CN101801521A - 生物膜中细菌细胞内的生理学分散响应诱导 - Google Patents

生物膜中细菌细胞内的生理学分散响应诱导 Download PDF

Info

Publication number
CN101801521A
CN101801521A CN200880024691A CN200880024691A CN101801521A CN 101801521 A CN101801521 A CN 101801521A CN 200880024691 A CN200880024691 A CN 200880024691A CN 200880024691 A CN200880024691 A CN 200880024691A CN 101801521 A CN101801521 A CN 101801521A
Authority
CN
China
Prior art keywords
derivant
composition
dispersion
biomembrane
solution
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN200880024691A
Other languages
English (en)
Other versions
CN101801521B (zh
Inventor
D·G·达维斯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Research Foundation of State University of New York
Original Assignee
Research Foundation of State University of New York
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40122044&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN101801521(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Research Foundation of State University of New York filed Critical Research Foundation of State University of New York
Publication of CN101801521A publication Critical patent/CN101801521A/zh
Application granted granted Critical
Publication of CN101801521B publication Critical patent/CN101801521B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/12—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electromagnetic waves
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
    • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
    • G02B1/041—Lenses
    • G02B1/043—Contact lenses

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Dentistry (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • Emergency Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Electromagnetism (AREA)
  • Toxicology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)

Abstract

本发明的一个方面涉及组合物。该组合物包括分散诱导剂，该分散诱导剂包含：H3C-(CH2)n-CHm CHmR，其中是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。该组合物还包含添加剂组分，该添加剂组分选自以下组分中的一种或多种：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。将该组合物配制成使其当与由微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，该分散诱导剂选择性地作用于微生物并具有合适的生物反应，而不需要对所述基质直接作用，以将该生物膜分散。本发明也涉及使用该化合物的方法。

Description

生物膜中细菌细胞内的生理学分散响应诱导
本申请要求2007年5月14日提交的美国临时专利申请序号60/917,791和2008年1月2日提交的61/018,639的权益，这两个专利申请均通过引用而整体结合到本文中。
本发明在由NIH和NSF给予的授予编号为NSFMCB-0321672和NIH R15AI055521-01的政府资助下完成。因此本发明中政府拥有某些权利。
发明领域
本发明涉及在生物膜中诱导细菌细胞内的生理学分散响应的方法。
发明背景
由于生物膜结构的致密性质、生物膜细菌的假定的复位的生理状态和由生物膜基质聚合物给予的保护，天然和人造化学试剂不能充分地攻击和破坏有传染性的生物膜群体(Costerton等，″在自然界和疾病中的细菌生物膜″，Annu.Rev.Microbiol.41：435-464(1987)；Hoiby等，″对细菌生物膜的免疫反应″，In Microbial Biofilms，Lappin-Scott等编辑，Cambridge：Cambridge University Press(1995))。增强的抗生素抗性是与生物膜细菌有关的一般特征。当粘附时，细菌显示极强的抗性，使生物膜细胞对各种抗微生物药物的敏感度比悬浮(自由漂浮)培养生长的同样细菌低10-1000倍。例如，被认为是最有效的抗菌剂之一的氧化性生物杀灭剂-氯(作为次氯酸钠)，已经显示当与同种悬浮细胞比较时，杀灭金黄色葡萄球菌(Staphylococcus aureus)的生物膜细胞的浓度需要增加600倍(Luppens等，″评估金黄色葡萄球菌(Staphylococcus aureus)生物膜细胞对消毒剂的抗性的标准试验的开发″，Appl Environ Microbiol.68：4194-200(2002))。已经提出了解释生物膜细菌对抗生素的非常抗性的几种假设，包括：(i)减慢生物膜细菌(尤其是深入生物膜内的那些细菌)显示的代谢和分裂速率；(ii)生物膜EPS基质可用作吸附剂或反应物，减少可利用与生物膜细胞相互作用的试剂的量。此外，生物膜结构可通过阻挡进入生物膜区域而在物理上减少抗微生物药物的渗透；(iii)生物膜细胞在生理上与悬浮细菌不同，表达特异性的保护因子例如多药物外排泵和应力响应调节子(Brown等，″细菌生物膜对抗生素的抗性：生长速率相关的效应？″J.Antimicrob.Chemotherapy 22：777-783(1988)；Anwar等，″老化生物膜的建立：细菌抵抗抗菌治疗的可能机制″，Antimicrob.AgentsChemother.36：1347-1351(1992)；Mah等，″生物膜对抗微生物药物抗性的机制″，Trends Microbiol.9：34-39(2001)；Sauer等，″铜绿假单胞菌(Pseudomonas aeruginosa)在发育期间显示多个表型作为生物膜″，J.Bacteriol.184：1140-1154(2002)；Stewart，P.S.，″细菌生物膜的抗生素抗药机制″，Int.J.Med.Microbiol.292：107-113(2002)；Donlan等，″生物膜：临床相关微生物的存活机制″，Clinical Microbiol.Reviews 15：167-193(2002)；Gilbert等，″微生物生物膜群落的生理和集体对抗″，Adv.Microb.Physiol.46：202-256(2002)；Gilbert等，″体外和体内的生物膜：单一机制暗示交叉抗药吗？″J.Appl.Microbiol.Suppl.98S-110S(2002))。如详细的分子研究所显示的，显然这些因子中的每一个在生物膜对抗微生物药物的不寻常的抗药中起作用。初始治疗通常对仅在生物膜微集落的边缘杀灭细菌有效。深陷于这些微集落中的细菌不受抗生素影响并形成连续传播感染的胞窝。
由于它们对抗有效的治疗，因此在感染中和在工业系统中微生物生物膜存在显著的问题。
分离是用于描述细胞(单个地或成组地)从生物膜或基质去除的一般性术语。Bryers，J.D.，″模拟生物膜积聚″，在：PhysiologyModels in Microbiology。Bazin等编辑，Boca Raton，FL.，第2卷，第109-144页(1988)分成细菌从生物膜分离的四种不同分离机制。它们是：磨损、轻檫、侵蚀和蜕落。已经主要从作用于生物膜细菌的化学和物理环境的观点来描述这些机制。许多作者已经暗示活性分离作为生理学上调节的事件，但很少进行研究以显示细菌从生物膜分离的生物学基础。
由Peyton等，″微生物生物膜和生物膜反应器″，BioprocessTechnol.20：187-231(1995)对铜绿假单胞菌(P.aeruginosa)进行了对分离的生理调节的一项研究。在他们的研究工作中，观察到底物限制致使分离速率降低，大概降低生长速率的结果。Allison等，″胞外产物作为荧光假单胞菌(Pseudomonas fluorescens)生物膜形成和分离的介体″，FEMS Microbiol.Lett.167：179-184(1998)显示，在延长的温育之后，荧光假单胞菌(P.fluorescens)生物膜进行分离，同时EPS减少。在热纤维梭菌(Clostridium thermocellum)中，稳定期的发病已经与增强从基质分离有关(Lamed等，″经过广泛的表面细胞器在热纤维梭菌(Clostridium thermocellum)中接触和分解纤维素(Cellulolysis)″，Experientia 42：72-73(1986))。已经假定饥饿可通过未知的机制导致分离，允许细菌寻找更富于营养素的栖息地(O′Toole等，″当微生物发育时形成生物膜″，Ann.Rev.Microbiol.54：49-79(2000))。
