-14 Incept Llc Composite hydrogel drug delivery systems
US6179862B1 (en) 1998-08-14 2001-01-30 Incept Llc Methods and apparatus for in situ formation of hydrogels
US6152943A (en) * 1998-08-14 2000-11-28 Incept Llc Methods and apparatus for intraluminal deposition of hydrogels
US6818018B1 (en) * 1998-08-14 2004-11-16 Incept Llc In situ polymerizable hydrogels
US6703047B2 (en) 2001-02-02 2004-03-09 Incept Llc Dehydrated hydrogel precursor-based, tissue adherent compositions and methods of use
US6325991B1 (en) * 1998-08-24 2001-12-04 Susan E. Draheim Methods and compositions for treating periodontal disease with an inhibitor of secretory phospholipase A2
US6153212A (en) * 1998-10-02 2000-11-28 Guilford Pharmaceuticals Inc. Biodegradable terephthalate polyester-poly (phosphonate) compositions, articles, and methods of using the same
US6419709B1 (en) * 1998-10-02 2002-07-16 Guilford Pharmaceuticals, Inc. Biodegradable terephthalate polyester-poly(Phosphite) compositions, articles, and methods of using the same
US6565874B1 (en) * 1998-10-28 2003-05-20 Atrix Laboratories Polymeric delivery formulations of leuprolide with improved efficacy
US6143314A (en) * 1998-10-28 2000-11-07 Atrix Laboratories, Inc. Controlled release liquid delivery compositions with low initial drug burst
US7767708B2 (en) * 1998-11-04 2010-08-03 Schering-Plough Animal Health Corp. Growth stimulant compositions
US6110484A (en) 1998-11-24 2000-08-29 Cohesion Technologies, Inc. Collagen-polymer matrices with differential biodegradability
WO2000033764A1 (en) * 1998-12-04 2000-06-15 Pathak Chandrashekhar P Biocompatible crosslinked polymers
US20080114092A1 (en) * 1998-12-04 2008-05-15 Incept Llc Adhesion barriers applicable by minimally invasive surgery and methods of use thereof
US6200550B1 (en) 1998-12-11 2001-03-13 Q-Pharma, Inc. Oral care compositions comprising coenzyme Q10
US6231613B1 (en) 1998-12-15 2001-05-15 Enteric Medical Technologies, Inc. Methods for soft tissue augmentation in mammals
US7983734B2 (en) 2003-05-23 2011-07-19 Senorx, Inc. Fibrous marker and intracorporeal delivery thereof
US7651505B2 (en) 2002-06-17 2010-01-26 Senorx, Inc. Plugged tip delivery for marker placement
US20090216118A1 (en) * 2007-07-26 2009-08-27 Senorx, Inc. Polysaccharide markers
US6725083B1 (en) 1999-02-02 2004-04-20 Senorx, Inc. Tissue site markers for in VIVO imaging
US8361082B2 (en) 1999-02-02 2013-01-29 Senorx, Inc. Marker delivery device with releasable plug
US9820824B2 (en) 1999-02-02 2017-11-21 Senorx, Inc. Deployment of polysaccharide markers for treating a site within a patent
US8498693B2 (en) 1999-02-02 2013-07-30 Senorx, Inc. Intracorporeal marker and marker delivery device
US6862470B2 (en) 1999-02-02 2005-03-01 Senorx, Inc. Cavity-filling biopsy site markers
DE19908753C2 (de) 1999-02-20 2003-10-02 Jenapharm Gmbh Bioabbaubare, injizierbare Oligomer-Polymer-Zusammensetzung
US6303100B1 (en) 1999-03-19 2001-10-16 Micro Therapeutics, Inc. Methods for inhibiting the formation of potential endoleaks associated with endovascular repair of abdominal aortic aneurysms
US6203779B1 (en) 1999-03-19 2001-03-20 Charlie Ricci Methods for treating endoleaks during endovascular repair of abdominal aortic aneurysms
WO2000056376A1 (en) * 1999-03-25 2000-09-28 Metabolix, Inc. Medical devices and applications of polyhydroxyalkanoate polymers
US6206927B1 (en) 1999-04-02 2001-03-27 Barry M. Fell Surgically implantable knee prothesis
US7341602B2 (en) * 1999-05-10 2008-03-11 Fell Barry M Proportioned surgically implantable knee prosthesis
DE19916131A1 (de) * 1999-04-09 2000-10-26 S & C Polymer Silicon & Compos Adhesivsystem für Silicone
DE60038010T2 (de) 1999-04-12 2009-03-05 Cornell Research Foundation, Inc. Hydrogel-formendes system mit hydrophoben und hydrophilen komponenten
US6716445B2 (en) * 1999-04-12 2004-04-06 Cornell Research Foundation, Inc. Hydrogel entrapping therapeutic agent and stent with coating comprising this
EP1173517A4 (en) * 1999-04-26 2006-06-28 California Inst Of Techn HYDROGELS CONSTITUTING IN SITU
US6858229B1 (en) 1999-04-26 2005-02-22 California Institute Of Technology In situ forming hydrogels
US6554851B1 (en) 1999-05-07 2003-04-29 Scimed Life Systems, Inc. Methods of sealing an injection site
US6911044B2 (en) * 1999-05-10 2005-06-28 Barry M. Fell Surgically implantable knee prosthesis having medially shifted tibial surface
US6923831B2 (en) * 1999-05-10 2005-08-02 Barry M. Fell Surgically implantable knee prosthesis having attachment apertures
US6893463B2 (en) * 1999-05-10 2005-05-17 Barry M. Fell Surgically implantable knee prosthesis having two-piece keyed components
US6866684B2 (en) 1999-05-10 2005-03-15 Barry M. Fell Surgically implantable knee prosthesis having different tibial and femoral surface profiles
US6855165B2 (en) * 1999-05-10 2005-02-15 Barry M. Fell Surgically implantable knee prosthesis having enlarged femoral surface
US6966928B2 (en) 1999-05-10 2005-11-22 Fell Barry M Surgically implantable knee prosthesis having keels
US6241719B1 (en) 1999-05-13 2001-06-05 Micro Therapeutics, Inc. Method for forming a radioactive stent
US6333020B1 (en) 1999-05-13 2001-12-25 Micro Therapeutics, Inc. Methods for treating AVM's using radio active compositions
WO2000071170A1 (en) 1999-05-21 2000-11-30 Micro Therapeutics, Inc. Novel high viscosity embolizing compositions
US6645167B1 (en) * 1999-05-21 2003-11-11 Micro Therapeutics, Inc. Methods for embolizing vascular sites with an embolizing composition
US7018365B2 (en) 1999-05-21 2006-03-28 Micro Therapeutics, Inc. Threaded syringe with quick stop
AU5144600A (en) 1999-05-21 2000-12-12 Micro Therapeutics, Inc. Methods for embolizing vascular sites with an embolizing composition
EP1949890A3 (en) 1999-06-04 2011-05-18 ALZA Corporation Implantable gel compositions and method of manufacture
WO2000074650A2 (en) * 1999-06-04 2000-12-14 Alza Corporation Implantable gel compositions and method of manufacture
IL146801A0 (en) * 1999-06-11 2002-07-25 Pro Duct Health Inc Gel composition for filling a breast milk duct prior to surgical excision of the duct or other breast tissue
US6575991B1 (en) 1999-06-17 2003-06-10 Inrad, Inc. Apparatus for the percutaneous marking of a lesion
US6521431B1 (en) 1999-06-22 2003-02-18 Access Pharmaceuticals, Inc. Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments
US6541020B1 (en) * 1999-07-09 2003-04-01 Trimeris, Inc. Methods and compositions for administration of therapeutic reagents
US20020095157A1 (en) 1999-07-23 2002-07-18 Bowman Steven M. Graft fixation device combination
US6179840B1 (en) 1999-07-23 2001-01-30 Ethicon, Inc. Graft fixation device and method
US7008635B1 (en) * 1999-09-10 2006-03-07 Genzyme Corporation Hydrogels for orthopedic repair
US7025980B1 (en) 1999-09-14 2006-04-11 Tepha, Inc. Polyhydroxyalkanoate compositions for soft tissue repair, augmentation, and viscosupplementation
US8226598B2 (en) * 1999-09-24 2012-07-24 Tolmar Therapeutics, Inc. Coupling syringe system and methods for obtaining a mixed composition
US20020055708A1 (en) * 1999-09-24 2002-05-09 Peterson Kenneth R. Coupling syringe system and methods for obtaining a mixed composition
US6420378B1 (en) 1999-10-15 2002-07-16 Supergen, Inc. Inhibition of abnormal cell proliferation with camptothecin and combinations including the same
CA2685349C (en) * 1999-11-15 2013-09-17 Bio Syntech Canada Inc. Temperature-controlled and ph-dependant self-gelling biopolymeric aqueous solution
US6461631B1 (en) 1999-11-16 2002-10-08 Atrix Laboratories, Inc. Biodegradable polymer composition
US6682754B2 (en) * 1999-11-24 2004-01-27 Willmar Poultry Company, Inc. Ovo delivery of an immunogen containing implant
US20030158302A1 (en) * 1999-12-09 2003-08-21 Cyric Chaput Mineral-polymer hybrid composition
WO2001041821A1 (en) * 1999-12-09 2001-06-14 Biosyntech Canada Inc. Mineral-polymer hybrid composition
US20010037091A1 (en) * 1999-12-29 2001-11-01 Wironen John F. System for reconstituting pastes and methods of using same
DE10190041D2 (de) * 2000-01-11 2002-12-05 Roland Bodmeier Implantate, Partikel
US7097855B1 (en) 2000-01-31 2006-08-29 Massachusetts Institute Of Technology Transdermal thermal polymerization
AU2001236731A1 (en) 2000-02-10 2001-08-20 Harmonia Medical Technologies Inc. Transurethral volume reduction of the prostate (tuvor)
FI20000317A (fi) * 2000-02-15 2001-08-16 Jvs Polymers Oy Biologisesti hajoava materiaali
DE60130544T2 (de) 2000-03-13 2008-06-26 Biocure, Inc. Embolische zusammensetzungen
US6652883B2 (en) * 2000-03-13 2003-11-25 Biocure, Inc. Tissue bulking and coating compositions
US6626945B2 (en) * 2000-03-14 2003-09-30 Chondrosite, Llc Cartilage repair plug
US6632246B1 (en) 2000-03-14 2003-10-14 Chondrosite, Llc Cartilage repair plug
US7160931B2 (en) * 2000-03-15 2007-01-09 Yu-Ling Cheng Thermally reversible implant and filler
US7193007B2 (en) * 2000-03-15 2007-03-20 Yu-Ling Cheng Environment responsive gelling copolymer
US20030211974A1 (en) * 2000-03-21 2003-11-13 Brodbeck Kevin J. Gel composition and methods
US6566144B1 (en) 2000-03-27 2003-05-20 Atrix Laboratories Cover plate for use in lyophilization
US6626870B1 (en) 2000-03-27 2003-09-30 Artix Laboratories, Inc. Stoppering method to maintain sterility
EP1142596A1 (en) * 2000-04-03 2001-10-10 Universiteit Gent Compositions of crosslinkable prepolymers for use in therapeutically active biodegradable implants
AU5911101A (en) 2000-04-19 2001-10-30 Genentech Inc Sustained release formulations
US6800671B1 (en) 2000-04-21 2004-10-05 Britesmile, Inc. Low peak exotherm curable compositions
US6550482B1 (en) * 2000-04-21 2003-04-22 Vascular Control Systems, Inc. Methods for non-permanent occlusion of a uterine artery
US7018645B1 (en) 2000-04-27 2006-03-28 Macromed, Inc. Mixtures of various triblock polyester polyethylene glycol copolymers having improved gel properties
AU2001245346A1 (en) * 2000-06-28 2002-01-08 Atul J. Shukla Biodegradable vehicles and delivery systems of biologically active substances