许多实验室已经观察到从流动系统转变成分批培养系统导致生物膜分离。一个实验室已经观察到，当在连续培养系统中停止流动时铜绿假单胞菌(P.aeruginosa)的生物膜细胞的可重复的分离(Davies，D.G.，″在生物膜形成和分散中基质聚合物的调节″，在Microbial Extracellular Polymeric Substances，第93-112页，Wingender等编辑，Berlin：Springer(1999))。
其它的已经提出降解酶的释放。用其30产生表面蛋白释放酶(SPRE)的革兰氏阳性生物体变形链球菌(Streptococcus mutans)发现了一个这样的实例，显示介导从细胞被膜释放蛋白质(Lee等，″变形链球菌(Streptococcus mutans)生物膜细胞通过内源性酶活性的分离″，Infect.Immun.64：1035-1038(1996))。Boyd等，″海藻酸裂解酶在铜绿假单胞菌(Pseudomonas aeruginosa)的细胞分离中的作用″，Appl Environ.Microbiol.60：2355-2359(1995)显示海藻酸裂解酶的过表达引起海藻酸盐的降解。当诱导铜绿假单胞菌(P.aeruginosa)的粘液型菌株过表达海藻酸裂解酶时，通过轻洗更容易的从固体培养基除去细胞。
细胞密度依赖性调节也可对酶的释放起作用，该酶可以降解生物膜基质聚合物，允许细菌从生物膜分散。在the Center for BiofilmEngineering at Montana State University，USA(Davies，D.G.和Costerton，J.W.)中和在University of Exeter，UK，Lapin-Scott博士的实验室中，已经观察到当某些细菌(包括铜绿假单胞菌(P.aeruginosa))在生物膜细胞簇中达到高细胞密度时，细菌经常经历分离事件。缺乏合成群体感应自体诱导剂3OC12-HSL的能力的铜绿假单胞菌(P.aeruginosa)突变体，在用温和的去污剂处理后对分离敏感(Davies等，″在细菌生物膜的发育中涉及细胞-细胞信号″，Science 280：295-298(1998))。其它研究者已经证明，高丝氨酸内酯可在分离中起作用。Lynch等，″在不锈钢上形成的嗜水气单胞菌(Aeromonas hydrohila)生物膜中群体感应的研究：In：Biofilms-The Good，the Bad and the Ugly，Wimpenny等编辑。Bioline，Cardiff，第209-223页(1999)报导了增强嗜水气单胞菌(Aeromonashydrophila)从生物膜的分离，和Puckas等，″在自由营生光合作用细菌球形红细菌(Rhodobacter sphaeroides)中的群体感应系统″J.Bacteriol.179：7530-7537(1997)报导了高丝氨酸内酯的生成与在球形红细菌(Rhodobacter sphaeroides)中的细胞簇形成成负相关。
已经认识到铜绿假单胞菌(P.aeruginosa)生物膜在分批培养瓶中(在玻璃液体界面)不发育成宏观的生物膜结构。然而，当培养基连续地通过这样的烧瓶泵送时，(因为在恒化器中)放纵的生物膜发育完全覆盖玻璃表面。当在这样的系统中停止流动时，生物膜在许多天一般约72小时之后脱落(Davies等，″在细菌生物膜的发育中涉及细胞-细胞信号″，Science 280：295-298(1998))。已经从大量革兰氏阴性细菌和革兰氏阳性细菌以及细菌的混合培养物观察到生物膜不能在分批培养中发育。该现象证明分批生长的一些方面抑制生物膜发育。
在生物膜发育的末期期间，细菌的蛋白质图比前期、表示成熟II的生物膜细菌更充分地匹配悬浮细胞的蛋白质图(见本申请的图3，和Sauer等，″铜绿假单胞菌(Pseudomonas aeruginosa)在作为生物膜发育期间显示多个表型″，J.Bacteriol.184：1140-1154(2002))。
由于生物膜结构的致密性质、生物膜细菌的假定降低的生理状态和生物膜基质聚合物给予的保护，目前天然和人造化学试剂不能充分地攻击和破坏有传染性的生物膜群体(Costerton等，″在自然界和疾病中的细菌生物膜″，Annu.Rev.Microbiol.41：435-464(1987)；Hoiby等，″对细菌生物膜的免疫反应″，In Microbial Biofilms，Lappin-Scott等编辑，Cambridge：Cambridge University Press(1995))。
本发明涉及克服了本领域中这些和其他不足之处。
发明概述
本发明的一个方面涉及一种组合物。该组合物包含具有下式的一种或多种分散诱导剂：
Figure G2008800246911D00051
其中
Figure G2008800246911D00052
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体(biostere)。该组合物还包含选自以下的一种或多种添加剂组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。将所述组合物配制成使其当与由微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，所述分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应，以将该生物膜分散。
本发明的另一个方面涉及一种治疗或预防受试者中由生物膜介导的病症的方法。该方法包括提供具有或易感生物膜介导的病症的受试者，该生物膜由微生物产生，因此生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予受试者，该分散诱导剂包含：其中
Figure G2008800246911D00062
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。结果，治疗或预防了所述受试者中由生物膜介导的病症。
本发明的又一个方面涉及一种处理或抑制表面上生物膜形成的方法。该方法包括提供具有或易感生物膜形成的表面，该生物膜由微生物产生，其中该生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予表面，该分散诱导剂包含：
Figure G2008800246911D00063
其中
Figure G2008800246911D00064
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。结果，处理或抑制了表面上生物膜的形成。
本申请的另一个方面涉及一种溶液，该溶液包含具有下式的分散诱导剂：其中
Figure G2008800246911D00066
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸，其中所述诱导剂以小于0.5％重量的浓度存在，且其中所述溶液的pH大于5。
本发明的又一个方面涉及一种组合物，该组合物包含选自以下组分中一种或多种的组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。此外，该组合物包括分散诱导剂，该分散诱导剂包含：
Figure G2008800246911D00071
其中
Figure G2008800246911D00072
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸。将诱导剂配制成非盐形式。
本发明也涉及包括2-癸烯酸顺式异构体的溶液，其中该溶液选自皮肤软膏剂、牙膏和漱口剂，且其中该溶液基本上不含2-癸烯酸反式异构体。
本申请的另一种形式涉及包含2-癸烯酸顺式异构体的溶液，其中该溶液选自皮肤软膏剂、牙膏和漱口剂，且其中所述溶液不含反式异构体。
本申请的另一种形式是一种方法，该方法包括提供接触透镜和含浓度小于0.5％重量的分散诱导剂的溶液，所述诱导剂包含：
Figure G2008800246911D00073
其中
Figure G2008800246911D00074
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。然后用所述溶液处理接触透镜。
本发明的还一种形式是一种方法，该方法包括提供有皮肤病的受试者和pH大于5的溶液，其中所述溶液包含浓度小于0.5％重量的分散诱导剂，所述诱导剂包含：其中
Figure G2008800246911D00076
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。然后用该溶液治疗皮肤病。
本发明的又一些方面涉及一些方法，此类方法治疗烧伤的受试者；治疗和/或预防牙斑、龋齿、齿龈疾病和口腔感染；清洁和/或消毒接触透镜；在受试者的皮肤上治疗和/或预防痤疮或其它生物膜相关的皮肤感染和在受试者中治疗和/或预防慢性生物膜相关疾病。此类方法涉及在对分别完成各任务有效的条件下，给予本发明的分散诱导剂。生物膜分散诱导剂有利地对生物膜内的微生物具有高度的生物活性，因此，药学上可接受的制剂不必对破坏基质直接有化学或机械活性。因此，所述组合物可具有温和的pH，且是非刺激性的。
本发明也涉及一种组合物，该组合物包含一种或多种分散诱导剂和一种或多种添加剂组分。这些添加剂组分选自生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。将所述组合物配制成使其当与由微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，所述分散诱导剂不需要直接作用，而选择性地作用于所述微生物并具有合适的生物反应，以使所述基质破坏。
本发明的另一个方面涉及一种治疗或预防受试者中由生物膜介导的病症的方法。该方法包括提供具有或易感生物膜介导的病症的受试者，该生物膜由微生物产生，因此生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予受试者，因此治疗或预防了受试者中由生物膜介导的病症。
本申请的又一个实施方案涉及一种处理或抑制表面上生物膜形成的方法。这涉及提供具有或易感生物膜形成的表面，该生物膜由微生物产生，因此生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予表面，因此处理或抑制了表面上生物膜形成。
本发明通过人工诱导细菌经过生物膜分散的生理学处理，来解决″生物膜问题″。诱导分散的能力将允许直接控制生物膜，并将改善已有的生物杀灭剂、局部抗生素、去污剂等处理。人工分散将有益的情况的实例包括改善的接触透镜和牙齿的清洁、在家中、在工业中和在医疗社区中提高的防腐剂活性和现有的抗生素治疗例如感染铜绿假单胞菌(Pseudomonas aeruginosa)的烧伤患者的抗生素治疗增强的杀灭活性。