NZ523763A (en) * 2000-06-29 2005-02-25 Biosyntech Canada Inc Compostion and method for the repair and regeneration of cartilage and other tissues
GB0017999D0 (en) * 2000-07-21 2000-09-13 Smithkline Beecham Biolog Novel device
DE10037983B4 (de) * 2000-08-03 2006-04-13 Stefan Zikeli Polymerzusammensetzung und daraus hergestellter Formkörper mit einem Gehalt an Alkaloid
AU2001285488A1 (en) * 2000-08-28 2002-03-13 Advanced Bio Surfaces, Inc Method for mammalian joint resurfacing
US6620196B1 (en) * 2000-08-30 2003-09-16 Sdgi Holdings, Inc. Intervertebral disc nucleus implants and methods
DE10044545A1 (de) * 2000-09-05 2002-04-04 Roland Bodmeier Retardpartikeldispersion
ATE377048T1 (de) * 2000-09-06 2007-11-15 Ap Pharma Inc Abbaubare polyacetal-polymere
US7306591B2 (en) 2000-10-02 2007-12-11 Novasys Medical, Inc. Apparatus and methods for treating female urinary incontinence
US20040115236A1 (en) * 2000-10-06 2004-06-17 Chan Tai Wah Devices and methods for management of inflammation
WO2002030487A2 (en) * 2000-10-11 2002-04-18 Micro Thereapeutics, Inc. Methods for treating aneurysms
US8470359B2 (en) 2000-11-13 2013-06-25 Qlt Usa, Inc. Sustained release polymer
US6565601B2 (en) * 2000-11-15 2003-05-20 Micro Therapeutics, Inc. Methods for vascular reconstruction of diseased arteries
US20040091540A1 (en) * 2000-11-15 2004-05-13 Desrosiers Eric Andre Method for restoring a damaged or degenerated intervertebral disc
US6726898B2 (en) 2000-11-17 2004-04-27 Gary R. Jernberg Local delivery of agents for disruption and inhibition of bacterial biofilm for treatment of periodontal disease
US6576226B1 (en) 2000-11-17 2003-06-10 Gary R. Jernberg Local delivery of agents for disruption and inhibition of bacterial biofilm for treatment of periodontal disease
CA2775170C (en) * 2000-11-20 2017-09-05 Senorx, Inc. An intracorporeal marker delivery system for marking a tissue site
US6648911B1 (en) 2000-11-20 2003-11-18 Avantec Vascular Corporation Method and device for the treatment of vulnerable tissue site
US20020106406A1 (en) * 2000-12-08 2002-08-08 Mchugh Anthony J. Crystallizable/non-crystallizable polymer composites
US6599323B2 (en) * 2000-12-21 2003-07-29 Ethicon, Inc. Reinforced tissue implants and methods of manufacture and use
US6852330B2 (en) * 2000-12-21 2005-02-08 Depuy Mitek, Inc. Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration
CA2365376C (en) * 2000-12-21 2006-03-28 Ethicon, Inc. Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration
US9080146B2 (en) * 2001-01-11 2015-07-14 Celonova Biosciences, Inc. Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with a micro-structured surface
CA2438047A1 (en) * 2001-02-14 2002-08-22 Hildegard M. Kramer Biocompatible fleece for hemostasis and tissue engineering
DE60231862D1 (de) * 2001-02-23 2009-05-20 Genentech Inc Erodierbare polymere zur injektion
US6913765B2 (en) 2001-03-21 2005-07-05 Scimed Life Systems, Inc. Controlling resorption of bioresorbable medical implant material
AU2002256190A1 (en) * 2001-04-16 2002-10-28 Board Of Regents, The University Of Texas System Osteotropic biomaterials, methods of use thereof and implant systems incorporating the same
AU2002308522A1 (en) 2001-05-01 2002-11-11 University Of Southern California Methods for inhibiting tumor cell proliferation
US20030152630A1 (en) * 2001-05-11 2003-08-14 Ng Steven Y. PEG-POE, PEG-POE-PEG, and POE-PEG-POE block copolymers
US6590059B2 (en) * 2001-05-11 2003-07-08 Ap Pharma, Inc. Bioerodible polyorthoesters from dioxolane-based diketene acetals
US7455657B2 (en) * 2001-06-19 2008-11-25 Boston Scientific Scimed, Inc Method and apparatus to modify a fluid using a selectively permeable membrane
WO2003000282A1 (en) * 2001-06-21 2003-01-03 Genentech, Inc. Sustained release formulation
US6730772B2 (en) 2001-06-22 2004-05-04 Venkatram P. Shastri Degradable polymers from derivatized ring-opened epoxides
GB0116341D0 (en) * 2001-07-04 2001-08-29 Smith & Nephew Biodegradable polymer systems
US7345144B2 (en) * 2001-07-11 2008-03-18 Palatin Technologies, Inc. Cyclic peptides for treatment of cachexia
US7342089B2 (en) * 2001-07-11 2008-03-11 Palatin Technologies, Inc. Cyclic peptides for treatment for cachexia
US20030026770A1 (en) * 2001-07-25 2003-02-06 Szymaitis Dennis W. Periodontal regeneration composition and method of using same
US7105182B2 (en) * 2001-07-25 2006-09-12 Szymaitis Dennis W Periodontal regeneration composition and method of using same
US7718802B2 (en) 2001-08-10 2010-05-18 Palatin Technologies, Inc. Substituted melanocortin receptor-specific piperazine compounds
US7655658B2 (en) * 2001-08-10 2010-02-02 Palatin Technologies, Inc. Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds
US7732451B2 (en) * 2001-08-10 2010-06-08 Palatin Technologies, Inc. Naphthalene-containing melanocortin receptor-specific small molecule
EP1425029A4 (en) * 2001-08-10 2006-06-07 Palatin Technologies Inc PEPTIDOMIMETICS OF BIOLOGICALLY ACTIVE METALLOPEPTIDES
US7456184B2 (en) * 2003-05-01 2008-11-25 Palatin Technologies Inc. Melanocortin receptor-specific compounds
US20080063620A1 (en) * 2001-08-13 2008-03-13 Yissum Research Development Company Of The Hebrew University Of Jerusalem Novel reverse thermo-sensitive block copolymers
US20030082235A1 (en) * 2001-08-13 2003-05-01 Yissum Research Development Company Of The Hebrew University Of Jerusalem Novel reverse thermo-sensitive block copolymers
US20030060422A1 (en) 2001-08-31 2003-03-27 Balaji Venkataraman Tannate compositions and methods of treatment
US7081475B2 (en) 2001-09-14 2006-07-25 Prolx Pharmaceuticals Corp. Wortmannin analogs and methods of using same
US7309498B2 (en) * 2001-10-10 2007-12-18 Belenkaya Bronislava G Biodegradable absorbents and methods of preparation
AU2002336694A1 (en) * 2001-11-01 2003-05-12 Lawrence M. Boyd Devices and methods for the restoration of a spinal disc
US7799833B2 (en) * 2001-11-01 2010-09-21 Spine Wave, Inc. System and method for the pretreatment of the endplates of an intervertebral disc
US7488320B2 (en) * 2001-11-01 2009-02-10 Renova Orthopedics, Llc Orthopaedic implant fixation using an in-situ formed anchor
US20070196415A1 (en) * 2002-11-14 2007-08-23 Guohua Chen Depot compositions with multiple drug release rate controls and uses thereof
US20030170289A1 (en) * 2001-11-14 2003-09-11 Guohua Chen Injectable depot compositions and uses thereof
DE60239556D1 (de) * 2001-11-14 2011-05-05 Durect Corp Katheterinjizierbare depotzusammensetzungen und deren verwendung
KR20040065153A (ko) * 2001-11-14 2004-07-21 알자 코포레이션 주입가능한 데포 조성물
US6524606B1 (en) * 2001-11-16 2003-02-25 Ap Pharma, Inc. Bioerodible polyorthoesters containing amine groups
AU2002364193A1 (en) * 2001-12-19 2003-07-09 Advanced Bio Surfaces, Inc. Bone smoothing method and system
AU2003203016A1 (en) * 2002-01-14 2003-07-30 Micro Therapeutics, Inc. Methods for embolizing aneurysmal sites with a high viscosity embolizing composition
US20050058698A1 (en) * 2002-01-21 2005-03-17 Nolan Yvonne Mairead Pharmaceutically acceptable phosphate-glycerol carrying bodies and uses relating to Parkinson's Disease
WO2003061522A2 (en) * 2002-01-22 2003-07-31 Advanced Bio Surfaces, Inc. Interpositional arthroplasty system and method
GB0202233D0 (en) * 2002-01-31 2002-03-20 Smith & Nephew Bioresorbable polymers
US8088388B2 (en) * 2002-02-14 2012-01-03 United Biomedical, Inc. Stabilized synthetic immunogen delivery system
US20030229333A1 (en) * 2002-02-22 2003-12-11 Control Delivery Systems, Inc. Methods for treating otic disorders
US7479535B2 (en) 2002-02-25 2009-01-20 Guilford Pharmaceuticals, Inc. Phosphorous-containing compounds with polymeric chains, and methods of making and using the same
WO2003073912A2 (en) * 2002-02-28 2003-09-12 Wm. Marsh Rice University Pre-fabricated tissue-engineered plug
EP1344538A1 (en) * 2002-03-14 2003-09-17 Degradable Solutions AG Porous biodegradable implant material and method for its fabrication
ES2399880T3 (es) * 2002-03-15 2013-04-04 Cypress Bioscience, Inc. Milnaciprán para el tratamiento del síndrome del intestino irritable
AU2003225516A1 (en) * 2002-03-26 2003-10-08 Yissum Research Development Company Of The Hebrew University Of Jerusalem Responsive biomedical composites
US20030203000A1 (en) * 2002-04-24 2003-10-30 Schwarz Marlene C. Modulation of therapeutic agent release from a polymeric carrier using solvent-based techniques
US20030228365A1 (en) * 2002-06-07 2003-12-11 Fortuna Haviv Pharmaceutical formulation
US7432245B2 (en) * 2002-06-07 2008-10-07 Abbott Laboratories Inc. Pharmaceutical formulation comprising a peptide angiogenesis inhibitor
US20030228366A1 (en) * 2002-06-11 2003-12-11 Chung Shih Reconstitutable compositions of biodegradable block copolymers
US7649023B2 (en) * 2002-06-11 2010-01-19 Novartis Ag Biodegradable block copolymeric compositions for drug delivery
US20030232088A1 (en) * 2002-06-14 2003-12-18 Kimberly-Clark Worldwide, Inc. Materials with both bioadhesive and biodegradable components
US7037983B2 (en) * 2002-06-14 2006-05-02 Kimberly-Clark Worldwide, Inc. Methods of making functional biodegradable polymers
AR039729A1 (es) 2002-06-25 2005-03-09 Alza Corp Formulaciones de deposito de corta duracion
US20040001889A1 (en) 2002-06-25 2004-01-01 Guohua Chen Short duration depot formulations
US20080226723A1 (en) * 2002-07-05 2008-09-18 Celonova Biosciences, Inc. Loadable Polymeric Particles for Therapeutic Use in Erectile Dysfunction and Methods of Preparing and Using the Same
US7160551B2 (en) * 2002-07-09 2007-01-09 The Board Of Trustees Of The University Of Illinois Injectable system for controlled drug delivery
EP1523291B1 (en) * 2002-07-11 2008-06-18 Advanced Bio Surfaces, Inc. Kit for interpositional arthroplasty
DK1380263T3 (da) * 2002-07-12 2007-12-27 Mycrona Ges Fuer Innovative Me Fremgangsmåde og indretning til bestemmelse af et undersögelsesobjekts faktiske position
MXPA05001244A (es) * 2002-07-31 2005-06-08 Alza Corp Composiciones de deposito de polimero multimodal inyectable y usos de las mismas.
AU2002359397B2 (en) * 2002-07-31 2009-01-29 Durect Corporation Injectable depot compositions and uses thereof
US7041111B2 (en) 2002-08-02 2006-05-09 Boston Scientific Scimed, Inc. Placing sutures
US8062573B2 (en) * 2002-09-16 2011-11-22 Theraject, Inc. Solid micro-perforators and methods of use
US7824701B2 (en) 2002-10-18 2010-11-02 Ethicon, Inc. Biocompatible scaffold for ligament or tendon repair
US20040078090A1 (en) 2002-10-18 2004-04-22 Francois Binette Biocompatible scaffolds with tissue fragments
US6800663B2 (en) * 2002-10-18 2004-10-05 Alkermes Controlled Therapeutics Inc. Ii, Crosslinked hydrogel copolymers
US20060003004A1 (en) * 2002-10-25 2006-01-05 Collegium Pharmaceutical, Inc. Pulsatile release compositions of milnacipran
US20040121010A1 (en) * 2002-10-25 2004-06-24 Collegium Pharmaceutical, Inc. Pulsatile release compositions of milnacipran
RU2355385C2 (ru) * 2002-11-06 2009-05-20 Алза Корпорейшн Композиции пролонгированного действия с контролируемым высвобождением
HUE033832T2 (en) 2002-11-15 2018-01-29 Idenix Pharmaceuticals Llc 2'-methyl nucleosides in combination with interferon and Flaviviridae mutation
US20060036158A1 (en) 2003-11-17 2006-02-16 Inrad, Inc. Self-contained, self-piercing, side-expelling marking apparatus
AU2003299659A1 (en) * 2002-12-13 2004-07-09 Durect Corporation Oral drug delivery system comprising high viscosity liquid carrier materials
US20040228830A1 (en) * 2003-01-28 2004-11-18 Collegium Pharmaceutical, Inc. Multiparticulate compositions of milnacipran for oral administration
US20040260398A1 (en) * 2003-02-10 2004-12-23 Kelman David C. Resorbable devices
US20040197301A1 (en) * 2003-02-18 2004-10-07 Zhong Zhao Hybrid polymers and methods of making the same
US20050025707A1 (en) * 2003-02-27 2005-02-03 Patterson William R. Fumed silica embolic compositions
US8197837B2 (en) 2003-03-07 2012-06-12 Depuy Mitek, Inc. Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof
AU2004219595A1 (en) * 2003-03-11 2004-09-23 Qlt Usa Inc. Formulations for cell- schedule dependent anticancer agents
US9445901B2 (en) * 2003-03-12 2016-09-20 Deger C. Tunc Prosthesis with sustained release analgesic
US20060076295A1 (en) 2004-03-15 2006-04-13 The Trustees Of Columbia University In The City Of New York Systems and methods of blood-based therapies having a microfluidic membraneless exchange device
JP4489761B2 (ja) 2003-03-14 2010-06-23 ザ トラスティーズ オブ コロンビア ユニヴァーシティ イン ザ シティ オブ ニューヨーク マイクロ流体無膜交換装置を有する血液ベースの治療のためのシステム及び方法
GB0307011D0 (en) * 2003-03-27 2003-04-30 Regentec Ltd Porous matrix
DE10314082A1 (de) * 2003-03-28 2004-10-21 Mcs Micro Carrier Systems Gmbh Biodegradierbares injizierbares Implantat
US8404269B2 (en) * 2003-04-11 2013-03-26 Michael Snyder Sustained release implantable eye device
US20040202694A1 (en) * 2003-04-11 2004-10-14 Vascular Control Systems, Inc. Embolic occlusion of uterine arteries
US7968548B2 (en) 2003-05-01 2011-06-28 Palatin Technologies, Inc. Melanocortin receptor-specific piperazine compounds with diamine groups
US7727990B2 (en) 2003-05-01 2010-06-01 Palatin Technologies, Inc. Melanocortin receptor-specific piperazine and keto-piperazine compounds
US7727991B2 (en) 2003-05-01 2010-06-01 Palatin Technologies, Inc. Substituted melanocortin receptor-specific single acyl piperazine compounds
EP2860292B1 (en) 2003-05-08 2020-07-22 Tepha, Inc. Polyhydroxyalkanoate medical textiles and fibers
IL155866A0 (en) * 2003-05-12 2003-12-23 Yissum Res Dev Co Responsive polymeric system
US20040247672A1 (en) * 2003-05-16 2004-12-09 Alkermes Controlled Therapeutics, Inc. Injectable sustained release compositions
US7877133B2 (en) * 2003-05-23 2011-01-25 Senorx, Inc. Marker or filler forming fluid
CN1822816A (zh) * 2003-05-30 2006-08-23 阿尔萨公司 可植入的弹性体储库组合物、其用途以及制备方法
US20070184084A1 (en) * 2003-05-30 2007-08-09 Guohua Chen Implantable elastomeric caprolactone depot compositions and uses thereof
US20060188573A1 (en) * 2003-06-10 2006-08-24 Anna Imberg Composite materials and particles
CN1863557B (zh) 2003-06-26 2010-06-16 普西维达公司 原位胶凝的药物递送系统
US8226715B2 (en) 2003-06-30 2012-07-24 Depuy Mitek, Inc. Scaffold for connective tissue repair
US20050025809A1 (en) * 2003-07-08 2005-02-03 Tepha, Inc. Poly-4-hydroxybutyrate matrices for sustained drug delivery
US8343513B2 (en) 2003-07-18 2013-01-01 Oakwood Laboratories, Llc Prevention of molecular weight reduction of the polymer, impurity formation and gelling in polymer compositions
US10583220B2 (en) 2003-08-11 2020-03-10 DePuy Synthes Products, Inc. Method and apparatus for resurfacing an articular surface
AU2004268560B2 (en) * 2003-08-22 2008-08-21 Tepha, Inc. Polyhydroxyalkanoate nerve regeneration devices
US7141354B2 (en) * 2003-09-30 2006-11-28 Dai Nippon Printing Co., Ltd. Photo radical generator, photo sensitive resin composition and article
US7309232B2 (en) * 2003-10-10 2007-12-18 Dentigenix Inc. Methods for treating dental conditions using tissue scaffolds
US20050281879A1 (en) * 2003-11-14 2005-12-22 Guohua Chen Excipients in drug delivery vehicles
US20050107867A1 (en) * 2003-11-17 2005-05-19 Taheri Syde A. Temporary absorbable venous occlusive stent and superficial vein treatment method
US20050273002A1 (en) * 2004-06-04 2005-12-08 Goosen Ryan L Multi-mode imaging marker
US8673021B2 (en) 2003-11-26 2014-03-18 Depuy Mitek, Llc Arthroscopic tissue scaffold delivery device
US7316822B2 (en) 2003-11-26 2008-01-08 Ethicon, Inc. Conformable tissue repair implant capable of injection delivery
US7901461B2 (en) 2003-12-05 2011-03-08 Ethicon, Inc. Viable tissue repair implants and methods of use
GB0329654D0 (en) 2003-12-23 2004-01-28 Smith & Nephew Tunable segmented polyacetal
WO2005067889A1 (en) * 2003-12-30 2005-07-28 Durect Corporation Polymeric implants, preferably containing a mixture of peg and plg, for controlled release of active agents, preferably a gnrh
CN1901931A (zh) * 2004-01-07 2007-01-24 特里梅里斯公司 HIV gp41 HR2－来源的合成肽,及其在抑制人类免疫缺陷性病毒传递的治疗中的用途
JP2007517913A (ja) * 2004-01-13 2007-07-05 バソジェニックス ファーマシューティカルズ， インコーポレイテッド カルシトニン遺伝子関連ペプチドを投与することによって急性心筋梗塞を処置するための方法およびカルシトニン遺伝子関連ペプチドを含有する組成物
US7976847B2 (en) * 2004-01-13 2011-07-12 Vasogenix Pharmaceuticals, Inc. Controlled release CGRP delivery composition for cardiovascular and renal indications
CA2552757A1 (en) * 2004-01-13 2005-08-04 Vasogenix Pharmaceuticals, Inc. Methods of using cgrp for cardiovascular and renal indications
US20050165487A1 (en) 2004-01-28 2005-07-28 Muhanna Nabil L. Artificial intervertebral disc
US11395865B2 (en) 2004-02-09 2022-07-26 DePuy Synthes Products, Inc. Scaffolds with viable tissue
US9238127B2 (en) 2004-02-25 2016-01-19 Femasys Inc. Methods and devices for delivering to conduit
US8048086B2 (en) 2004-02-25 2011-11-01 Femasys Inc. Methods and devices for conduit occlusion
US8052669B2 (en) 2004-02-25 2011-11-08 Femasys Inc. Methods and devices for delivery of compositions to conduits
US8048101B2 (en) 2004-02-25 2011-11-01 Femasys Inc. Methods and devices for conduit occlusion
CA2558200A1 (en) * 2004-03-02 2005-09-15 Nanotherapeutics, Inc. Compositions for repairing bone and methods for preparing and using such compositions
TW200533385A (en) * 2004-03-03 2005-10-16 Commw Scient Ind Res Org Biocompatible polymer compositions for dual or multi staged curing
US20050228433A1 (en) * 2004-03-16 2005-10-13 Weenna Bucay-Couto In situ implant and method of forming same
US20050234336A1 (en) * 2004-03-26 2005-10-20 Beckman Andrew T Apparatus and method for marking tissue
EP1737898A1 (en) * 2004-04-15 2007-01-03 The University of Utah Research Foundation Bioresponsive polymer system for delivery of microbicides
US7709484B1 (en) 2004-04-19 2010-05-04 Palatin Technologies, Inc. Substituted melanocortin receptor-specific piperazine compounds
US8221780B2 (en) 2004-04-20 2012-07-17 Depuy Mitek, Inc. Nonwoven tissue scaffold
US8137686B2 (en) 2004-04-20 2012-03-20 Depuy Mitek, Inc. Nonwoven tissue scaffold
US8657881B2 (en) 2004-04-20 2014-02-25 Depuy Mitek, Llc Meniscal repair scaffold
US8163030B2 (en) * 2004-05-06 2012-04-24 Degradable Solutions Ag Biocompatible bone implant compositions and methods for repairing a bone defect
US20050255045A1 (en) * 2004-05-13 2005-11-17 Woltering Eugene A Surgical marking composition and method
WO2005115489A2 (en) * 2004-05-24 2005-12-08 Genzyme Corporation Adherent polymeric compositions
US8142462B2 (en) 2004-05-28 2012-03-27 Cavitech, Llc Instruments and methods for reducing and stabilizing bone fractures
US7863406B2 (en) * 2004-06-03 2011-01-04 Cornell Research Foundation, Inc. Unsaturated poly(ester-amide) biomaterials
US20110015367A1 (en) * 2004-06-03 2011-01-20 Cornell University Unsaturated poly(ester-amide) and poly(ether ester amide) biomaterials
DE602005008247D1 (de) * 2004-06-04 2008-08-28 Camurus Ab Flüssige depotformulierungen
WO2005120462A2 (en) * 2004-06-07 2005-12-22 Callisyn Pharmaceuticals, Inc. Biodegradable and biocompatible crosslinked polymer hydrogel prepared from pva and/or peg macromer mixtures
EP1604693A1 (en) 2004-06-09 2005-12-14 Scil Technology GmbH In situ forming scaffold, its manufacturing and use
WO2006004774A2 (en) * 2004-06-28 2006-01-12 Stanford University Laulimalide analogues as therapeutic agents
US7556650B2 (en) 2004-06-29 2009-07-07 Spine Wave, Inc. Methods for injecting a curable biomaterial into an intervertebral space
JP4857268B2 (ja) * 2004-06-29 2012-01-18 バイオキュア・インコーポレーテッド 脊椎椎間板髄核移植片
AU2005333515B2 (en) 2004-07-09 2012-05-10 Arizona Board Of Regents, Acting On Behalf Of The University Of Arizona Wortmannin analogs and methods of using same in combination with chemotherapeutic agents
US20060009498A1 (en) * 2004-07-12 2006-01-12 Allergan, Inc. Ophthalmic compositions and methods for treating ophthalmic conditions
ES2293193T5 (es) 2004-07-13 2012-06-13 Bayer Schering Pharma Oy Sistema de suministro retardado con descarga inicial controlada
EP1778305B1 (en) * 2004-08-03 2010-07-07 Tepha, Inc. Non-curling polyhydroxyalkanoate sutures