附图简述
图1A-B是用抗生素和/或分散诱导剂处理生物膜的图示代表。如图1A所示，在处理之后，仅在生物膜表面上的细胞被抗生素杀灭。图1B是与抗生素处理一起诱导分散的生物膜的图示代表。分散的细胞在处理期间被完全杀灭。
图2A-C描绘添加氯仿提取的用过(spent)培养基(CSM)对铜绿假单胞菌(Pseudomonas aeruginosa)的成熟生物膜的影响，该用过培养基包含诱导分散的化合物。图2A显示在流动池中载玻片上按连续培养生长的生物膜。图2B显示在添加分散诱导剂之后5分钟生物膜的相同区域。图2C显示在用分散诱导剂初始处理30分钟之后生物膜的完全解聚。
图3A是生物膜生命周期的图示代表。1，悬浮细菌转移(主动和被动地)至基底膜。2，细胞表面分子与基底膜相互作用，导致可逆的表面附着。3，细菌细胞中的表型改变导致细胞表面修饰和细胞外聚合物质的产生，这使细胞不可逆地粘结至表面。4，随着生物膜成熟的发生，连续发生生理学变化，并且在代谢、细胞-细胞信号和形态学方面发生改变。5，随着生物膜分离的发生，细胞释放降解酶消化基质聚合物材料，并改变表面附属物。在图3B的底部显微照片系列按顺序显示铜绿假单胞菌(P.aeruginosa)生物膜发育第5期的相衬显微照片，该铜绿假单胞菌(P.aeruginosa)在流动池内按连续培养生长并通过显微镜成像。(Sauer等，″铜绿假单胞菌(Pseudomonas aeruginosa)在作为生物膜发育期间显示多个表型″，J.Bacteriol.184：1140-1154(2002)，该文献通过引用而整体结合到本文中)。
图4A-B是由流动的停止诱导的生物膜20分散的相衬显微照片。图4A显示在流动条件下的早期生物膜发育，而图4B是在流动停止72小时之后同样的位置。
图5是显示氯仿提取对用过培养基分散活性影响的图。生物膜在生物膜管状反应器内的EPRI培养基中以连续培养方式培养6天(Sauer等，″铜绿假单胞菌(Pseudomonas aeruginosa)在作为生物膜发育期间显示多个表型″，J.Bacteriol.184：1140-1154(2002)，该文献通过引用而整体结合到本文中)，并用用过培养基(对照)和氯仿提取的用过培养基(CSM)处理。以在培养管末端收集的培养流出物的光密度，测定细胞分散。误差线代表3次重复实验的标准差。
图6A显示按证明是自然分散响应的连续培养生长的铜绿假单胞菌(P.aeruginosa)生物膜的微集落。在生物膜发育的分散期期间，细菌开始在细胞簇内能动并通过微集落壁中的裂口流出大量的液体。各显微照片显示其内部已经按该方式排空的微集落。箭头表示空隙的位置。放大1000倍摄取图像；柱表示10μm。图6B是透射光的图像，图6C是显示尺寸依赖于分散响应的荧光图像。具有大于40μm直径×10μm厚度尺寸的按连续培养生长的生物膜微集落显示分散(左3)。在该最小尺寸下的微集落仍然为″实心″(右2显微照片)。荧光指示细胞的存在(在染色体上的lacZ报道基因)。所有的图像均为放大500倍的同样的相对尺寸；柱表示40μm。箭头表示微集落内的空隙区域。
图7A-D显示用用过培养基、CSM和顺-2-癸烯酸处理铜绿假单胞菌(P.aeruginosa)成熟生物膜。如图7A中所示，在30min时，使在聚硅氧烷管中生长的生物膜暴露至用过培养基或新鲜培养基。连续收集流出物中的细菌100min，并通过OD600测定细胞密度。如图7B所示，使生物膜在聚硅氧烷管中按连续培养生长4天，并转换至新鲜培养基生长1hr，或转换至CSM生长1hr。对照管的挤出内容物显示完整的生物膜。CSM处理的生物膜的挤出内容物显示分散。如图7C中所示，显微照片显示将CSM添加至在显微镜安装的流动池中按连续培养生长的成熟生物膜。微集落解聚显示在7min开始。在暴露30min之后，微集落已经完全解聚。分散的细胞是主动能动的(在静态图像中不可见)，表明与在完整微集落(在CSM添加前)中的细胞相比表型发生变化。如图7D所示，将10μM顺-2-癸烯酸(顺-DA)添加至在显微镜安装的流动池中按连续培养生长的成熟生物膜中。微集落解聚显示在11min开始。完全的微集落解聚显示在30min暴露时间内。用载液处理的对照生物膜处理长达1hr不受影响。
图8A-B显示在CSM连续存在下的生物膜发育，该CSM用改良的EPRI稀释至用过培养基的浓度。在CSM存在下生长的生物膜的平均厚度(图8A)和表面积(图8B)显著小于未处理的生物膜。灰色柱表示用CSM处理的生物膜。黑色柱表示在分散诱导剂存在下生长的生物膜。误差线代表20个随机选择的微集落的一个标准差。
图9显示使用微量滴定板分散生物测定法，不同细菌生物膜通过铜绿假单胞菌(P.aeruginosa)CSM的分散。Y轴表示在3次重复实验中，在用CSM或含载体对照(-)的无菌培养基处理1hr之后，释放至16个平行测定孔的批量液体内的细胞数。阴影线表示在载体对照样品中分散的水平。在通过Student T检验测定所示的P值下，CSM样品与对照之间的所有差异均在统计学上有显著性。
图10A-C显示微量滴定板分散生物测定。图10A显示从含生物膜的微量滴定板孔释放的细胞的光密度。白色柱表示用EPRI单独处理的对照样品。灰色柱表示用CSM处理的样品。黑色柱表示用CSM的C-18反相HPLC流份处理的生物膜，该HPLC用2％-75％的乙腈梯度洗脱。结果是16个平行测定孔的平均值，误差线表示一个标准差。CSM和22分钟HPLC样品的Student T检验结果显示P＜0.001。图10B显示各种浓度的顺-2-癸烯酸与用过培养基比较的微量滴定板生物膜分散生物测定。从含生物膜的微量滴定板孔释放的细胞的光密度。阴性对照孔包含用10％乙醇/EPRI处理的铜绿假单胞菌(P.aeruginosa)。灰色柱表示用用过培养基处理的生物膜。黑色柱表示用增加顺-2-癸烯酸浓度的10％乙醇溶液处理的生物膜。结果是16个平行测定孔的平均值，误差线表示一个标准差。与对照比较，所有顺-2-癸烯酸样品的Student T检验显示P＜0.001。图10C显示顺-2-癸烯酸的结构。
图11显示使用微量滴定板分散生物测定法，不同细菌生物膜通过顺-2-癸烯酸的分散。Y轴表示在用含0.01μM顺-2-癸烯酸(CDA)或载体对照(-)的培养基+10％乙醇处理1小时后，在3次重复的实验中，释放至16个平行测定孔的批量液体内的细胞数量。阴影线表示在载体对照样品中分散的水平。在通过Student T检验测定所示的P值下，在顺-2-癸烯酸处理的样品和对照之间的所有差异均具有统计学显著性。
图12A-C显示铜绿假单胞菌(P.aeruginosa)CSM和顺-2-癸烯酸的光谱分析。图12A显示171M/Z分子的产物离子质量峰，该分子在活性HPLC CSM流份中检测到，并用于合成顺-2-癸烯酸。Y轴表示强度；X轴表示阳离子模式的M/Z。CSM样品与合成顺-2-癸烯酸的峰匹配。注意在质谱中，峰强度不是浓度的直接指示。图12B显示铜绿假单胞菌(P.aeruginosa)CSM和顺-2-癸烯酸的GC-MS图谱。在15.9分钟的CSM样品峰表示溶剂载体。Y轴表示强度；X轴以分钟表示时间。图12C显示铜绿假单胞菌(P.aeruginosa)CSM和顺-2-癸烯酸的FT-IR图谱。Y轴表示吸收度；X轴表示厘米的倒数。
图13显示将10μM顺-2-癸烯酸(顺-DA)添加至成熟生物膜中，该生物膜在显微镜安装的流动池内按连续培养生长。微集落解聚显示在11分钟开始。在15分钟暴露时间内显示完全的微集落解聚。用载液处理的对照生物膜不受处理长达1小时的影响。
发明详述
本发明的一个方面涉及一种组合物。该组合物包括一种或多种分散诱导剂，该分散诱导剂包含：
Figure G2008800246911D00121
其中
Figure G2008800246911D00131
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。该组合物还包含选自以下的一种或多种添加剂组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。将所述组合物配制成使其当与由微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，所述分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应，以将该生物膜分散。在达到该结果中，本发明的分散诱导剂优选可以直接作用于基质。或者，分散诱导剂可以作用于微生物，这又用于破坏基质。该效果也可涉及不依赖于对基质直接作用。典型地，生物膜诱导剂对基质将没有直接作用或以对基质无直接作用的浓度存在是显然的。在另一方面，有效浓度的范围提出微生物内的生化反应机制，其中分散诱导剂模拟细胞间通讯组合物。该组合物用于通过细菌诱导分散响应，这又对细菌从生物膜释放起作用。此外，该组合物能够作用于不在生物膜内的细菌(悬浮细菌)，包括具有防止生物膜形成的生理学反应的这些细菌。组合物的另外组分可涉及从表面或基体破坏或除去基质。例如，组合物可包含适合于从牙齿摩擦除去噬菌斑的洁齿剂。
以上诱导剂的R基团可选自：
Figure G2008800246911D00141
或者，R可以是高丝氨酸内酯或呋喃酮基团。所述组合物也包括添加剂组分，例如以下组分中的一种或多种：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物或可咀嚼产物。
本发明的分散诱导剂期望包含7-10个碳原子。优选该诱导剂是羧酸(例如单不饱和脂肪酸)。更优选分散诱导剂包含：CH3-(CH2)n-CH＝CHCOOH该分散诱导剂的合适的非盐形式分别是以下的顺式和反式异构体：
Figure G2008800246911D00151
其中，优选顺式异构体。
其它合适的链烷酸包括己酸、庚酸、辛酸、壬酸、癸酸、十一烷酸、十二烷酸、十三烷酸、十四烷酸、十五烷酸、十六烷酸、十七烷酸、十八烷酸和十九烷酸。
有用的链烯酸包括2-己烯酸、2-庚烯酸、2-辛烯酸、2-壬烯酸、2-十一碳烯酸、2-十二碳烯酸、2-十三碳烯酸、2-十四碳烯酸、2-十五碳烯酸、2-十六碳烯酸、2-十七碳烯酸、2-十八碳烯酸和2-十九碳烯酸。这些可以是顺式或反式异构体。
如下，本发明的组合物可以在许多的pH范围配制，以治疗不同类型的细菌：1.5-4.5用于嗜酸性细菌；4.5-8.0用于耐酸菌；6.8-7.4用于嗜基本上中性pH的细菌；和8.0-9.8用于耐碱菌。对于酸逆流受试者，基本上中性的pH尤其理想。分散诱导剂的浓度可以是0.01μM-30mM。
所述组合物可以完全或基本上(即小于10％重量)不含乙醇和/或不含甲醛。
本发明也包括用所述组合物涂布的表面(或基体)。