SI1786400T1 (sl) * 2004-08-12 2009-08-31 Quest Pharmaceutical Services Farmacevtski sestavki za dajanje biološko aktivnih spojin z nadzorovanim sproščanjem
US20060039949A1 (en) * 2004-08-20 2006-02-23 Nycz Jeffrey H Acetabular cup with controlled release of an osteoinductive formulation
WO2006026325A2 (en) * 2004-08-26 2006-03-09 Pathak Chandrashekhar P Implantable tissue compositions and method
WO2006026504A2 (en) * 2004-08-27 2006-03-09 Spherics, Inc. Mucoadhesive oral formulations of high permeability, high solubility drugs
US20060052822A1 (en) * 2004-08-31 2006-03-09 Mirizzi Michael S Apparatus and material composition for permanent occlusion of a hollow anatomical structure
US20060045902A1 (en) * 2004-09-01 2006-03-02 Serbousek Jon C Polymeric wrap for in vivo delivery of osteoinductive formulations
US7754233B2 (en) * 2004-09-03 2010-07-13 Ethicon, Inc. Method of preventing post-operative surgical adhesion
US8440215B2 (en) 2004-09-03 2013-05-14 Ethicon, Inc. Absorbable polymer formulations
US20060057184A1 (en) * 2004-09-16 2006-03-16 Nycz Jeffrey H Process to treat avascular necrosis (AVN) with osteoinductive materials
JP5285275B2 (ja) 2004-09-17 2013-09-11 デュレクト コーポレーション 制御されたデリバリーシステム
US20060074422A1 (en) * 2004-09-27 2006-04-06 Story Brooks J Suture anchor and void filler combination
US9000040B2 (en) 2004-09-28 2015-04-07 Atrium Medical Corporation Cross-linked fatty acid-based biomaterials
US9012506B2 (en) 2004-09-28 2015-04-21 Atrium Medical Corporation Cross-linked fatty acid-based biomaterials
WO2007011385A2 (en) 2004-09-28 2007-01-25 Atrium Medical Corporation Heat cured gel and method of making
US9801982B2 (en) 2004-09-28 2017-10-31 Atrium Medical Corporation Implantable barrier device
WO2006036967A1 (en) 2004-09-28 2006-04-06 Atrium Medical Corporation Solubilizing a drug for use in a coating
CA2582374A1 (en) * 2004-10-04 2006-04-20 Qlt Usa, Inc. Ocular delivery of polymeric delivery formulations
US8313763B2 (en) * 2004-10-04 2012-11-20 Tolmar Therapeutics, Inc. Sustained delivery formulations of rapamycin compounds
US9107850B2 (en) * 2004-10-25 2015-08-18 Celonova Biosciences, Inc. Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US9114162B2 (en) 2004-10-25 2015-08-25 Celonova Biosciences, Inc. Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same
US20210299056A9 (en) 2004-10-25 2021-09-30 Varian Medical Systems, Inc. Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods
CA2584122C (en) 2004-10-25 2013-04-30 Polyzenix Gmbh Loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
RS53890B1 (en) * 2004-11-10 2015-08-31 Tolmar Therapeutics, Inc. STABILIZED POLYMER DELIVERY SYSTEM
AR052155A1 (es) * 2004-12-14 2007-03-07 Novartis Ag Compuestos organicos
EP1827377B1 (en) * 2004-12-14 2008-03-19 Novartis AG In-situ forming implant for animals
US20060282169A1 (en) * 2004-12-17 2006-12-14 Felt Jeffrey C System and method for upper extremity joint arthroplasty
US20060142234A1 (en) * 2004-12-23 2006-06-29 Guohua Chen Injectable non-aqueous suspension
US20060141040A1 (en) * 2004-12-23 2006-06-29 Guohua Chen Injectable non-aqueous suspension
CA2585417A1 (en) * 2005-01-08 2006-07-13 Alphaspine, Inc. Modular disc device
US8470954B2 (en) 2005-01-10 2013-06-25 Ethicon, Inc. Diisocyanate terminated macromer and formulation thereof for use as an internal adhesive or sealant
US20070167617A1 (en) * 2006-01-17 2007-07-19 Fitz Benjamin D Method of making a diisocyanate terminated macromer
US7728097B2 (en) * 2005-01-10 2010-06-01 Ethicon, Inc. Method of making a diisocyanate terminated macromer
US20060153796A1 (en) * 2005-01-10 2006-07-13 Fitz Benjamin D Diisocyanate terminated macromer and formulation thereof for use as an internal adhesive or sealant
US7968668B2 (en) 2005-01-10 2011-06-28 Ethicon Inc. Diisocyanate terminated macromer and formulation thereof for use as an internal adhesive or sealant
EP2206495B1 (en) 2005-01-14 2012-11-21 Camurus AB Topical bioadhesive formulations
US8871712B2 (en) * 2005-01-14 2014-10-28 Camurus Ab Somatostatin analogue formulations
US9649382B2 (en) 2005-01-14 2017-05-16 Camurus Ab Topical bioadhesive formulations
US9060935B2 (en) * 2005-01-21 2015-06-23 Camurus Ab Pharmaceutical lipid compositions
US9017350B2 (en) 2005-01-25 2015-04-28 Covidien Lp Expandable occlusive structure
ATE481088T1 (de) * 2005-01-28 2010-10-15 Tepha Inc Embolisierung unter verwendung von poly-4- hydroxybutyrat-partikeln
US8137664B2 (en) * 2005-02-02 2012-03-20 Sdgi Holdings, Inc. Method and kit for repairing a defect in bone
US7611494B2 (en) 2005-02-08 2009-11-03 Confluent Surgical, Inc. Spray for fluent materials
JP2008530305A (ja) * 2005-02-09 2008-08-07 タイコ ヘルスケア グループ エルピー 合成封止剤
WO2006112941A2 (en) * 2005-02-16 2006-10-26 Cytori Therapeutics, Inc. Resorbable hollow devices for implantation and delivery of therapeutic agents
CA2498623A1 (en) * 2005-02-18 2006-08-18 Qlt Inc. Treatment of onychomycosis
US20060189958A1 (en) * 2005-02-21 2006-08-24 Talton James D Inverted cannula for use in reconstituting dry material in syringes
US7851189B2 (en) * 2005-03-07 2010-12-14 Boston Scientific Scimed, Inc. Microencapsulated compositions for endoluminal tissue engineering
US7591853B2 (en) * 2005-03-09 2009-09-22 Vertebral Technologies, Inc. Rail-based modular disc nucleus prosthesis
US20060222596A1 (en) 2005-04-01 2006-10-05 Trivascular, Inc. Non-degradable, low swelling, water soluble radiopaque hydrogel polymer
US10357328B2 (en) 2005-04-20 2019-07-23 Bard Peripheral Vascular, Inc. and Bard Shannon Limited Marking device with retractable cannula
US20060242562A1 (en) * 2005-04-22 2006-10-26 Microsoft Corporation Embedded method for embedded interaction code array
US8414907B2 (en) 2005-04-28 2013-04-09 Warsaw Orthopedic, Inc. Coatings on medical implants to guide soft tissue healing
US9119901B2 (en) * 2005-04-28 2015-09-01 Warsaw Orthopedic, Inc. Surface treatments for promoting selective tissue attachment to medical impants
WO2006125074A1 (en) * 2005-05-17 2006-11-23 Brown University Research Foundation Drug delivery formulations for targeted delivery
EP1890712A4 (en) * 2005-05-31 2012-08-15 Warsaw Orthopedic Inc COMPOSITIONS AND METHODS FOR TREATING PAIN
US8546326B2 (en) * 2005-06-06 2013-10-01 Camurus Ab Glp-1 analogue formulations
US7727235B2 (en) * 2005-06-29 2010-06-01 Ethicon, Inc. Medical fixation devices with improved torsional drive head
EP1743638A1 (en) 2005-07-15 2007-01-17 Laboratorios Del Dr. Esteve, S.A. Pharmaceutical formulations of substituted pyrazoline compounds
ES2330716B1 (es) * 2005-07-15 2010-07-09 Laboratorios Del Dr.Esteve, S.A. Formulaciones farmaceuticas de compuestos de pirazolina sustituidos.
US20070027105A1 (en) 2005-07-26 2007-02-01 Alza Corporation Peroxide removal from drug delivery vehicle
US20080247987A1 (en) * 2005-08-04 2008-10-09 Angiotech International Ag Block Copolymer Compositions and Uses Thereof
CA2617926A1 (en) 2005-08-08 2007-02-15 Cytyc Corporation Tumescent skin spacing method
EP1922091A2 (en) * 2005-08-18 2008-05-21 Smith & Nephew, PLC High strength devices and composites
US8362086B2 (en) 2005-08-19 2013-01-29 Merial Limited Long acting injectable formulations
GB0517674D0 (en) * 2005-08-31 2005-10-05 Astrazeneca Ab Formulation
GB0517673D0 (en) * 2005-08-31 2005-10-05 Astrazeneca Ab Formulation
US20090035446A1 (en) * 2005-09-06 2009-02-05 Theraject, Inc. Solid Solution Perforator Containing Drug Particle and/or Drug-Adsorbed Particles
US9278161B2 (en) * 2005-09-28 2016-03-08 Atrium Medical Corporation Tissue-separating fatty acid adhesion barrier
US9427423B2 (en) 2009-03-10 2016-08-30 Atrium Medical Corporation Fatty-acid based particles
US8852638B2 (en) 2005-09-30 2014-10-07 Durect Corporation Sustained release small molecule drug formulation
US10174070B2 (en) 2005-09-30 2019-01-08 Endece Llc 6-substituted estradiol derivatives and methods of use
US8052658B2 (en) 2005-10-07 2011-11-08 Bard Peripheral Vascular, Inc. Drug-eluting tissue marker
EP1948043A1 (en) * 2005-10-13 2008-07-30 Endoluminal Therapeutics, Inc. Channeled endomural therapy
KR20140077946A (ko) 2005-10-13 2014-06-24 휴먼 게놈 사이언시즈, 인코포레이티드 자가항체 양성 질환 환자의 치료에 유용한 방법 및 조성물
WO2007047781A2 (en) 2005-10-15 2007-04-26 Atrium Medical Corporation Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings
US20070100449A1 (en) * 2005-10-31 2007-05-03 O'neil Michael Injectable soft tissue fixation technique
EP1948810A4 (en) * 2005-11-04 2010-06-30 Biosyntech Canada Inc COMPOSITION AND METHOD USING CHITOSAN FOR THE EFFICIENT ADMINISTRATION OF NUCLEIC ACIDS TO CELLS
US20070110788A1 (en) * 2005-11-14 2007-05-17 Hissong James B Injectable formulation capable of forming a drug-releasing device
US7754826B1 (en) * 2005-11-15 2010-07-13 Clemson University Copolymers from lactide
WO2007061896A1 (en) 2005-11-17 2007-05-31 Zogenix, Inc. Delivery of viscous formulations by needle-free injection
US20070149641A1 (en) * 2005-12-28 2007-06-28 Goupil Dennis W Injectable bone cement
CN101400363B (zh) * 2006-01-18 2012-08-29 昌达生物科技公司 具有增强的稳定性的药物组合物
EP1989220B1 (en) 2006-02-02 2011-12-14 Trimeris, Inc. Hiv fusion inhibitor peptides with improved biological properties
US8673398B2 (en) * 2006-02-23 2014-03-18 Meadwestvaco Corporation Method for treating a substrate
US9849216B2 (en) 2006-03-03 2017-12-26 Smith & Nephew, Inc. Systems and methods for delivering a medicament
US8795709B2 (en) * 2006-03-29 2014-08-05 Incept Llc Superabsorbent, freeze dried hydrogels for medical applications
JP2009532385A (ja) * 2006-03-30 2009-09-10 パラティン・テクノロジーズ・インコーポレーテッド 線状ナトリウム利尿ペプチド構築物
US8580746B2 (en) 2006-03-30 2013-11-12 Palatin Technologies, Inc. Amide linkage cyclic natriuretic peptide constructs
US7622440B2 (en) * 2006-03-30 2009-11-24 Palatin Technologies, Inc. Cyclic natriuretic peptide constructs
US9017361B2 (en) 2006-04-20 2015-04-28 Covidien Lp Occlusive implant and methods for hollow anatomical structure
US7976873B2 (en) * 2006-05-10 2011-07-12 Medtronic Xomed, Inc. Extracellular polysaccharide solvating system for treatment of bacterial ear conditions