本发明的另一个方面涉及一种治疗或预防受试者中由生物膜介导的病症的方法。该方法包括提供具有或易感由生物膜介导的病症的受试者，该生物膜由微生物产生，因此该生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予受试者，该分散诱导剂包含：
Figure G2008800246911D00152
其中
Figure G2008800246911D00153
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。结果，治疗或预防了在受试者中由生物膜介导的病症。将生物膜分散的方法还可包括与给予分散诱导剂联合，给予生物膜抗微生物处理。该处理可以是给予生物杀灭剂(例如过氧化氢)、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物、可咀嚼产物、超声波处理、放射处理、热处理和/或机械处理。
本发明的又一个方面涉及一种处理或抑制表面上生物膜形成的方法。该方法包括提供具有或易感生物膜形成的表面，该生物膜由微生物产生，其中该生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予表面，该分散诱导剂包含：
Figure G2008800246911D00161
其中
Figure G2008800246911D00162
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。结果，处理或抑制了表面上生物膜的形成。
在一个实施方案中，待处理的表面包括留置医疗装置，例如导管、呼吸器和通风器。另外，表面可以在植入的医疗装置中，该植入的医疗装置包括支架、人工瓣膜、关节、钉、骨植入物、缝合线、U形钉、起搏器和其它临时性或永久性装置。本发明的分散诱导剂也可以包含在外科用胶中。在另一个实施方案中，待处理的表面包括排泄装置、桶状物、厨房用具、工作台面、淋浴帘、薄浆、盥洗室、工业食品和饮料生产设施、地板和食品加工设备。在还一个实施方案中，待处理的表面是热交换器表面或过滤器表面。因此，处理提供了降低热交换器或过滤器生物结垢程度的手段。在最终的实施方案中，待处理的表面是海上构筑物，包括船、桥墩、石油平台、水摄取口、筛网和观察口。表面或者可以与水处理和/或分配系统(例如饮用水处理和/或分配系统、池和矿泉水处理系统、制造操作中的水处理和/或分配系统和牙科水处理和/或分配系统)相联系。表面也可以与石油钻探、贮藏、分离、精制和/或分配系统(例如石油分离列车、石油容器、石油分配管和石油钻探设备)相联系。分散诱导剂也可以包括在一些制剂中，这些制剂针对减少或消除在多孔介质，例如负载油和气的地质构造的多孔介质中生物膜沉积或生物结垢。所述处理可通过将涂层例如漆涂覆至表面来完成。
在表面上抑制生物膜形成的方法还可包括与给予分散诱导剂联合给予表面抗微生物处理。可以给予以下的处理：生物杀灭剂、表面活性剂、抗生素、防腐剂、消毒剂、药物、去污剂、螯合剂、毒力因子抑制剂、超声波处理、放射处理、热处理和机械处理。在一个实施方案中，分散诱导剂和抗微生物处理同时给予。在另一个实施方案中，分散诱导剂和抗微生物处理分别给予。
为了抑制在表面上形成生物膜，可以将分散诱导剂浸渍在表面内。或者，分散诱导剂可以在涂布在表面上的共聚物或凝胶中。
本发明也涉及治疗烧伤受试者的方法。该方法包括在对治疗受试者的烧伤有效的条件下，给予本发明的分散诱导剂。本发明的具体应用提供用于烧伤患者的局部敷料，该局部敷料包含诱导分散的分子或其天然或合成类似物，以防止有传染性的生物膜发育，或分散已有有传染性的生物膜的细胞。
本发明还涉及在受试者中治疗和/或预防牙斑、龋齿、齿龈疾病、牙周病和口腔感染的方法。该方法包括用本发明的分散诱导剂处理受试者的口腔。可以用含分散诱导剂的洁齿剂、漱口剂、牙线、胶、条状物、牙膏、牙刷，和含分散诱导剂的其它制剂来进行处理。所述组合物也可包含通常添加至牙用组合物的在牙科领域中已知的其它化合物。例如，分散诱导剂组合物也可包括氟化物、脱敏剂、防牙垢剂、抗菌剂、再矿化剂、增白剂和抗龋剂。
分散诱导剂存在的量将根据包含分散诱导剂的牙用组合物而改变。已经发现分散诱导剂在宽的浓度范围内具有抗口腔细菌的活性。例如，分散诱导剂可以0.1nM-10mM的量存在。然而，可使用更低和更高的浓度，这取决于牙用组合物、存在于分散诱导剂组合物中的其它组分和本领域中的技术人员所认识到的各种其它因素。分散诱导剂的已知性质，例如其脂肪酸特性及其疏水性将协助熟练的技术人员决定应该使用多少分散诱导剂，决定化合物将如何与其它组分化学相互作用，并提供关于化合物的其它有用的信息。
本发明中考虑具体的牙科应用和牙用组合物。在这点上，本发明涉及包含分散诱导剂组合物的牙刷。如在本领域中所熟知的，牙刷包含许多刷毛和刷毛固定在其上的固体载体，其中固体载体包括具有许多接受刷毛的簇毛孔的刷头。在本领域中熟知基本牙刷的变化和改进。见例如美国专利第7,251,849号，该专利通过引用而整体结合到本文中。
本发明的分散诱导剂具有如上所述的化学式。上面也阐述了可包括于分散诱导剂组合物中的另外组分。可通过在本领域中已知的方法，将分散诱导剂组合物掺入牙刷的各种部件中。例如，分散诱导剂组合物可包含于牙刷的簇毛孔中。对于组合物如何可以包含在牙刷的簇毛孔内的实例，见美国专利第5,141,290号，该专利通过引用而整体结合到本文中。或者，分散诱导剂组合物可涂布或包埋在牙刷的刷毛内。
牙刷的其它部件也可涂布或包埋有分散诱导剂组合物，包括补充刷毛和设计与口腔接触的牙刷的任何部件。例如，牙刷通常包含橡胶桨、舌清洁器或用于与牙齿、舌、牙龈或口腔其它区域接触目的的从头部延伸的其它部件。这些部件可包埋有分散诱导剂组合物，和任选表面活性剂、生物杀灭剂和/或上述的其它添加剂。
为了有助于控制分散诱导剂从牙刷释放，分散诱导剂组合物可包含与分散诱导剂相互作用以有助于控制释放的试剂。该试剂可按取决于预定用途而加速或延长释放的方式，与分散诱导剂相互作用。控制释放的水平也可以取决于分散诱导剂如何容易或困难地粘附至其施加至的牙刷部分。在优选的实施方案中，分散诱导剂在反复的刷牙过程中从牙刷缓慢释放。本领域的技术人员熟知能够保证活性成分缓慢释放的试剂。
也可通过将分散诱导剂包封在允许控制释放的囊化系统，来实现控制释放。在该实施方案中，分散诱导剂组合物优选为将分散诱导剂包封的许多小的微球形式。该微球可以具有可溶性材料的外部涂层，其确保分散诱导剂在反复刷的时间内能够缓慢释放。合适的微球包括在美国专利第5,061,106号中公开的那些，该专利通过引用而整体结合到本文中。
本发明也涉及牙膏组合物，该组合物包含：(a)氟化物和/或再矿化剂；(b)口腔可接受的溶媒；和(c)分散诱导剂组合物。本发明的分散诱导剂具有如上所述的化学式。上面也阐述了可包括于分散诱导剂组合物中的另外组分。通常，牙膏也包含月桂基硫酸钠或其它的硫酸盐。
其各种形式的氟化物是牙膏中的常用活性成分，用于防止空洞并促进牙釉质和骨的形成。任何氟化物源，例如氟化物盐可用于本发明的牙膏中。优选，氟化物是氟化钠(NaF)或单氟磷酸钠(Na2PO3F)。典型地，存在于牙膏中的氟化物的量的范围为每百万氟化物离子100-5000份，优选每百万1000-1100份。
在某些情况中，优选用再矿化剂取代或补充氟化物。在牙科用法的上下文中，再矿化一般指治疗牙齿以便预防龋齿，或减少其发生的机会，和另外增强牙齿以便它们可以恢复到其最初的健康状态。虽然可以认为氟化物是再矿化剂，但其它试剂常常代替氟化物或补充氟化物，以提供牙膏更强的清洁或再矿化性质。常用再矿化剂是钙盐，例如磷酸钙、硫酸钙、无水硫酸钙、硫酸钙半水合物、硫酸钙二水合物、苹果酸钙、酒石酸钙、丙二酸钙和琥珀酸钙。羟磷灰石纳米晶体和锌化合物也已显示是有效的再矿化剂。
口腔可接受的溶媒可以是可以用于使氟化物和/或再矿化剂和分散诱导剂释放至患者牙齿的本领域中已知的任何溶媒。口腔可接受的溶媒也可以是甘油、丙二醇、聚乙二醇、甘油三酸酯、甘油二酸酯、矿物油、有机油、精油、植物脂肪油及其组合。通常这些溶媒与水或水基溶剂组合使用。
牙膏组合物可包含在本领域中熟知的牙膏的其它组分。例如，牙膏组合物可包含碳酸氢钠、酶、维生素、草药、钙化合物例如磷酸硅酸钙钠、着色剂和/或矫味剂。也可添加脱敏剂。如在本领域中已知的，脱敏剂可以通过治疗由脱矿质引起的过敏而降低牙齿的敏感性，或通过使神经脱敏而抑制过敏症状。该组合物也可包含抗菌剂或抗斑剂。优选抗菌剂包括在预防龈炎、牙周炎和其它口腔疾病的组合物中。合适的抗菌剂包括三氯生、氯化锌、氯己定、苄索氯铵(benzthonium chloride)和氯化十六烷基吡啶鎓。
本发明也涉及用于治疗和/或预防牙斑、齿龈疾病、牙周病和/或口腔感染的口腔组合物。该口腔组合物包含口腔可接受的溶媒和分散诱导剂组合物。本发明的分散诱导剂具有如上所述的化学式。上面也阐述了可包括于分散诱导剂组合物中的另外组分。
口腔组合物可以是本领域技术人员已知的口腔卫生领域中的各种组合物。例如，口腔组合物可以是漱口剂、呼吸喷雾剂(breathspray)、洁齿剂、牙粉、增白条状物或预防性糊剂。如本领域中所熟知的，漱口剂通常用于帮助除去在口腔或咽喉中的粘液和食物颗粒。漱口剂通常包含防腐剂和/或抗斑组分，以杀灭引起龋齿、龈炎和口臭的菌斑。它们也可以包含抗空洞组分例如氟化物，以防止牙齿腐蚀。合适的漱口剂组分可于美国专利第5,968,480号中发现，该专利通过引用而整体结合到本文中。
同样，相同或相似的防腐剂、抗斑组分和抗空洞组分可以用于呼吸喷雾剂、洁齿剂包括凝胶洁齿剂、牙粉、增白条状物和预防性糊剂中。在美国专利第7,297,327号中公开了合适的呼吸喷雾剂组合物；在美国专利第5,989,526号中公开了合适的牙粉组合物，例如用于牙齿漂白组合物中的那些；在美国专利第6,514,483号中公开了合适的增白条状物；在美国专利第5,939,051号中公开了合适的洁齿剂和预防性糊剂组合物，包括牙齿磨擦剂，所有这些专利均通过引用而整体结合到本文中。
口腔可接受的溶媒成分与上述那些相似。然而，口腔可接受的溶媒将根据口腔组合物的期望一致性和期望的最终产品而改变。例如，漱口剂是液体形式，所以应该使用液体载体，通常为具有高百分比的水的载体。在另一方面，凝胶洁齿剂应该是凝胶形式，和将利用胶凝剂或使最终产品能够为凝胶形式的其它载体。口腔可接受的溶媒应该具有允许分散诱导剂组合物释放，同时也提供具有期望一致性的最终产品的性质。
口腔组合物也可以为口香糖、口气清新(breath)条状物、锭剂或薄荷糖(breath mint)的形式。口香糖通常是水不溶相或胶基质和甜味剂、矫味剂和/或食用色素的水溶相的组合。其它组分也可添加至口香糖，包括口气清新添加剂例如锌盐和磷酸盐、牙齿-增白添加剂例如二氧化硅和减少噬菌斑以缓解牙斑的添加剂。合适的口香糖组合物可于美国专利第6,416,744号和6,592,849号中发现，这两个专利均通过引用而整体结合到本文中。
口气清新条状物类似于口香糖，不同之处在于条状物设计在口中溶解，通常通过舌吸收。该条状物可以释放使口清新的生物活性成分以及功能性生物活性成分，例如维生素、矿物质、补充剂、药物和疫苗。
锭剂和薄荷糖通常为在矫味基质中含治疗剂的盘状固体。基质可以是硬冰糖、甘油胶或糖与足量粘质物的组合，以给予组合物要求的形式。分散诱导剂可代表治疗剂，或除本领域中已知的治疗剂外它可加入。在美国专利第7,025,950号中公开了合适的锭剂和薄荷糖组合物，该专利通过引用而整体结合到本文中。
口腔组合物也可以是置入口腔的牙用装置的清洁制剂形式。将牙用装置例如假牙、牙科橡皮障和某些类型的牙矫正架置入口腔一段时间，然后周期性地取出清洁。用于清洁牙用装置的清洁组合物应该以其清洁装置的惯用方式起作用，但也可包含治疗剂，当牙用装置与口腔接触时，该治疗剂可以有助于治疗或预防牙斑、齿龈疾病、牙周病和口腔感染。清洁组合物例如泡腾清洁剂用本领域中已知的含氯化合物的碱性混合物等制备。在美国专利第3,936,385号中公开了牙用装置的合适清洁组合物，该专利通过引用而整体结合到本文中。可以以使其能够在接触后涂覆牙用装置的方式，将分散诱导剂添加至清洁组合物。在将牙用装置引入口腔之后，分散诱导剂可以以治疗有效的方式与牙齿和口腔的其它元件相互作用，即以预防牙斑、齿龈疾病、牙周病和/或口腔感染。
本发明也涉及包含牙用物品和分散诱导剂的口腔使用物品。分散诱导剂具有以上所述化学式，并涂布、包封在或浸渍在牙用物品内。上面也阐述了可包括于分散诱导剂组合物中的另外组分。
在本领域中已知的各种牙用物品可用于本发明的该实施方案中。在一个实施方案中，牙用物品是牙线。在本领域中已知的任何纤维均可用于牙线中。合适的纤维包括聚酰胺(例如尼龙)、聚酯、聚丙烯、聚四氟乙烯、纤维素和棉花。尼龙和聚四氟乙烯纤维是用于牙线中的最常见纤维并代表优选的纤维。在美国专利第6,270,890号和6,289,904号中公开了合适的牙线，这两个专利均通过引用而整体结合到本文中。可使分散诱导剂组合物浸渍在纤维内，涂布在纤维上，或另外掺入牙线内。
牙线可用蜡或其它疏水性物质涂布或浸渍，以便易于在线处理期间使用。合适的蜡包括微晶蜡、蜂蜡、石蜡、巴西棕榈蜡和聚乙烯蜡。可将分散诱导剂组合物涂布在牙线上，作为蜡层的一部分，作为与蜡层连接的第二层或另一层，或如上所述施加至纤维。
牙用物品可以是用分散诱导剂组合物浸渍或涂布的牙签。牙签可由天然产物例如木材或人造组分包括各种塑料制备。在美国专利第7,264,005号中公开了合适的牙签，该专利通过引用而整体结合到本文中。
牙用物品也可以是牙用器具例如吸牙器、牙合堤、牙障、舌稳定器、压舌器或牙科医生或牙科助理医师可用于患者口中的牙用设备的任何其它部件。牙用器具的讨论可于美国专利第4,865,545号和5,152,686号中发现，这两个专利均通过引用结合到本文中。牙用器具与患者口腔接触的部分可用分散诱导剂组合物涂布。
牙用物品也可以是牙构造物，例如放置在牙齿上的镶盖、冠、嵌体、高嵌体或齿桥。牙构造物通常由金属合金、瓷、陶瓷、汞合金、丙烯酸酯聚合物或这些材料的组合制成。在美国专利第7,229,286号公开了合适的牙构造物，该专利通过引用而整体结合到本文中。分散诱导剂组合物可包埋在用于制备牙构造物的组合物中。或者，可在其制备之后将分散诱导剂组合物涂布在牙构造物上。
本发明也涉及含水组合物，该含水组合物施用至使用牙用物品的口腔，该含水组合物包含水和分散诱导剂组合物。各种牙用物品附接至或设计与水管线(water line)一起使用，以便水可以通过牙用物品分配，然后按规定路线从牙用物品至受试者的口腔。合适的牙用物品包括牙水管线、牙齿喷水器(dental water picks)等。
虽然自来水或纯化水可用于这些类型的牙用装置，但水源也可用添加剂补充，以便当与牙用物品一起使用时，水递送添加剂至受试者的口腔。在该情况下，补充至水中的添加剂是分散诱导剂组合物。
牙水管线和牙齿喷水器在本领域中已知，且经常被牙科医生和牙科助理医师使用。不同类型的牙水管线及其不同应用的讨论可于美国专利第5,785,523号中发现，该专利通过引用而整体结合到本文中。在美国专利第4,257,433号中公开了合适的喷水器，该专利通过引用而整体结合到本文中。
本发明也涉及将接触透镜清洁和/或消毒的方法。该方法包括用清洁和/或消毒溶液处理接触透镜，该清洁和/或消毒溶液含本发明的分散诱导剂。当贮藏在溶液中或当在体内使用时，接触透镜可以该方式处理。或者，分散诱导剂可以用于滴眼剂。
本发明还涉及治疗和/或预防受试者皮肤上的痤疮或其它生物膜相关的皮肤感染的方法。该方法包括在对治疗和/或预防痤疮或生物膜相关的皮肤感染有效的条件下，用本发明的分散诱导剂处理受试者的皮肤。分散诱导剂可存在于乳膏剂、软膏剂、搽剂、油膏剂、修面洗剂或须后润肤膏中。其也可存在于散剂、化妆品、乳膏剂、软膏剂、液体、肥皂、凝胶、化妆涂布器和/或固体、预定与皮肤接触或接近的织造或非织造材料。
本发明也涉及在受试者中治疗和/或预防慢性生物膜相关疾病的方法。该方法包括在对治疗和/或预防慢性生物膜相关疾病有效的条件下，将本发明的分散诱导剂给予受试者。治疗和/或预防的慢性生物膜相关疾病包括但不限于中耳感染、骨髓炎、前列腺炎、结肠炎、阴道炎、尿道炎、动脉斑块、滑膜感染、沿组织筋膜的感染、呼吸道感染(例如与囊性纤维化患者的肺感染相关的感染、肺炎、胸膜炎、心包感染)、泌尿生殖道感染和胃或十二指肠溃疡感染。对于幽门螺旋杆菌(Helicobacter pylori)引起的胃或十二指肠溃疡，分散诱导剂将需要在低于5.5的pH下起作用。分散诱导剂可与抗微生物剂例如生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂或毒力因子抑制剂联合给予。在胃治疗的情况下，也可使用降低酸的疗法，例如抗酸剂、质子泵抑制剂、抗组胺药等。
本申请的另一个方面涉及一种溶液，该溶液包含分散诱导剂，该分散诱导剂包含：
Figure G2008800246911D00241
其中
Figure G2008800246911D00242
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸，其中所述诱导剂以小于0.5％重量的浓度存在，且其中所述溶液的pH大于5。
本发明的又一个方面涉及一种组合物，该组合物包含选自以下组分中一种或多种的组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。此外，该组合物包括分散诱导剂，该分散诱导剂包含：
Figure G2008800246911D00251
其中
Figure G2008800246911D00252
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸。将诱导剂配制成非盐形式。
本发明也涉及一种溶液，该溶液包括2-癸烯酸的顺式异构体，其中该溶液选自皮肤软膏剂、牙膏和漱口剂，且其中该溶液基本上不含2-癸烯酸的反式异构体。如本文所解释的，假如反式异构体浓度的降低(顺式异构体没有变化)不增加生物活性，则该溶液基本上不含反式异构体。更优选顺式与反式的摩尔比至少为2。
本申请的另一种形式涉及一种溶液，该溶液包含2-癸烯酸的顺式异构体，其中该溶液选自皮肤软膏剂、牙膏和漱口剂，且其中所述溶液不含反式异构体。
本申请的另一种形式是一种方法，该方法包括提供接触透镜和包含浓度小于0.5％重量的分散诱导剂的溶液，所述诱导剂包含：
Figure G2008800246911D00253
其中
Figure G2008800246911D00254
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。然后用所述溶液处理接触透镜。
本发明的又一种形式是一种方法，该方法包括提供有皮肤病的受试者和pH大于5的溶液，其中该溶液包含浓度小于0.5％重量的分散诱导剂，所述诱导剂包含：
Figure G2008800246911D00255
其中是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸、盐、酯或酰胺，其中酯或酰胺是羧酸的电子等排体或生物等排体。然后用该溶液治疗皮肤病。
本发明也涉及包含一种或多种分散诱导剂和一种或多种添加剂组分的组合物。这些添加剂组分选自生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。将所述组合物配制成使其当与微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，所述分散诱导剂选择性地作用于微生物并具有合适的生物反应，而不需要直接作用来将基质破坏。
本发明的另一个方面涉及治疗或预防受试者中由生物膜介导的病症的方法，该方法包括提供受试者，该受试者具有或易感生物膜介导的病症，该生物膜由微生物产生，因此该生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予受试者，因此治疗或预防了受试者中由生物膜介导的病症。
本申请的又一个实施方案涉及处理或抑制表面上生物膜形成的方法。这包括提供具有或易感生物膜形成的表面，该生物膜由微生物产生，因此该生物膜在表面上包含基质和微生物。在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予表面，因此处理或抑制了表面上生物膜的形成。
实施例
提供以下实施例，以举例说明本发明的实施方案，但决无意限制其范围。实施例1-菌株和培养基
用于该研究的微生物包括得自B.H.Holloway的铜绿假单胞菌(Pseudomonas aeruginosa)PAOl、大肠杆菌(Escherichia coli)(ATCC 10798)、奇异变形杆菌(Proteus mirabilis)(ATCC 25933)、肺炎克雷伯氏菌(Klebsiella pneumoniae)(ATCC 10273)、金黄色葡萄球菌(Staphylococcus aureus)(ATCC 12602)、化脓性链球菌(Streptococcuspyogenes)(ATCC 19615)、枯草芽孢杆菌(Bacillus subtilis)(ATCC 6633)和白色念珠菌(Candida albicans)(ATCC 20260)和经空气传播污染在R2A板上收集的混合的未定义培养物。除非另外指定，否则所有的实验在改良的EPRI培养基中进行，该EPRI培养基包含0.005％硝酸铵、0.00019％KH2PO4、0.00063％K2HPO4(pH 7.0)和0.001％Hutner盐(Cohen-Bazire等，J.Cell.Comp.Physiol.49：35(1957)，该文献通过引用而整体结合到本文中)，其补充0.2％葡萄糖。白色念珠菌(C.albicans)生长在补充0.2％葡萄糖和0.1％蛋白胨的改良的EPRI培养基中。肺炎克雷伯氏菌(K.pneumoniae)、奇异变形杆菌(P.mirabilis)、金黄色葡萄球菌(S.aureus)和枯草芽孢杆菌(B.subtilis)生长在补充0.1％蛋白胨的改良的EPRI培养基中。化脓性链球菌(S.pyogenes)生长在10％脑心浸液肉汤中。实施例2-铜绿假单胞菌(P.aeruginosa)用过培养基的制备