US7959943B2 (en) * 2006-05-10 2011-06-14 Medtronics Xomed, Inc. Solvating system and sealant for medical use in the middle or inner ear
US7993675B2 (en) 2006-05-10 2011-08-09 Medtronic Xomed, Inc. Solvating system and sealant for medical use in the sinuses and nasal passages
WO2007137245A2 (en) 2006-05-22 2007-11-29 Columbia University Systems and methods of microfluidic membraneless exchange using filtration of extraction fluid outlet streams
US7872068B2 (en) * 2006-05-30 2011-01-18 Incept Llc Materials formable in situ within a medical device
EP1872807A1 (en) * 2006-06-30 2008-01-02 Scil Technology GmbH Biomaterial containing degradation stabilized polymer
BRPI0715469A2 (pt) 2006-07-11 2013-03-12 Qps Llc composiÇÕes farmacÊuticas para a liberaÇço sustentada de peptÍdeos
EP3009477B1 (en) 2006-07-20 2024-01-24 Orbusneich Medical Pte. Ltd Bioabsorbable polymeric composition for a medical device
US7945307B2 (en) * 2006-08-04 2011-05-17 Senorx, Inc. Marker delivery system with obturator
US20090171198A1 (en) * 2006-08-04 2009-07-02 Jones Michael L Powdered marker
US7947758B2 (en) * 2006-08-09 2011-05-24 Ethicon, Inc. Moisture activated latent curing adhesive or sealant
US8129445B2 (en) * 2006-08-09 2012-03-06 Ethicon, Inc. Moisture activated latent curing adhesive or sealant
US7834017B2 (en) 2006-08-11 2010-11-16 Palatin Technologies, Inc. Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents
US20080058954A1 (en) * 2006-08-22 2008-03-06 Hai Trieu Methods of treating spinal injuries using injectable flowable compositions comprising organic materials
US9744137B2 (en) * 2006-08-31 2017-08-29 Supernus Pharmaceuticals, Inc. Topiramate compositions and methods of enhancing its bioavailability
US8076448B2 (en) * 2006-10-11 2011-12-13 Tolmar Therapeutics, Inc. Preparation of biodegradable polyesters with low-burst properties by supercritical fluid extraction
US7959942B2 (en) 2006-10-20 2011-06-14 Orbusneich Medical, Inc. Bioabsorbable medical device with coating
CN101631513B (zh) 2006-10-20 2013-06-05 奥巴斯尼茨医学公司 可生物吸收的聚合物组合物和医疗设备
EP2079385B1 (en) 2006-10-23 2013-11-20 C.R.Bard, Inc. Breast marker
US8268347B1 (en) 2006-10-24 2012-09-18 Aradigm Corporation Dual action, inhaled formulations providing both an immediate and sustained release profile
US20080102097A1 (en) * 2006-10-31 2008-05-01 Zanella John M Device and method for treating osteolysis using a drug depot to deliver an anti-inflammatory agent
AU2007325918B2 (en) 2006-11-03 2013-10-17 Durect Corporation Transdermal delivery systems comprising bupivacaine
US9492596B2 (en) 2006-11-06 2016-11-15 Atrium Medical Corporation Barrier layer with underlying medical device and one or more reinforcing support structures
EP2083875B1 (en) 2006-11-06 2013-03-27 Atrium Medical Corporation Coated surgical mesh
EP1973528B1 (en) 2006-11-17 2012-11-07 Supernus Pharmaceuticals, Inc. Sustained-release formulations of topiramate
US9737414B2 (en) 2006-11-21 2017-08-22 Vertebral Technologies, Inc. Methods and apparatus for minimally invasive modular interbody fusion devices
CN102274552B (zh) 2006-11-30 2017-03-01 史密夫和内修有限公司 纤维增强的复合材料
US7943683B2 (en) * 2006-12-01 2011-05-17 Tepha, Inc. Medical devices containing oriented films of poly-4-hydroxybutyrate and copolymers
WO2008073965A2 (en) 2006-12-12 2008-06-19 C.R. Bard Inc. Multiple imaging mode tissue marker
US20080140106A1 (en) * 2006-12-12 2008-06-12 Kimberly-Clark Worldwide, Inc. Enhanced cuff sealing for endotracheal tubes
WO2008076973A2 (en) 2006-12-18 2008-06-26 C.R.Bard Inc. Biopsy marker with in situ-generated imaging properties
US8088095B2 (en) * 2007-02-08 2012-01-03 Medtronic Xomed, Inc. Polymeric sealant for medical use
PT2115029E (pt) 2007-02-15 2015-10-26 Tolmar Therapeutics Inc Poli-(lactido/glicolido) de efeito de libertação imediata reduzido e métodos de produção de polímeros
US20090227981A1 (en) * 2007-03-05 2009-09-10 Bennett Steven L Low-Swelling Biocompatible Hydrogels
US20090227689A1 (en) 2007-03-05 2009-09-10 Bennett Steven L Low-Swelling Biocompatible Hydrogels
US20080220047A1 (en) 2007-03-05 2008-09-11 Sawhney Amarpreet S Low-swelling biocompatible hydrogels
US20090068243A1 (en) * 2007-04-03 2009-03-12 Brian Bray Novel formulations for delivery of antiviral peptide therapeutics
AU2008240418B2 (en) * 2007-04-18 2013-08-15 Smith & Nephew Plc Expansion moulding of shape memory polymers
ATE547129T1 (de) 2007-04-19 2012-03-15 Smith & Nephew Inc Multimodale formgedächtnis-polymere
EP2150288B1 (en) * 2007-04-19 2011-04-13 Smith & Nephew, Inc. Graft fixation
CA2684759C (en) 2007-05-15 2015-11-03 Barry M. Fell Surgically implantable knee prosthesis with captured keel
HUE030789T2 (en) 2007-05-18 2017-06-28 Durect Corp Improved depot formulation
CA2692002A1 (en) 2007-05-21 2008-11-27 Aoi Medical Inc. Articulating cavitation device
BRPI0811319A2 (pt) 2007-05-25 2015-02-10 Tolmar Therapeutics Inc Composição fluida, método de formação de uma composição fluida, implante biodegrádavel formado in situ, método de formação de um implante biodegradável in situ, kit, implante e método de trataento
CN201075472Y (zh) * 2007-05-28 2008-06-18 富士康(昆山)电脑接插件有限公司 电连接器
US20100204432A1 (en) * 2007-05-28 2010-08-12 Husam Younes Biodegradable elastomers prepared by the condensation of an organic di-, tri- or tetra-carboxylic acid and an organic diol
GB0711656D0 (en) * 2007-06-15 2007-07-25 Camurus Ab Formulations
US9125807B2 (en) 2007-07-09 2015-09-08 Incept Llc Adhesive hydrogels for ophthalmic drug delivery
US20090149569A1 (en) * 2007-07-19 2009-06-11 Shastri V Prasad Surface engineering of tissue graft materials for enhanced porosity and cell adhesion
US7850453B2 (en) * 2007-08-08 2010-12-14 Coll Partners Ltd. Reshapable device for fixation at a dental site
US8067028B2 (en) * 2007-08-13 2011-11-29 Confluent Surgical Inc. Drug delivery device
GB0716385D0 (en) 2007-08-22 2007-10-03 Camurus Ab Formulations
WO2009035571A2 (en) * 2007-09-07 2009-03-19 Qlt Plug Delivery, Inc Lacrimal implant detection
CA2700354A1 (en) * 2007-09-25 2009-04-02 Trimeris, Inc. Novel methods of synthesis for therapeutic antiviral peptides
US20090088723A1 (en) * 2007-09-28 2009-04-02 Accessclosure, Inc. Apparatus and methods for treating pseudoaneurysms
US8703119B2 (en) * 2007-10-05 2014-04-22 Polygene Ltd. Injectable biodegradable polymer compositions for soft tissue repair and augmentation
EP2886105B1 (en) 2007-10-24 2018-12-05 Camurus Ab Controlled-release formulations
US20090110738A1 (en) * 2007-10-26 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Particles for Cosmetic and Reconstructive Tissue Augmentation Applications and Methods of Preparing and Using the Same
US20090111763A1 (en) * 2007-10-26 2009-04-30 Celonova Biosciences, Inc. Loadable polymeric particles for bone augmentation and methods of preparing and using the same
US20090110730A1 (en) * 2007-10-30 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Particles for Marking or Masking Individuals and Methods of Preparing and Using the Same
US20090110731A1 (en) * 2007-10-30 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Microparticles for Therapeutic Use in Alopecia and Methods of Preparing and Using the Same
JP2011503183A (ja) * 2007-11-13 2011-01-27 サーモディクス ファーマシューティカルズ， インコーポレイテッド 薬物送達のプラットホームとしての粘稠なターポリマー
AT506168B1 (de) * 2007-11-23 2012-02-15 Univ Wien Tech Verwendung von zusammensetzungen zur herstellung biologisch abbaubarer, bioverträglicher, vernetzter polymere auf basis von polyvinylalkohol
JP2011506318A (ja) * 2007-12-06 2011-03-03 デュレクト コーポレーション 経口医薬製剤
CA2710515A1 (en) * 2007-12-28 2009-07-09 Khashayar Kevin Neshat Controlled release local anesthetic for post dental surgery and method of use
US20090181068A1 (en) * 2008-01-14 2009-07-16 Dunn Richard L Low Viscosity Liquid Polymeric Delivery System
EP2262891B1 (en) 2008-01-30 2022-09-21 Histogen, Inc. Extracellular matrix compositions
US8311610B2 (en) * 2008-01-31 2012-11-13 C. R. Bard, Inc. Biopsy tissue marker
AU2009212396A1 (en) 2008-02-04 2009-08-13 The Trustees Of Columbia University In The City Of New York Fluid separation devices, systems and methods
WO2009100422A2 (en) * 2008-02-08 2009-08-13 Zimmer, Inc. Drug delivery system comprising microparticles and gelation system
US9107815B2 (en) * 2008-02-22 2015-08-18 Allergan, Inc. Sustained release poloxamer containing pharmaceutical compositions
US8071663B2 (en) * 2008-02-29 2011-12-06 Ethicon, Inc. Medically acceptable formulation of a diisocyanate terminated macromer for use as an internal adhesive or sealant
US8324292B2 (en) * 2008-02-29 2012-12-04 Ethicon, Inc. Medically acceptable formulation of a diisocyanate terminated macromer for use as an internal adhesive or sealant
US8745133B2 (en) * 2008-03-28 2014-06-03 Yahoo! Inc. System and method for optimizing the storage of data
US11969501B2 (en) 2008-04-21 2024-04-30 Dompé Farmaceutici S.P.A. Auris formulations for treating otic diseases and conditions
CN104491864A (zh) 2008-04-21 2015-04-08 奥德纳米有限公司 用于治疗耳部疾病和病况的耳用调配物及方法
JP2011518881A (ja) 2008-04-28 2011-06-30 ゾゲニクス インコーポレーティッド 片頭痛の治療のための製剤
US20110125158A1 (en) * 2008-05-01 2011-05-26 Ashish Dhar Diwan Systems, methods and apparatuses for formation and insertion of tissue prostheses
CN102026623B (zh) 2008-05-14 2013-08-14 奥德纳米有限公司 用于治疗耳部病症的控制释放皮质类固醇组合物和方法
AU2009249610B2 (en) * 2008-05-21 2014-01-16 Theraject, Inc. Method of manufacturing solid solution perforator patches and uses thereof
WO2009148579A2 (en) 2008-06-03 2009-12-10 Qlt Usa, Inc. Dehydrated hydrogel inclusion complex of a bioactive agent with flowable drug delivery system
US8877225B2 (en) * 2008-06-03 2014-11-04 Tolmar Therapeutics, Inc. Controlled release copolymer formulation with improved release kinetics
RU2513142C2 (ru) 2008-06-12 2014-04-20 Медтроник Ксомед Инк. Способ лечения хронических ран
MX2011000629A (es) 2008-07-17 2011-04-26 Merial Ltd Formulaciones analgesicas inyectables de larga duracion para animales.