为了制备无细胞的用过培养基，将于30℃下在改良的EPRI培养基中生长的铜绿假单胞菌(P.aeruginosa)PAO1的6mL过夜培养物，接种至4升的改良EPRI培养基中，并在连续搅拌下，室温温育10天。通过在4℃下，在13,000×g下离心15分钟(Sorvall RC 5B PlusCentrifuge，GSA Rotor；Thermo Electron Co.，Ashville，NC)，使细菌细胞沉淀。将上清液取出，并通过0.45μm微孔型HA过滤器(Millipore.Co.，Billerica，MA)，接着通过0.2μm，Acrodisc 32mm注射器过滤器(PALLCo.，East Hills，NY)在真空下过滤。用过培养基贮藏在4℃下。实施例3-CSM的制备
通过将80mL氯仿添加至分液漏斗中的250mL过滤的用过培养基中，来提取用过培养基的有机组分。在1hr的分离时间之后，将氯仿部分取出。使用Rotavapor R-3000旋转蒸发器(Büchi Laboratories，Flawil，Switzerland)在40℃下蒸发氯仿，并将剩余的有机物质再悬浮于6mL过滤的纳米纯水中，并使用Speed-Vac蒸发器系统(SavantInstruments，Inc.，Hicksville，NY)蒸发至干，或冻干。然后将这些样品再悬浮于培养基或纯化水中。最终产物称为氯仿提取的用过培养基(CSM)。除非另外指明，CSM均以比在用过培养基中发现的高125倍的最终氯仿提取的有机碳浓度，用于实验中。实施例4-CSM的HPLC分级分离
使用C18Microsorb-mv反相柱(Varian Inc.)，尺寸为250×4.6mm，通过高效液相色谱(HPLC)(Varian Prostar model 320，Varian Inc.，Palo Alto，CA)，将CSM分离。柱装载100μL的CSM，并用乙腈/水梯度(2-75％)，以1mL×min-1的流速洗脱29分钟。从2分钟开始，每分钟收集样品。合并HPLC流份，并在Speed Vac浓缩器(SavantInstruments，Inc.，Hicksville，NY)中浓缩，然后再悬浮于0.5mL改良的EPRI培养基或纯化水中。发现用70％乙腈/30％水，将活性HPLC流份从柱中洗脱出来。通过微量滴定板分散生物测定法，测定每次HPLC分离的活性流份。实施例5-微量滴定板分散生物测定
微量滴定板分散生物测定用于测试各种制剂的外源性诱导生物膜分散的能力。使用半分批培养法，使生物膜生长在微量滴定板孔的内表面上，其中将各孔内的培养基周期性地更换，以减少天然分散诱导因素的积聚。将以该方式生长的生物膜用分散诱导剂或无菌培养基处理，以将细胞释放至批量液体中，并通过测量光密度来评估分散的细胞数。简而言之，将无菌聚苯乙烯96孔板用丙酮蚀刻10秒，以形成用于微生物细胞附着的粗糙表面。在干燥24小时之后，板用150μL/孔的过夜培养物接种，该过夜培养物含有试验生物体，先用生长培养基稀释1∶20，然后在200rpm下，在30℃下振摇温育。将孔中的培养基每24小时更换，持续5天，并在第6天和第7天每12小时更换。然后在7小时后更换培养基。通过以下方法来测试分散诱导：添加150μL含分散诱导剂的生长培养基，在30℃下持续1hr，或添加无菌培养基作为对照。然后，通过移液管将含分散细胞的培养基转移至未蚀刻的微量滴定板中，并测定光密度(OD570)(ELx808吸收度微量板阅读器；BioTek Instruments，Inc.，Winooski，VT)。处理组由各种浓度的用过培养基、CSM、顺-2-癸烯酸、反-癸烯酸、癸酸和DSF组成。乙醇(10％)用作脂肪酸诱导剂样品的载体，并确定它对分散没有影响。使用该方法的结果在不同处理组的比较中很有意义，并确定分散活性是否具有统计学显著性。注意：微量滴定板分散生物测定不适合于确定诱导分散响应的绝对量，因为在半分批系统中，对照和试验样品对自然分散敏感，测量对该自然分散的外源性诱导活性。所有的效力研究均使用生物膜管状反应器或流动池连续培养系统来进行，且均基于总细胞计数和活细胞计数。实施例6-生物膜管状反应器中的分散生物测定
使铜绿假单胞菌(P.aeruginosa)PAO1生物膜培养物生长在如前面Sauer等所述的管状反应器中(K.Sauer等，J.Bacteriol.184：1140(2002)，该文献通过引用而整体结合到本文中)。使用8根聚硅氧烷反应器管(81.5cm长×14mm ID)，该反应器管经另外的聚硅氧烷管连接至8辊头蠕动泵和培养基贮器，来装配连续的单程管状反应器系统。培养基通过管泵送至关闭的流出培养基贮器。在接种前，通过高压灭菌使装配的系统灭菌。通过注射器注射，穿过从各反应器管开始上游1cm的隔膜，使聚硅氧烷管接种铜绿假单胞菌(P.aeruginosa)的2mL过夜培养物(含约1×108CFU mL-1)。允许细菌细胞附着(静止温育)至管，持续1小时，然后，以10.8mL hr-1的洗脱速率开始流动。在铜绿假单胞菌(P.aeruginosa)PAO1生物膜培养96小时之后，进行处理。该处理在连续和静止的条件下进行。
在连续处理下(图17A)，流入的培养基从实验系(test line)中的新鲜培养基变成用过培养基，该用过培养基用2％葡萄糖改良，调节至中性并在添加前充气过夜。对照系(controlline)转换成新的系，该新的系含新鲜的改良EPRI培养基。从时间＝0min开始，在1分钟的时间间隔，收集样品，并测定光密度。在时间＝30min时添加用过培养基。将样品收集在冰上的试管中，接着用Tissue Tearor 985370型(Biospec Products，Inc.)在5000rpm下匀化30秒，以保证细胞的分离。通过用Ultrospec 3000分光光度计(Amersham Pharmacia Biotech，Inc.)，在600nm下测定光密度，来测定细胞密度。
在静止处理的条件下，通过注射器注射，穿过从管状反应器开始上游2cm的接种口，将分散诱导剂加入，反应器体积用含诱导剂的培养基置换。直接添加用过培养基。在改良的EPRI中制备CSM或合成的分散诱导剂(例如顺-2-癸烯酸)并加入。在非流动条件下暴露1小时之后，将各聚硅氧烷管状反应器的81.5cm长度切掉，液体部分(包含释放的生物膜细胞)收集在冰上试管内，并通过用金属棒在实验室台上使管滚动以挤出保留在管腔内的细胞，来收集生物膜部分(K.Sauer等，J.Bacteriol.184：1140(2002)，该文献通过引用而整体结合到本文中)。将样品收集在冰上，并如上所述进行匀化。细胞数通过以下方法来测定：通过在标准板计数琼脂培养基(Difco，Detroit，MI)上的平板涂布培养法；或通过在OD600的光密度，该方法通过校准至通过总细胞计数用显微镜测定的细胞数的标准曲线，来调节细胞数。分散效力使用光密度或生存力测量值来计算：
Figure G2008800246911D00301
实施例7-显微镜分析
装配连续培养单程流动池，以观察附着至玻璃基底膜的生物膜的生长和发育。流动池由铝构成，包含用玻璃盖玻片盖住的室1.0mm×1.4cm×4.0cm。使用Masterflex 8辊头蠕动泵，以0.13mL/分钟的流速，使无菌改良的EPRI培养基从10升的容器，通过聚硅氧烷管泵送到流动池。流过室的是雷诺数为0.17的层流，流体停留时间是4.3分钟。离开流动池的培养基经聚硅氧烷管排放至流出物贮器。整个系统对外部环境关闭，但通过安装至各容器的0.2μm孔径可透气的过滤器来保持与大气压平衡。在流动条件下，穿过从流动池开始上游4厘米的隔膜，以3.0mL块剂量，接种对数期铜绿假单胞菌(P.aeruginosa)(约108CFU mL-1)。使用Olympus BX60显微镜和放大100倍的A100PL物镜或放大50倍的ULWDMSPlan长焦点距离的Olymus物镜，通过透射光或表面UV光照，观察附着于玻璃盖玻片内表面的细胞。使用Magnafire冷却型3芯片电荷耦合器件(CCD)照相机(Optronics Inc.，Galena，CA)捕获所有的图像，并存储为各数字化文件，用于以后检索和分析在流动池中生长最长达12天的铜绿假单胞菌(P.aeruginosa)。申请人以前的工作已经显示在连续培养7-9天之后铜绿假单胞菌(P.aeruginosa)发育为稳定状态的生物膜。稳定状态定义为因分离的生物膜细胞引起的流出物细胞计数(CFU)无变化；在稳定状态中，生物膜的生长与细胞通过分散或分离的损失达到平衡。在各实验过程中检查各细胞簇，并指定网格坐标，在试验过程中周期性地再检查。通过定位最接近随机选择的显微镜载物台坐标的簇，对随机的细胞簇进行尺寸测量。通过从簇的基底膜到顶点聚焦来测量各细胞簇，以确定其高度，使用载物台测微器在细胞簇的基部测量其宽度。细胞簇定义为包埋在附着于基底膜的表多糖基质中并缺乏运动性的细胞；通过观察在细胞簇内部的空间内自由游动的细菌，来测定细胞簇内的空隙面积。实施例8-生物膜发育的抑制
流动池用于在(上述的)玻璃基底膜的表面上培养细菌。使铜绿假单胞菌(P.aeruginosa)的生物膜在改良的EPRI培养基中，在CSM(稀释1∶125，以匹配在用过培养基中发现的氯仿提取的有机物质的浓度)的存在和不存在下，在99个小时的时间内，在室温下生长。在实验过程中，通过在各时间点使用50倍ULWD MSPlan物镜计数20个显微镜视野，来测定细菌在表面上的总细胞覆盖率和生物膜的平均厚度。使用图像分析软件ImagePro Plus，在72小时和99小时测定细胞总面积/cm2。通过测量生长72小时和99小时的20个随机细胞簇的平均最大高度，来测定厚度。使对照样品在没有添加CSM的改良EPRI培养基的存在下生长并测试。这些实验的结果显示，与在单独的ERPI培养基中生长的生物膜相比，当生物膜在CSM的存在下生长时，生长生物膜的表面区域覆盖率显著减少。与没有用CSM处理的样品相比，CSM的添加也引起在生长99小时之后生物膜细胞簇的平均厚度显著降低(图18)。实施例9-铜绿假单胞菌(P.aeruginosa)CSM和顺-2-癸烯酸的光谱分析
将在纯化水中制备的所有CSM样品均冻干，并再悬浮于用于各光谱分析的合适载体中。在所有试验中的CSM对照均由CSMHPLC产物和不含CSM的载体溶液组成，如微量滴定板分散生物测定所测定的，该CSM HPLC产物不诱导分散。实施例10-质谱分析