US8784870B2 (en) * 2008-07-21 2014-07-22 Otonomy, Inc. Controlled release compositions for modulating free-radical induced damage and methods of use thereof
EP2306975A4 (en) 2008-07-21 2012-10-31 Otonomy Inc CONTROLLED RELEASE COMPOSITIONS MODULATING THE OTIC STRUCTURE AND MODULATING THE NATURAL IMMUNE SYSTEM AND METHODS OF TREATING OTIC DISORDERS
US8318817B2 (en) 2008-07-21 2012-11-27 Otonomy, Inc. Controlled release antimicrobial compositions and methods for the treatment of otic disorders
CN103751842A (zh) 2008-07-30 2014-04-30 米辛瑟斯有限公司 衍生自前胃胞外基质的组织支架
US9271706B2 (en) * 2008-08-12 2016-03-01 Covidien Lp Medical device for wound closure and method of use
EP2444116B1 (en) 2008-08-19 2016-01-06 Covidien LP Detachable tip microcatheter
GB0815435D0 (en) 2008-08-22 2008-10-01 Camurus Ab Formulations
US9327061B2 (en) 2008-09-23 2016-05-03 Senorx, Inc. Porous bioabsorbable implant
WO2010038239A2 (en) * 2008-09-26 2010-04-08 Saumya Sharma Pharmaceutical composition comprising coenzyme q10
US10070888B2 (en) 2008-10-03 2018-09-11 Femasys, Inc. Methods and devices for sonographic imaging
US9554826B2 (en) 2008-10-03 2017-01-31 Femasys, Inc. Contrast agent injection system for sonographic imaging
US9889230B2 (en) * 2008-10-17 2018-02-13 Covidien Lp Hemostatic implant
US20100260844A1 (en) 2008-11-03 2010-10-14 Scicinski Jan J Oral pharmaceutical dosage forms
DK2362866T3 (en) 2008-11-11 2015-10-12 Signum Biosciences Inc Isoprenylforbindelser and their methods
US8822546B2 (en) * 2008-12-01 2014-09-02 Medtronic, Inc. Flowable pharmaceutical depot
WO2010065799A2 (en) 2008-12-04 2010-06-10 Palatin Technologies, Inc. Amine substituted piperidine melanocortin receptor-specific compounds
WO2010065802A2 (en) 2008-12-04 2010-06-10 Palatin Technologies, Inc. Substituted pyrrolidine or imidazolidine melanocortin receptor-specific compounds
WO2010065801A1 (en) 2008-12-04 2010-06-10 Palatin Technologies, Inc. Amine substituted piperazine melanocortin receptor-specific compounds
US9415197B2 (en) * 2008-12-23 2016-08-16 Surmodics, Inc. Implantable suction cup composites and implants comprising same
US8974808B2 (en) 2008-12-23 2015-03-10 Surmodics, Inc. Elastic implantable composites and implants comprising same
US20100168807A1 (en) * 2008-12-23 2010-07-01 Burton Kevin W Bioactive terpolymer compositions and methods of making and using same
US9480643B2 (en) 2008-12-23 2016-11-01 Surmodics Pharmaceuticals, Inc. Implantable composites and implants comprising same
US8951546B2 (en) 2008-12-23 2015-02-10 Surmodics Pharmaceuticals, Inc. Flexible implantable composites and implants comprising same
US8670818B2 (en) 2008-12-30 2014-03-11 C. R. Bard, Inc. Marker delivery device for tissue marker placement
US8469779B1 (en) 2009-01-02 2013-06-25 Lifecell Corporation Method for debristling animal skin
WO2010079340A2 (en) 2009-01-08 2010-07-15 Eisai R & D Management Co., Ltd. Assay
EP2210589B1 (en) 2009-01-22 2015-05-06 Ludwig-Maximilians-Universität München Vesicular phospholipid gels comprising proteinaceous substances
US20100204570A1 (en) * 2009-02-06 2010-08-12 Paul Lubock Anchor markers
US8409606B2 (en) * 2009-02-12 2013-04-02 Incept, Llc Drug delivery through hydrogel plugs
US20110014190A1 (en) 2009-02-12 2011-01-20 Human Genome Sciences, Inc. Use of b lymphocyte stimulator protein antagonists to promote transplantation tolerance
WO2010094032A2 (en) 2009-02-16 2010-08-19 Aoi Medical Inc. Trauma nail accumulator
EP2223707B1 (de) * 2009-02-26 2014-04-09 New Dent AG Implantatsystem und Knochenimplantat
US8383140B2 (en) 2009-04-03 2013-02-26 Poly-Med, Inc. Absorbable crystalline copolyester-based bioactive hydroforming luminal liner compositions
US9433700B2 (en) 2009-04-27 2016-09-06 Medibeacon Inc. Tissue sealant compositions, vascular closure devices, and uses thereof
EP2427233B1 (en) * 2009-05-04 2016-12-21 Incept Llc Biomaterials for track and puncture closure
CN102458436B (zh) 2009-06-08 2015-06-03 帕拉丁科技公司 黑皮质素受体特异性肽
WO2011005939A2 (en) 2009-07-09 2011-01-13 Mayo Foundation For Medical Education And Research Long acting atrial natriuretic peptide (la-anp) and methods for use thereof
US20110015672A1 (en) * 2009-07-17 2011-01-20 Tyco Healthcare Group Lp Method for Coating a Medical Device
US9200112B2 (en) 2009-08-10 2015-12-01 Ethicon, Inc. Semi-crystalline, fast absorbing polymer formulation
US20110038910A1 (en) 2009-08-11 2011-02-17 Atrium Medical Corporation Anti-infective antimicrobial-containing biomaterials
FR2949687B1 (fr) 2009-09-04 2011-09-23 Sofradim Production Tissu avec picots revetus d'un materiau hydrosoluble
US8470355B2 (en) * 2009-10-01 2013-06-25 Covidien Lp Mesh implant
US8138236B2 (en) * 2009-10-29 2012-03-20 Ethicon, Inc. Solvent-free moisture activated latent curing surgical adhesive or sealant
US9044524B2 (en) * 2009-10-30 2015-06-02 Ethicon, Inc. Absorbable polyethylene diglycolate copolymers to reduce microbial adhesion to medical devices and implants
CA2780294C (en) 2009-11-09 2018-01-16 Spotlight Technology Partners Llc Polysaccharide based hydrogels
WO2011057133A1 (en) 2009-11-09 2011-05-12 Spotlight Technology Partners Llc Fragmented hydrogels
PL2498603T3 (pl) 2009-11-12 2017-03-31 Signum Biosciences, Inc. Zastosowanie środków przeciwbakteryjnych do leczenia chorób związanych z nabłonkiem
EP3960215A1 (en) * 2009-12-15 2022-03-02 Incept, LLC Implants and biodegradable fiducial markers
GB0922438D0 (en) 2009-12-22 2010-02-03 Ucl Business Plc Agents having tissue generative activity
US20110218606A1 (en) * 2010-03-02 2011-09-08 Medtronic Vascular, Inc. Methods for Stabilizing Femoral Vessels
US20120130489A1 (en) * 2010-05-19 2012-05-24 Chernomorsky Ary S Methods and apparatus for in situ formation of surgical implants
JP5894146B2 (ja) 2010-05-20 2016-03-23 エコラボ ユーエスエー インコーポレイティド レオロジー改変された低発泡性液体抗菌組成物及びその使用方法
US10350159B2 (en) 2010-05-31 2019-07-16 Laboratories Farmacéuticos Rovi, S.A. Paliperidone implant formulation
US10335366B2 (en) 2010-05-31 2019-07-02 Laboratorios Farmacéuticos Rovi, S.A. Risperidone or paliperidone implant formulation
US10285936B2 (en) 2010-05-31 2019-05-14 Laboratorios Farmacéuticos Rovi, S.A. Injectable composition with aromatase inhibitor
US10881605B2 (en) 2010-05-31 2021-01-05 Laboratorios Farmaceuticos Rovi, S.A. Methods for the preparation of injectable depot compositions
US10463607B2 (en) 2010-05-31 2019-11-05 Laboratorios Farmaceutics Rofi S.A. Antipsychotic Injectable Depot Composition
PT2394663T (pt) 2010-05-31 2021-11-26 Farm Rovi Lab Sa Composições para implantes biodegradáveis injectáveis
DK2394664T3 (en) 2010-05-31 2016-09-12 Laboratorios Farmacéuticos Rovi S A Antipsychotic injectable depot composition
GB2513267B (en) 2010-06-08 2015-03-18 Rb Pharmaceuticals Ltd Injectable flowable composition comprising buprenorphine
US9272044B2 (en) 2010-06-08 2016-03-01 Indivior Uk Limited Injectable flowable composition buprenorphine
GB2513060B (en) 2010-06-08 2015-01-07 Rb Pharmaceuticals Ltd Microparticle buprenorphine suspension
US9364518B2 (en) 2010-06-24 2016-06-14 Torrent Pharmaceuticals Limited Pharmaceutical composition containing goserelin for in-situ implant
US9232805B2 (en) 2010-06-29 2016-01-12 Biocure, Inc. In-situ forming hydrogel wound dressings containing antimicrobial agents
EP2593141B1 (en) 2010-07-16 2018-07-04 Atrium Medical Corporation Composition and methods for altering the rate of hydrolysis of cured oil-based materials
WO2012030819A1 (en) 2010-08-30 2012-03-08 Surmodics Pharmaceuticals, Inc. Terpolymers as pressure-sensitive adhesives
US8961501B2 (en) 2010-09-17 2015-02-24 Incept, Llc Method for applying flowable hydrogels to a cornea
GB201016436D0 (en) 2010-09-30 2010-11-17 Q Chip Ltd Method of making solid beads
GB201016433D0 (en) 2010-09-30 2010-11-17 Q Chip Ltd Apparatus and method for making solid beads
US11291483B2 (en) 2010-10-20 2022-04-05 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US11207109B2 (en) 2010-10-20 2021-12-28 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US11058796B2 (en) 2010-10-20 2021-07-13 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
WO2015095745A1 (en) 2010-10-20 2015-06-25 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US20120101593A1 (en) * 2010-10-20 2012-04-26 BIOS2 Medical, Inc. Implantable polymer for bone and vascular lesions
US9320601B2 (en) 2011-10-20 2016-04-26 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US11484627B2 (en) 2010-10-20 2022-11-01 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US10525169B2 (en) 2010-10-20 2020-01-07 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US8740982B2 (en) * 2010-10-26 2014-06-03 Kyphon Sarl Devices containing a chemonucleolysis agent and methods for treating an intervertebral disc or spinal arachnoiditis
US9414930B2 (en) * 2010-10-26 2016-08-16 Kyphon SÀRL Activatable devices containing a chemonucleolysis agent
LT2658525T (lt) 2010-12-29 2017-12-11 Medincell Biologiškai skaidomos vaistų tiekimo kompozicijos
US9084602B2 (en) 2011-01-26 2015-07-21 Covidien Lp Buttress film with hemostatic action for surgical stapling apparatus
JP6150734B2 (ja) 2011-02-03 2017-06-21 アレクシオン ファーマシューティカルズ， インコーポレイテッド 同種移植片の生存を長期化するための抗ｃｄ２００抗体の使用
WO2012142419A1 (en) 2011-04-14 2012-10-18 Lifecell Corporation Regenerative materials
US20130040923A1 (en) 2011-05-13 2013-02-14 Trimel Pharmaceuticals Corporation Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
AR082266A1 (es) 2011-05-13 2012-11-28 Univ Nac Del Litoral Microparticula inyectable de liberacion controlada
US9757388B2 (en) 2011-05-13 2017-09-12 Acerus Pharmaceuticals Srl Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels
US20130045958A1 (en) 2011-05-13 2013-02-21 Trimel Pharmaceuticals Corporation Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
WO2012177759A1 (en) 2011-06-20 2012-12-27 Rdc Holdings, Llc System and method for repairing joints
US8998925B2 (en) 2011-06-20 2015-04-07 Rdc Holdings, Llc Fixation system for orthopedic devices
WO2013003157A1 (en) 2011-06-28 2013-01-03 Yale University Cell-free tissued engineered vascular grafts
US9089523B2 (en) 2011-07-28 2015-07-28 Lifecell Corporation Natural tissue scaffolds as tissue fillers
KR20140059249A (ko) 2011-08-30 2014-05-15 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 나트륨이뇨 폴리펩티드
US10226417B2 (en) 2011-09-16 2019-03-12 Peter Jarrett Drug delivery systems and applications
DE102011114986A1 (de) * 2011-09-28 2013-03-28 Ethris Gmbh Sprühsystem
US8586527B2 (en) 2011-10-20 2013-11-19 Jaipal Singh Cerivastatin to treat pulmonary disorders
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
CA2856520C (en) 2011-11-23 2021-04-06 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
CN104185420B (zh) 2011-11-30 2017-06-09 埃默里大学 用于治疗或预防逆转录病毒和其它病毒感染的抗病毒jak抑制剂
CN109200013A (zh) 2011-12-05 2019-01-15 因赛普特有限责任公司 医用有机凝胶方法和组合物
BR112014013691A2 (pt) 2011-12-05 2017-06-13 Camurus Ab pré-formulação, métodos para distribuição de um agente ativo de peptídeo, para a preparação de uma composição cristalina líquida, de tratamento ou profilaxia de um sujeito, processo para a formação de uma pré-formulação, uso de uma mistura cristalina não líquida de baixa viscosidade, dispositivo de administração de pré-preenchido, e, kit
US9115066B2 (en) 2011-12-14 2015-08-25 Indicator Systems International, Inc. Trisubstituted methyl alcohols and their polymerizable derivatives
US9549805B2 (en) 2011-12-20 2017-01-24 Lifecell Corporation Flowable tissue products
ES2864104T3 (es) 2011-12-20 2021-10-13 Lifecell Corp Productos tisulares laminados
WO2013103896A1 (en) 2012-01-06 2013-07-11 Mayo Foundation For Medical Education And Research Treating cardiovascular or renal diseases
LT2806877T (lt) 2012-01-23 2019-12-10 Sage Therapeutics Inc Neuroaktyvios steroidų kompozicijos, apimančios alopregnanolono ir sulfobutilo eterio beta-ciklodekstrino kompleksą
DK2806907T3 (en) 2012-01-24 2019-02-18 Lifecell Corp EXTENDED TISSUE MATRIX
US9534018B2 (en) 2012-03-13 2017-01-03 Tensive Controls Inc. Melanocortin analogs having enhanced activity and transport
US9510953B2 (en) 2012-03-16 2016-12-06 Vertebral Technologies, Inc. Modular segmented disc nucleus implant
US8403927B1 (en) 2012-04-05 2013-03-26 William Bruce Shingleton Vasectomy devices and methods
US8753643B1 (en) 2012-04-11 2014-06-17 Life-Science Innovations, Llc Spray dried compositions and methods of use
US9782436B2 (en) 2012-04-24 2017-10-10 Lifecell Corporation Flowable tissue matrices
NL2008861C2 (en) * 2012-05-23 2013-11-26 Urogyn B V Composition for soft tissue treatment.