使样品再悬浮于载体溶液(50％水、50％甲醇和0.01％甲酸)中。使用高效、混合四极飞行时间质谱仪-
Figure G2008800246911D00321
XL混合LC/MS/MS系统(Applied Biosystems，Foster City，CA，USA)-以阳离子模式，在室温下，配有API 150EXTM、API 3000TM和系统(AppliedBiosystems)的IonSpray源，来进行质谱分析。使用Analyst QS 1.1版分析数据。实施例11-核磁共振(NMR)
使CSM和顺-2-癸烯酸样品再悬浮于1mL的氘代乙腈中，并插入薄壁的NMR样品管(VWR)内。用300MHz质子NMR-Bruker AC300(Bruker Daltonics Inc.，Vilarica，MA，USA)进行分析。使图谱累积24小时。实施例12-气相色谱-质谱(GC-MS)
将CSM和浓度为0.01mg×mL-1-10mg×mL-1的顺-2-癸烯酸样品再悬浮于2mL的乙腈中。进行3步连续己烷萃取以除去可溶性有机样品物质。将己烷在水浴(55-70℃)中蒸发至干。接着将Puridine(250μL)添加至可溶性样品，以便注射至GC中。用Shimadzu QP5050AGC-MS系统，使用氦作为载体和Restek(Columbia，MD)XTI-5GC柱(30m，0.25mm内径，0.25μm膜厚)，1mL×min-1流速，获得图谱。所有分析均结合不分流注射和电子碰撞电离。GC和MS之间的界面温度维持在310℃。使用程序Lab Solutions，GCMS解决方案1.2版来分析数据。实施例13-红外光谱(IR)
在冻干前和后称重CSM样品和顺-2-癸烯酸样品，以确定添加到各样品中的KBr的量。KBr以样品质量的10倍添加，并使用研钵和研杵混合。使用Carver 4350人工压丸机(Carver Inc.，Wabash，IN，USA)将得到的粉末形成小丸。施加10吨的压力，持续10min。按1cm-1的分辨率，在3500cm-1-400cm-1范围内，在室温下，使用Bruker Equinox55FT-IR分光计，获得IR图谱。最终的图谱表示128次扫描的平均值。各样品均一式三份测量。实施例14-生物膜细菌对抗生素抗药
图1A图示说明生物膜细菌如何对添加的抗生素抗药，与生物杀灭剂和其它抗微生物处理显示的抗性相似。图1B阐述了如果除抗生素以外还添加分散诱导剂，那么被分散的细菌就会失去它们的抗性且变得对抗生素敏感。实施例15-诱导分散的化合物的影响
图2显示实际生物膜样品，该样品用本发明的诱导分散的化合物处理，得自铜绿假单胞菌(Pseudomonas aeruginosa)的培养物。在该实验中，在用添加的CSM试验前，使用单程流动池培养铜绿假单胞菌(P.aeruginosa)6天。
流动池由阳极化处理的铝构成，包含用玻璃盖玻片盖住的室1.0mm×1.4cm×4.0cm。使用Masterflex 8辊头蠕动泵，以0.13mlmin-1的流速，使无菌EPRI培养基从2升的容器通过聚硅氧烷管泵送到流动池。流过室的是雷诺数为0.17的层流，流体停留时间是4.3min。离开流动池的培养基经聚硅氧烷管排放至流出物贮器。整个系统对外部环境关闭，但通过固定至各容器的0.2μm孔径可透气的过滤器来保持与大气压平衡。在流动条件下，穿过从流动池开始上游的4厘米隔膜，以3.0mL块剂量，接种对数期铜绿假单胞菌(P.aeruginosa)(约108CFU/ml)。使用Olympus BX60显微镜和放大50倍的ULWD MSPlan长焦点距离Olympus物镜，通过透射光观察附着至玻璃盖玻片内表面的细胞。使用Magnafire冷却型3芯片电荷耦合器件(CCD)照相机(OptronicsInc.，Galena，Calif.)捕获所有的图像，并存储为各数字化文件，用于以后检索和分析。在成熟的生物膜在流动池内发育之后，停止培养基流动，并将3mL的过滤CSM/无菌EPRI培养基添加至流动池。在用CSM处理前和期间取得在流动池内单个位置的透射光图像。图2显示在添加CSM前1min，在添加CSM之后5min，和在添加CSM之后30min，从该实验取得的图像。对照样品也以与试验样品同样的方式操作，不同之处在于6mL添加的EPRI培养基中不包括CSM。对照样品的结果显示生物膜细胞数量或生物膜结构没有变化，并且没有明显的分散。实施例16-生物膜细菌经过表型转换
在正常的生物膜发育过程中，生物膜细菌在成熟II期末经历表型的转变(图3)，其中它们在生理上从主要生物膜的形式变成主要浮游生物的形式。在分散相期间生物膜的显微镜观察证明，细胞簇内的细菌变得能动(成熟期铜绿假单胞菌(P.aeruginosa)是不动的)，而簇边缘周围的细菌保持固定。细菌可以在其中游动/颤动的细胞簇区域从(通常)中央位置容积生长，且最后在簇壁中造成裂口。细菌能够游过该裂口并进入大量液相，在细胞簇内留下空隙。
对分散响应的继续研究显示，细胞簇通过生长和分散的偶发事件而转变；相同的细胞簇常常经受许多这样的循环。多个分散和再生长事件一般导致细胞簇以类似于生长轮的模式发育，该生长轮可以显示分散已经发生的次数。通常，细胞簇将在分散事件期间完全地从基底膜分离(Stoodley等，″细胞簇从成熟混合种类的生物膜的生长和分离″Appl.Environ.Microbiol.67：5608-5613(2001)，该文献通过引用而整体结合到本文中)。该结果认为是由于在细胞簇的基部，附着结构的减弱所致，该细胞簇允许流体完全分离簇。实施例17-在培养基停滞之后的细胞分离
图4描述了相衬显微照片的时间序列，显示在培养基停滞72小时之后细胞的分离。按照在上面的实施例3中所述的方法，用铜绿假单胞菌(P.aeruginosa)PAO1接种到流动池，且培养3天。选择这些生物膜培养3天是基于以下观察：在连续的流动下，在温育了9天之后，观察到铜绿假单胞菌(P.aeruginosa)生物膜内的细胞簇经历了自发的分散事件。在连续的流动下生长72天之后，停止培养基流动且在96小时内每2小时记录细胞簇的图像。在培养基停滞72小时之后，观察到流动池内的细胞簇解聚，并且细胞作为悬浮细菌进入批量液体培养基中(图4)。这些实验表明，停止流动诱导生物膜的分散响应。在这些实验中，分散不是简单地发生在细胞簇内，而是遍及生物膜中的所有簇。如图4所示，观察到只有直接附着于基底膜的那些细胞才没有游入批量液体内。实施例18-氯仿提取方法的开发
试验了各种生长和提取方法，以开发提取具有分散诱导活性的用过培养基活性部分的可靠方法。选择氯仿作为选择的提取溶剂，是由于它与HPLC分级分离程序的相容性，因为它导致窄范围的可提取有机化合物(通过质谱法测定)和因为它能够恢复生物活性量的分散诱导剂。目前用于氯仿提取用过培养基的方法如下：铜绿假单胞菌(P.aeruginosa)PAO1的细菌培养物在4升的EPRI培养基(包含：乳酸钠0.05g/l、琥珀酸钠0.05g/l、硝酸铵50.381g/l、KH2PO4 0.19g/l、K2HPO4 0.63g/l、Hutner金属盐溶液1ml和葡萄糖2.0g/l)中，在分批培养容器中，在室温下连续搅拌下生长6天。在生长后，通过在10,000×g下离心20分钟，从培养基中除去细菌，然后通过0.22μm孔径的过滤器将用过培养基过滤。分批使250ml的过滤的用过培养基与80ml的氯仿在分液漏斗中混合。在分离10分钟之后除去氯仿部分。然后用旋转蒸发器R-3000(Biichi Laboratories，Flawil，Switzerland)使氯仿样品在70℃下蒸发至干，并再悬浮于6mL的过滤的纳米纯水或EPRI培养基中。得自氯仿提取操作的最终产物在此处称为浓缩的用过培养基或CSM。图15显示比较CSM与用过培养基对生长在生物膜管状反应器中的连续培养生物膜的影响的结果。如先前所述，由在22℃下，在补充2.0克/升葡萄糖的EPRI培养基中生长9天的铜绿假单胞菌(P.aeruginosa)PAO1的培养物来制备CSM和用过培养基。在由32cm二氧化硅Masterflex 14号管组成的生物膜管状反应器中，在22℃下，将铜绿假单胞菌(P.aeruginosa)PAO1的生物膜培养6天。在第6天末，将6mL的各自补充2.0克/升葡萄糖的CSM、用过培养基或无菌的EPRI培养基添加至管中。在20分钟时间内，将各处理的管流出物收集并合并。测定合并的样品在570nm的光密度，以测定从各处理分散的相对细胞数。各实验重复进行5次。这些实验的结果证明，与用过培养基相比，氯仿提取的用过培养基、CSM在分散铜绿假单胞菌(P.aeruginosa)的生物膜中显示了更大的活性。
申请人观察到，在培养基流动已经停止几个小时之后，铜绿假单胞菌(P.aeruginosa)PAO1将从连续培养生物膜中分散，该生物膜生长在流动池反应器内玻璃基底膜上。该观察导致以下假设：生物膜的分散可因用作生物膜解聚诱导剂的细胞外信使的积聚引起。以下的观察支持该假设：铜绿假单胞菌(P.aeruginosa)的生物膜在分批培养瓶中将不形成，但将在恒化器的壁上形成，这表明分散信号的积累可防止生物膜的发育。此外，当铜绿假单胞菌(P.aeruginosa)的微集落按连续培养生长时，当它们达到40微米的最小直径和10微米的厚度时，将在它们的中央形成空洞(图6)。然而，在其中形成这些空隙的微集落尺寸取决于液体的流速。当生物膜反应器中的流动增快时，出现微集落空隙形成的直径和厚度也增大，这表明了分散诱导与传输之间的关系。这些观察结果暗示，由铜绿假单胞菌(P.aeruginosa)产生的细胞外物质对诱导生物膜分散起作用。
如果铜绿假单胞菌(P.aeruginosa)产生胞外诱导分散的化合物，则申请人推测将无细胞的用过培养基添加至成熟的铜绿假单胞菌(P.aeruginosa)生物膜应该引起细胞释放到大量的液体培养基中。当在反应器流出物中回收的细胞数量增加时，应该可检测到这些细菌。图7A描述了代表性的实验结果，其中生物膜在连续的流动下，用无细胞用过培养基处理70分钟，铜绿假单胞菌(P.aeruginosa)已经在该无细胞用过培养基中悬浮生长24小时；添加新鲜培养基以控制生物膜。在添加前，将用过培养基充气，补充葡萄糖并调节其pH至中性，以保证饥饿、氧气耗尽或pH的变化不对细菌的释放起作用。在添加用过培养基的20分钟内，与对照系相比，在流出的细胞数量中可检测到大的尖峰，表明生物膜细菌释放至用用过培养基处理的培养物的流出物内。在对照样品中也可检测到释放细胞的小的尖峰，可能表示对物理或机械作用的反应，该物理或机械作用与系转换至新鲜培养基贮器有关。