SG11201407678YA (en) 2012-05-25 2014-12-30 Camurus Ab Somatostatin receptor agonist formulations
EP2861580B1 (en) 2012-06-07 2018-04-25 Georgia State University Research Foundation, Inc. Seca inhibitors and methods of making and using thereof
US9867880B2 (en) 2012-06-13 2018-01-16 Atrium Medical Corporation Cured oil-hydrogel biomaterial compositions for controlled drug delivery
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US20130338122A1 (en) 2012-06-18 2013-12-19 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US20150196640A1 (en) 2012-06-18 2015-07-16 Therapeuticsmd, Inc. Progesterone formulations having a desirable pk profile
BR112015000547B1 (pt) 2012-07-13 2020-11-10 Lifecell Corporation método para tratar tecido
WO2014016428A1 (en) 2012-07-26 2014-01-30 Camurus Ab Opioid formulations
IL275725B (en) 2012-08-21 2022-08-01 Sage Therapeutics Inc Treatment methods for epilepsy and status epilepticus
AU2013323747B2 (en) 2012-09-26 2017-02-02 Lifecell Corporation Processed adipose tissue
LT2900230T (lt) 2012-09-27 2019-01-10 The Children`S Medical Center Corporation Junginiai, skirti nutukimo gydymui ir jų panaudojimo būdai
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US10568891B2 (en) 2012-12-21 2020-02-25 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
ES2781578T3 (es) 2013-02-06 2020-09-03 Lifecell Corp Métodos para la modificación localizada de productos tisulares
US20140308352A1 (en) 2013-03-11 2014-10-16 Zogenix Inc. Compositions and methods involving polymer, solvent, and high viscosity liquid carrier material
BR112015022023B1 (pt) 2013-03-11 2022-12-06 Durect Corporation Composição de liberação controlada injetável compreendendo transportador líquido de alta viscosidade
US10624865B2 (en) 2013-03-14 2020-04-21 Pathak Holdings Llc Methods, compositions, and devices for drug/live cell microarrays
US11744838B2 (en) 2013-03-15 2023-09-05 Acerus Biopharma Inc. Methods of treating hypogonadism with transnasal testosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event
CA2905131A1 (en) 2013-03-15 2014-09-18 Durect Corporation Compositions with a rheological modifier to reduce dissolution variability
US10226552B2 (en) 2013-04-04 2019-03-12 Arizona Board Of Regents On Behalf Of The Unviersity Of Arizona Materials, systems, devices, and methods for endoluminal electropolymeric paving and sealing
JP2016525379A (ja) * 2013-05-23 2016-08-25 ２０６ オーソ，インコーポレーテッド 複合材インプラントの提供および使用を含む、骨折を治療するための、ならびに／または、骨を補強および／もしくは増強するための方法および装置
MX2016002408A (es) 2013-08-27 2016-10-28 Otonomy Inc Metodos para el tratamiento de trastornos oticos pediatricos.
USD715942S1 (en) 2013-09-24 2014-10-21 C. R. Bard, Inc. Tissue marker for intracorporeal site identification
USD715442S1 (en) 2013-09-24 2014-10-14 C. R. Bard, Inc. Tissue marker for intracorporeal site identification
USD716450S1 (en) 2013-09-24 2014-10-28 C. R. Bard, Inc. Tissue marker for intracorporeal site identification
USD716451S1 (en) 2013-09-24 2014-10-28 C. R. Bard, Inc. Tissue marker for intracorporeal site identification
US9757330B2 (en) 2013-10-18 2017-09-12 Industrial Technology Research Institute Recipe for in-situ gel, and implant, drug delivery system formed thereby
US9668844B2 (en) 2013-11-06 2017-06-06 Colldent Y.A Ltd Device for fixation at a dental site
TR201901299T4 (tr) 2013-11-26 2019-02-21 Childrens Medical Ct Corp Obezite tedavisine yönelik bileşikler ve bunların kullanım yöntemleri.
EP3079668A1 (en) 2013-12-09 2016-10-19 Durect Corporation Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same
JP6247400B2 (ja) * 2013-12-31 2017-12-13 ペベエベ・エスア 身体再建及び身体成形における使用のための制御放出脂肪酸組成物
GB201404139D0 (en) 2014-03-10 2014-04-23 Rb Pharmaceuticals Ltd Sustained release buprenorphine solution formulations
WO2015138919A1 (en) 2014-03-14 2015-09-17 The University Of North Carolina At Chapel Hill Small molecules for inhibiting male fertility
US20170209408A1 (en) 2014-04-03 2017-07-27 The Children's Medical Center Corporation Hsp90 inhibitors for the treatment of obesity and methods of use thereof
AU2015264003A1 (en) 2014-05-22 2016-11-17 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US11266395B2 (en) 2014-06-17 2022-03-08 Ganihand, LLC Devices and methods to provide hands free scleral depression during ophthalmic procedures
US9421199B2 (en) 2014-06-24 2016-08-23 Sydnexis, Inc. Ophthalmic composition
WO2016172712A2 (en) 2015-04-23 2016-10-27 Sydnexis, Inc. Ophthalmic composition
EP3164115A4 (en) 2014-07-03 2017-05-17 Otonomy, Inc. Sterilization of ciprofloxacin composition
ES2807178T3 (es) 2014-08-15 2021-02-22 Tepha Inc Suturas de autorretención de poli-4-hidroxibutirato y copolímeros del mismo
US11382909B2 (en) 2014-09-05 2022-07-12 Sydnexis, Inc. Ophthalmic composition
WO2016044683A1 (en) 2014-09-19 2016-03-24 Tensive Controls, Inc. Anti-microbial peptides
WO2016057796A1 (en) 2014-10-08 2016-04-14 The Arizona Board Of Regents On Behalf Of The University Of Arizona Flowable electronics
US20160106804A1 (en) 2014-10-15 2016-04-21 Yuhua Li Pharmaceutical composition with improved stability
US10550187B2 (en) 2014-10-24 2020-02-04 Incept, Llc Extra luminal scaffold
WO2016071767A1 (en) 2014-11-07 2016-05-12 Indivior Uk Limited Buprenorphine dosing regimens
AU2015360469B2 (en) 2014-12-10 2021-03-25 Incept, Llc Hydrogel drug delivery implants
US10626521B2 (en) 2014-12-11 2020-04-21 Tepha, Inc. Methods of manufacturing mesh sutures from poly-4-hydroxybutyrate and copolymers thereof
CA2969429C (en) 2014-12-11 2020-10-27 Tepha, Inc. Methods of orienting multifilament yarn and monofilaments of poly-4-hydroxybutyrate and copolymers thereof
US11382731B2 (en) 2015-02-27 2022-07-12 Covidien Lp Medical devices with sealing properties
WO2016168388A2 (en) 2015-04-14 2016-10-20 Palatin Technologies, Inc. Therapies for obesity, diabetes and related indications
US11369591B2 (en) 2015-05-12 2022-06-28 Incept, Llc Drug delivery from hydrogels
WO2016196367A1 (en) 2015-05-29 2016-12-08 Sydnexis, Inc. D2o stabilized pharmaceutical formulations
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
CA2993645A1 (en) 2015-07-28 2017-02-02 Otonomy, Inc. Trkb or trkc agonist compositions and methods for the treatment of otic conditions
EP3331495B1 (en) 2015-08-03 2020-11-04 Tolmar International Limited Liquid polymer delivery system for extended administration of drugs
JP6835841B2 (ja) 2015-11-16 2021-02-24 エボニック オペレーションズ ゲーエムベーハー 非核酸系逆転写酵素阻害剤とポリ（ラクチド−ｃｏ−グリコリド）とを含む注射液
HRP20231453T1 (hr) 2015-11-16 2024-03-01 Medincell S.A. Postupak za morseliranje i/ili usmjeravanje farmaceutski aktivnih sastojaka na sinovijalno tkivo
AU2016361579B2 (en) 2015-11-25 2022-08-04 Incept, Llc Shape changing drug delivery devices and methods
WO2017100576A1 (en) 2015-12-11 2017-06-15 Otonomy, Inc. Ciprofloxacin otic composition and kits and method for using same
WO2017173044A1 (en) 2016-04-01 2017-10-05 Therapeuticsmd Inc. Steroid hormone compositions in medium chain oils
CA3020153A1 (en) 2016-04-01 2017-10-05 Therapeuticsmd, Inc. Steroid hormone pharmaceutical composition
EP3463500A1 (en) 2016-06-03 2019-04-10 LifeCell Corporation Methods for localized modification of tissue products
US10925837B2 (en) 2016-08-26 2021-02-23 Akina, Inc. Biodegradable polymer formulations for extended efficacy of botulinum toxin
EP3512513A4 (en) 2016-09-16 2020-04-15 Otonomy, Inc. GEL FORMULA FOR THE EAR FOR TREATING OTITIS EXTERNA
US11439587B2 (en) 2016-09-22 2022-09-13 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Injectable implants
JP7430529B2 (ja) 2016-09-23 2024-02-13 インセプト・リミテッド・ライアビリティ・カンパニー 前房内薬物送達デポ
WO2018089601A1 (en) 2016-11-09 2018-05-17 Mayo Foundation For Medical Education And Research Manp analogues
WO2018111949A1 (en) * 2016-12-12 2018-06-21 Neuronoff, Inc. Electrode curable and moldable to contours of a target in bodily tissue and methods of manufacturing and placement and dispensers therefor
US11992482B2 (en) 2016-12-21 2024-05-28 Rilento Pharma, Llc Malleable controlled release local anesthetic with hemostatic composition
EP3558405A1 (en) 2016-12-22 2019-10-30 LifeCell Corporation Devices and methods for tissue cryomilling
DK3576771T3 (da) 2017-01-31 2022-05-30 Veru Inc Sammensætninger og fremgangsmåder til langvarig frigivelse af antagonister for gonadotropin-frigivende hormon (gnrh)
US10646484B2 (en) 2017-06-16 2020-05-12 Indivior Uk Limited Methods to treat opioid use disorder
WO2019051477A1 (en) 2017-09-11 2019-03-14 Sage Therapeutics, Inc. METHODS OF TREATING EPILEPSY OR EPILEPTIC MALE CONDITION
AU2018351051A1 (en) 2017-10-18 2020-03-19 Lifecell Corporation Adipose tissue products and methods of production
US11123375B2 (en) 2017-10-18 2021-09-21 Lifecell Corporation Methods of treating tissue voids following removal of implantable infusion ports using adipose tissue products
US11246994B2 (en) 2017-10-19 2022-02-15 Lifecell Corporation Methods for introduction of flowable acellular tissue matrix products into a hand
ES2960617T3 (es) 2017-10-19 2024-03-05 Lifecell Corp Productos de matriz de tejido acelular fluida y métodos de producción
CN111278386A (zh) * 2017-10-23 2020-06-12 恩朵罗杰克斯股份有限公司 腔内装置和聚合物
AU2018371787A1 (en) 2017-11-21 2020-11-05 Sydnexis, Inc. Ophthalmic composition and delivery device thereof
WO2019125358A1 (en) 2017-12-18 2019-06-27 Foresee Pharmaceuticals Pharmaceutical compositions having a selected release duration
WO2019154895A1 (en) 2018-02-08 2019-08-15 Strekin Ag Gel formulation for preventing or treating hearing loss
CA3106231A1 (en) 2018-07-09 2020-01-16 Regeneron Pharmaceuticals, Inc. Tuning of release kinetics in hydrogels
UY38386A (es) 2018-09-25 2020-04-30 Tolmar Int Ltd Sistema de suministro de polímero líquido para la administración prolongada de fármacos
EP3946547A4 (en) 2019-03-26 2023-01-18 Pocket Naloxone Corp. DEVICES AND METHODS FOR DELIVERING PHARMACEUTICAL COMPOSITIONS
JP2022535694A (ja) 2019-05-27 2022-08-10 トルマー インターナショナル リミテッド 乳がんを処置するためのリュープロリド酢酸塩組成物およびその使用方法
BR112021024043A2 (pt) 2019-05-30 2022-02-08 Lifecell Corp Implante mamário biológico
AU2020302924A1 (en) 2019-06-27 2022-02-17 Layerbio, Inc. Ocular device delivery methods and systems
GB201910895D0 (en) * 2019-07-31 2019-09-11 Univ Birmingham Curable monomers and compositions
AU2020342591A1 (en) 2019-09-02 2022-03-03 Camurus Ab Formulations and treatment methods
JP2022551818A (ja) 2019-09-30 2022-12-14 トルマー インターナショナル リミテッド 活性医薬成分としてのペプチドの延長送達のための液体ポリマー組成物およびシステム
IL292008A (en) 2019-10-07 2022-06-01 Oak Crest Inst Of Science Oral missile drug delivery device
AU2020391230A1 (en) 2019-11-27 2022-06-09 Oak Crest Institute Of Science Sustained release drug delivery device
KR20220140711A (ko) 2020-01-13 2022-10-18 듀렉트 코퍼레이션 불순물이 감소된 지속 방출 약물 전달 시스템 및 관련 방법
US11633405B2 (en) 2020-02-07 2023-04-25 Therapeuticsmd, Inc. Steroid hormone pharmaceutical formulations
US11278709B1 (en) 2021-03-12 2022-03-22 Pocket Naloxone Corp. Drug delivery device and methods for using same
EP4362932A1 (en) * 2021-06-30 2024-05-08 The University of North Carolina at Chapel Hill Injectable, biodegradable and removable polymer based drug suspension for ultra-long-acting drug delivery
TW202313047A (zh) 2021-09-21 2023-04-01 西班牙商禾霏藥品實驗室有限公司 抗精神病可注射儲積型組合物
CN114404659B (zh) * 2021-12-06 2022-09-16 中国科学院长春应用化学研究所 一种管状材料、其制备方法及其应用
WO2023133517A1 (en) 2022-01-06 2023-07-13 Oak Crest Institute Of Science Subdermal implant for sustained drug delivery
WO2024003291A1 (en) 2022-06-30 2024-01-04 Virbac Deslorelin use in chemical castration of a non-human mammal related to pk/pd interaction
US20240139187A1 (en) 2022-10-12 2024-05-02 The Children's Medical Center Corporation Selective hypothalamus permeable hdac6 inhibitors for treatment of leptin-resistant obesity

Family Cites Families (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2155658A (en) * 1936-01-08 1939-04-25 Chemische Forschungs Gmbh Surgical and medical preparations
NL109113C (ko) * 1957-03-27
US3328246A (en) * 1957-08-20 1967-06-27 Bicrex Lab Ltd Dental compositions and methods of making same
US3218283A (en) * 1962-07-26 1965-11-16 Monsanto Co Novel solutions of poly-(acrylic anhydride) and poly-(methacrylic anhydride) polymers
US3219527A (en) * 1963-06-17 1965-11-23 Loyola University Peridontal pack or dressing composition
US3463158A (en) * 1963-10-31 1969-08-26 American Cyanamid Co Polyglycolic acid prosthetic devices
US3520949A (en) * 1966-07-26 1970-07-21 Nat Patent Dev Corp Hydrophilic polymers,articles and methods of making same
US3887699A (en) * 1969-03-24 1975-06-03 Seymour Yolles Biodegradable polymeric article for dispensing drugs
US3767784A (en) * 1970-12-01 1973-10-23 S Gluck Composition for the protection and treatment of injured body tissue and method of utilizing the same
US3760034A (en) * 1971-01-26 1973-09-18 Union Carbide Corp Graft copolymers of lactone polyesters
US3755558A (en) * 1971-02-23 1973-08-28 Du Pont Polylactide drug mixtures for topical application atelet aggregation
US3696811A (en) * 1971-06-17 1972-10-10 Squibb & Sons Inc Periodontal bandage and backing therefor
US4450150A (en) * 1973-05-17 1984-05-22 Arthur D. Little, Inc. Biodegradable, implantable drug delivery depots, and method for preparing and using the same
US3939111A (en) * 1974-07-01 1976-02-17 The B. F. Goodrich Company Stable polyurethane solutions
US3935308A (en) * 1974-08-08 1976-01-27 The United States Of America As Represented By The Secretary Of The Navy Wound covering and method of application
US3931678A (en) * 1974-09-24 1976-01-13 Loctite (Ireland) Limited Dental filling method and composition formed thereby
CH625702A5 (ko) * 1977-01-18 1981-10-15 Delalande Sa
US4148871A (en) * 1977-10-11 1979-04-10 Pitt Colin G Sustained subdermal delivery ofdrugs using poly(ε-caprolactone) and its copolymers
DE2917037C2 (de) * 1979-04-27 1980-12-11 Josef Dipl.-Chem. Dr. 8000 Muenchen Gaensheimer Parenteral arzneimittelhaltige partiell resorbierbare Mehrkomponentenmasse auf Basis von polymeren Stoffen
US4408023A (en) * 1980-11-12 1983-10-04 Tyndale Plains-Hunter, Ltd. Polyurethane diacrylate compositions useful for contact lenses and the like
JPS57110254A (en) * 1980-12-29 1982-07-09 Teijin Ltd Coating agent of injured membrane part of oral cavity
US4793336A (en) * 1981-03-25 1988-12-27 Wang Paul Y Wound coverings and processes for their preparation
US4447562A (en) * 1981-07-15 1984-05-08 Ivani Edward J Amino-polysaccharides and copolymers thereof for contact lenses and ophthalmic compositions
US4582640A (en) * 1982-03-08 1986-04-15 Collagen Corporation Injectable cross-linked collagen implant material
US4570629A (en) * 1982-03-17 1986-02-18 University Of Illinois Foundation Hydrophilic biopolymeric copolyelectrolytes, and biodegradable wound dressing comprising same
EP0092329B1 (en) * 1982-04-07 1988-07-27 Bernard Paul Philippe Feinmann Improved material and method for dentistry
CA1211266A (en) * 1982-11-12 1986-09-16 Alfred E. Lauchenauer Shaped semi-solid articles
US4443430A (en) * 1982-11-16 1984-04-17 Ethicon, Inc. Synthetic absorbable hemostatic agent
US4439420A (en) * 1982-11-16 1984-03-27 Ethicon, Inc. Absorbable hemostatic composition
US5286763A (en) * 1983-03-22 1994-02-15 Massachusetts Institute Of Technology Bioerodible polymers for drug delivery in bone
US4631188A (en) * 1983-08-31 1986-12-23 S.K.Y. Polymers, Ltd. (Kingston Technologies) Injectable physiologically-acceptable polymeric composition
DE3486088T2 (de) * 1983-08-31 1993-09-30 Sky Polymers Einspritzbare physiologisch unbedenkliche polymerzusammensetzungen.
GR80494B (en) * 1983-10-07 1985-02-04 Forsyth Dental Infirmary Intra-pocket drug delivery devices for treatment of periodontal diseases
EP0501523B1 (en) * 1983-11-14 1997-04-09 Columbia Laboratories, Inc. Bioadhesive compositions
EP0159293A1 (fr) * 1984-04-02 1985-10-23 Battelle Memorial Institute Matière polymérique filmogène utilisable comme pansement et sa fabrication
US4663077A (en) * 1984-06-11 1987-05-05 Morton Thiokol Inc. Microbiocidal compositions comprising an aryl alkanol and a microbiocidal compound dissolved therein
GB8416234D0 (en) * 1984-06-26 1984-08-01 Ici Plc Biodegradable amphipathic copolymers
ATE128715T1 (de) * 1984-07-16 1995-10-15 Celtrix Pharma Polypeptide induzierende faktoren in knochen und knorpel.
US4595713A (en) * 1985-01-22 1986-06-17 Hexcel Corporation Medical putty for tissue augmentation
US4650665A (en) * 1985-02-08 1987-03-17 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
US4568536A (en) * 1985-02-08 1986-02-04 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
US4772470A (en) * 1985-04-27 1988-09-20 Nitto Electric Industrial Co., Ltd. Oral bandage and oral preparations
US4767627A (en) * 1985-05-29 1988-08-30 Merck & Co., Inc. Drug delivery device which can be retained in the stomach for a controlled period of time
US4702917A (en) * 1985-11-18 1987-10-27 Research Triangle Institute Porous bioabsorbable polyesters
US4767861A (en) * 1986-01-28 1988-08-30 Vipont Laboratories Recovery of benzo-c-phenanthridine alkaloids
US4774227A (en) * 1986-02-14 1988-09-27 Collagen Corporation Collagen compositions for bone repair containing autogeneic marrow
JPS62223112A (ja) * 1986-03-25 1987-10-01 Rooto Seiyaku Kk 歯周病治療剤
US4780320A (en) * 1986-04-29 1988-10-25 Pharmetrix Corp. Controlled release drug delivery system for the periodontal pocket
US4857602A (en) * 1986-09-05 1989-08-15 American Cyanamid Company Bioabsorbable surgical suture coating
US4846165A (en) * 1986-11-26 1989-07-11 Dentsply Research & Development Corp. Wound dressing membrane
JPH0649735B2 (ja) * 1986-11-29 1994-06-29 住友化学工業株式会社 新規エチレン共重合体およびその製造方法
US4800219A (en) * 1986-12-22 1989-01-24 E. I. Du Pont De Nemours And Company Polylactide compositions
US4981696A (en) * 1986-12-22 1991-01-01 E. I. Du Pont De Nemours And Company Polylactide compositions
US4983689A (en) * 1987-05-07 1991-01-08 Yu Simon H Process for making macromolecular monomers of polylactones with terminal acryloyl unsaturation and block copolymers thereof
US5013553A (en) * 1987-06-30 1991-05-07 Vipont Pharmaceutical, Inc. Drug delivery devices
US4804691A (en) * 1987-08-28 1989-02-14 Richards Medical Company Method for making a biodegradable adhesive for soft living tissue
US4920203A (en) * 1987-12-17 1990-04-24 Allied-Signal Inc. Medical devices fabricated from homopolymers and copolymers having recurring carbonate units
US4938763B1 (en) * 1988-10-03 1995-07-04 Atrix Lab Inc Biodegradable in-situ forming implants and method of producing the same
US5324520A (en) * 1988-12-19 1994-06-28 Vipont Pharmaceutical, Inc. Intragingival delivery systems for treatment of periodontal disease
US5007940A (en) * 1989-06-09 1991-04-16 American Medical Systems, Inc. Injectable polymeric bodies
US5324519A (en) * 1989-07-24 1994-06-28 Atrix Laboratories, Inc. Biodegradable polymer composition
US5077049A (en) * 1989-07-24 1991-12-31 Vipont Pharmaceutical, Inc. Biodegradable system for regenerating the periodontium
US5487897A (en) * 1989-07-24 1996-01-30 Atrix Laboratories, Inc. Biodegradable implant precursor
AU2605592A (en) * 1991-10-15 1993-04-22 Atrix Laboratories, Inc. Polymeric compositions useful as controlled release implants
EP0560014A1 (en) * 1992-03-12 1993-09-15 Atrix Laboratories, Inc. Biodegradable film dressing and method for its formation
WO1995028124A2 (en) * 1994-04-08 1995-10-26 Atrix Laboratories, Inc. An adjunctive polymer system for use with medical device

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JPH04503163A (ja) 1992-06-11
NO911277D0 (no) 1991-04-02
IL91850A (en) 1995-03-30
DK57291D0 (da) 1991-04-02
LU91193I2 (fr) 2005-10-25
NO2005021I1 (no) 2005-10-03
NO304413B1 (no) 1998-12-14
ATE228861T1 (de) 2002-12-15
ZA897511B (en) 1991-06-26
DE122004000029I1 (de) 2004-11-18
US5340849A (en) 1994-08-23
DE68927956D1 (de) 1997-05-15
CA1340694C (en) 1999-08-03
AU5067793A (en) 1994-02-17
EP0436667A4 (en) 1991-10-16
US5278202A (en) 1994-01-11
US4938763A (en) 1990-07-03
US5278201A (en) 1994-01-11
HK1005012A1 (en) 1998-12-18
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US5733950A (en) 1998-03-31
US5739176A (en) 1998-04-14
AU666050B2 (en) 1996-01-25
WO1990003768A1 (en) 1990-04-19
DE68929441T2 (de) 2003-09-25
NO911277L (no) 1991-05-31
US4938763B1 (en) 1995-07-04
DE68929441D1 (de) 2003-01-16
EP0436667A1 (en) 1991-07-17
KR920700017A (ko) 1992-02-19
EP0773034A1 (en) 1997-05-14
JP2992046B2 (ja) 1999-12-20
EP0773034B1 (en) 2002-12-04
DE68927956T2 (de) 1997-07-17
US5990194A (en) 1999-11-23
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DK57291A (da) 1991-06-03
DK175906B1 (da) 2005-06-06
ATE151257T1 (de) 1997-04-15
EP0436667B1 (en) 1997-04-09

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