为了纯化用过培养基的活性分散诱导部分，使用氯仿提取铜绿假单胞菌(P.aeruginosa)的无细胞稳定期分批培养物，然后旋转蒸发氯仿，并使有机部分再悬浮于新鲜培养基或缓冲溶液中(导致氯仿可溶性有机部分增加125倍)。该制剂被称为CSM。为了测试CSM的分散诱导活性，使铜绿假单胞菌(P.aeruginosa)生物膜在聚硅氧烷管内按连续培养生长，并使生物膜暴露至用CSM改良的培养基中，持续1小时。在用新鲜培养基处理的对照系中，管状反应器的挤出的内容物显示大量完整的生物膜(图7B)，而用CSM处理的管的内容物显示生物膜已经完全解聚(图7C)。在聚硅氧烷管内按连续培养生长的4天老生物膜的研究显示，通过释放至流出物的集落形成单位测定，用含CSM的培养基处理1小时有效释放平均87.4％(±1.4％)的生物膜细胞。显示用过培养基的平均分散效力为32.4％(±5.5％)。
显微镜检查法用于评估CSM对生物膜微集落的影响，该生物膜微集落在安装至显微镜的流动池的玻璃基底膜上按连续培养生长6天(K.Sauer等，J.Bacteriol.184：1140(2002)，该文献通过引用而整体结合到本文中)。在添加CSM前，观察到发育良好的微集落包含固定并显示无活动迹象的细胞(图7D)。在与含CSM的培养基接触7分钟之后，微集落内的细胞开始颤动并显示积极的活动(图7E)。在30分钟后，微集落已经变得完全解聚，观察到细胞穿过培养基自由地游动(图7F)。当与自然分散比较时，观察到外源性诱导的分散从微集落的外部朝内部发展，而不是形成中央空隙，导致微集落的完全解聚。
当向流动池连续添加时，CSM调节用过培养基的浓度，显示在99小时的时间内显著抑制生物膜的发育，证明生物膜的平均厚度和表面积覆盖率均降低(图8)。在从第1天(生物膜微集落形成开始)到第6天的所有时间点，均可测量CSM对预先形成的生物膜的外源性分散诱导，在这期间之后开始发生自然分散。当冷冻下储藏时，CSM的活性显示持续长达6个月，而无明显的降低。通过乙酸乙酯提取用过培养基(以回收酰基-高丝氨酸内酯)不会产生具有分散活性的制剂。
由于已经证明了对铜绿假单胞菌(P.aeruginosa)形成的成熟和发育的生物膜的分散诱导，因此在下面测试在大肠杆菌(E.coli)的生物膜培养物、与铜绿假单胞菌(P.aeruginosa)混合的大肠杆菌(E.coli)生物膜培养物、源自空气传播污染物的未定义的混合细菌生物膜和对肺炎克雷伯氏菌(Klebsiella pneumoniae)、奇异变形杆菌(Proteusmirabilis)、化脓性链球菌(Streptococcus pyogenes)、枯草芽孢杆菌(Bacillus subtilis)、金黄色葡萄球菌(Staphylococcus aureus)和白色念珠菌(Candida albicans)形成的生物膜中，CSM诱导分散的能力。与对照相比，CSM在所有测试的样品中均显示出刺激显著的分散。这些实验的结果如图9中所示。在不同属的细菌和在酵母中，铜绿假单胞菌(P.aeruginosa)分散诱导剂激活分散的能力显示，它具有跨门和跨界的活性。
由于已经确定了CSM作为生物膜分散诱导剂的作用，因此鉴定了存在于CSM中的一种或多种活性分子。这由测定CSM的多个部分的分散活性开始，所述部分使用C-18反相高效液相色谱(HPLC)，通过乙腈和水的等度梯度分离。洗脱的HPLC流份(按1分钟时间间隔收集)在Speedvac中干燥，以除去残留的乙腈，再悬浮于纯化水中，并通过微量滴定板分散生物测定法来测试，以确定分散活性。图10A显示CSM分级分离生物膜分散测定的结果。结果显示，由比例为70％/30％的乙腈/水，在22分钟洗脱的CSM的HPLC流份显示最高的活性。
活性HPLC CSM流份的质谱显示在171M/Z(mw＝170)的具有低离子化活性的一致分子峰。该峰存在于所有显示分散活性的样品中，而在所有缺少分散活性的样品中没有。该峰也显示在用于制备CSM(包括新鲜培养基)的所有载液和溶剂中没有。170mw峰的质谱-产物离子分析、溶解度分析、H1-和C13核磁共振(NMR)光谱和红外(IR)光谱已经证明，170mw分子是双键位于2位碳的单不饱和C10-脂肪酸；2-癸烯酸。
为了证实22分钟CSM HPLC流份的170-mw分子(M/Z＝171)与2-癸烯酸相同，使原始分子在质谱中变成碎片，以产生产物离子峰。用四极ms/ms分析活性CSM流份和2-癸烯酸的产物离子，以评估这两个分子之间的裂解差异。图12A显示171M/Z CSM样品与2-癸烯酸具有同一性。当用GC-MS分析时，未分离的CSM显示单一主峰，保留时间为7.6分钟，其与图12B中2-癸烯酸的相同。红外光谱证实2-癸烯酸的顺式异构体是从CSM分离的有机化合物，见图12C。
在该鉴别之后，合成各种分子量的单不饱和脂肪酸分子，并测试这些分子的分散活性。显示破坏野油菜黄单胞菌(X.campestris)的细胞絮凝物的DSF显示没有促进铜绿假单胞菌(P.aeruginosa)的分散。具有最高活性的化合物是2-癸烯酸的两种异构体。通过微量滴定板分散生物测定显示反式异构体(反-2-癸烯酸)仅在毫摩尔浓度才有活性，通常没有低的足以有资格作为细胞-细胞信号分子。图10B显示增加浓度的顺-2-癸烯酸对生长在微量滴定板中的铜绿假单胞菌(P.aeruginosa)生物膜培养物的分散活性。这些结果证明，顺式异构体(顺-2-癸烯酸)在1.0纳摩尔-10毫摩尔的浓度范围内有活性，在1.0纳摩尔显示比未浓缩的用过培养基更大的分散活性(即高于天然存在的诱导剂)。显微镜检查显示顺-2-癸烯酸作为分散诱导剂的活性与CSM活性相似，如图13中所示，完全破坏生物膜微集落。也测试顺-2-癸烯酸对大肠杆菌(E.coli)、肺炎链球菌(S.pneumonia)、奇异变形杆菌(P.mirabilis)、化脓性链球菌(S.pyogenes)、枯草芽孢杆菌(B.subtilis)、金黄色葡萄球菌(S.aureus)和白色念珠菌(C.albicans)生物膜培养物的活性，得到与CSM获得的那些相似的结果(图11)。
该研究显示，在分批和生物膜培养中由铜绿假单胞菌(P.aeruginosa)产生小信使脂肪酸分子顺-2-癸烯酸。已经证明该分子在铜绿假单胞菌(P.aeruginosa)形成的生物膜内和在革兰氏阴性和革兰氏阳性菌的范围内以及在酵母内诱导分散响应。分散响应是在群体内逃脱饥饿状态的机制，允许固定细胞有机会迁移到更有利的环境，并使剩余的群体稀疏，允许细胞获得增加的营养物。当生物膜微集落很小时，在细胞外基质中积聚的诱导剂通过扩散和对流转运除去。该除去在分批系统中是不可能的。当细胞簇达到其中诱导剂不能从内部充分洗出的尺寸时(扩散的速率被产生的速率超过)，诱导剂能够达到激活分散响应，从生物膜释放细胞所需的浓度。细胞-细胞信号分子对生物膜分散起作用的发现允许外源性诱导生物膜细菌转变至悬浮状态。在抗生物膜相关的感染和控制微生物生物结垢中，该分散诱导剂的使用可能导致增强的处理选项。
虽然本文已经详细地描绘和描述了优选的实施方案，但是对相关领域的技术人员来讲，可以进行各种修改、添加、替换等，而不背离本发明的精神将是显而易见的，这些修改、添加、替换等因此认为是在本发明的范围内，本发明的范围在权利要求中限定。

Claims (109)

1.一种组合物，所述组合物包含：
一种或多种分散诱导剂，所述分散诱导剂包含：
Figure F2008800246911C00011
其中
Figure F2008800246911C00012
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中所述酯或酰胺是所述羧酸的电子等排体或生物等排体，和
一种或多种添加剂组分，所述添加剂组分选自生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物，将所述组合物配制成使其当与由微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，所述分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应，以将所述生物膜破坏。
2.权利要求1的组合物，其中所述分散诱导剂包含：
CH3-(CH2)n-CH＝CHCOOH。
3.权利要求1的组合物，其中所述分散诱导剂包含：
Figure F2008800246911C00013
4.权利要求1的组合物，其中所述分散诱导剂包含：
Figure F2008800246911C00014
5.权利要求1的组合物，其中R选自：
Figure F2008800246911C00021
6.权利要求1的组合物，其中R是高丝氨酸内酯或呋喃酮基团。
7.权利要求1的组合物，其中所述分散诱导剂以1μM-30mM的浓度存在于所述组合物中。
8.权利要求1的组合物，其中所述分散诱导剂是顺式异构体。
9.权利要求1的组合物，所述组合物的pH为1.5-4.5。
10.权利要求1的组合物，所述组合物的pH为4.5-8.0。
11.权利要求1的组合物，所述组合物的pH为6.8-7.4。
12.权利要求1的组合物，所述组合物的pH为8.0-9.8。
13.权利要求1的组合物，其中所述分散诱导剂具有不多于15个碳原子。
14.权利要求1的组合物，所述组合物是洁齿剂或漱口剂。
15.权利要求1的组合物，其中将所述组合物配制成使所述分散诱导剂是非杀菌的。
16.权利要求1的组合物，其中所述分散诱导剂以小于0.5％重量的浓度存在于所述组合物中。
17.权利要求1的组合物，所述组合物基本上不含乙醇。
18.权利要求1的组合物，所述组合物基本上不含甲醛。
19.权利要求1的组合物，所述组合物包含外科用胶。
20.一种表面，所述表面用权利要求1的组合物涂布。
21.权利要求20的表面，所述表面是牙线。
22.权利要求20的表面，所述表面是接触透镜。
23.权利要求20的表面，所述表面是骨植入物。
24.一种治疗或预防受试者中由生物膜介导的病症的方法，所述方法包括：
提供受试者，该受试者具有或易感由生物膜介导的病症，该生物膜由微生物产生，因此所述生物膜在表面上包含基质和微生物；和
在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予所述受试者，所述分散诱导剂包含：
Figure F2008800246911C00031
其中
Figure F2008800246911C00032
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中所述酯或酰胺是所述羧酸的电子等排体或生物等排体，因此治疗或预防了受试者中由生物膜介导的病症。
25.权利要求24的方法，所述方法还包括：
将抗微生物处理与分散诱导剂的所述给予联合给予受试者，所述抗微生物处理选自以下处理中的一种或多种：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、超声波处理、放射处理、热处理和机械处理。
26.权利要求24的方法，其中治疗烧伤的受试者。
27.权利要求24的方法，其中治疗患有牙斑、龋齿、齿龈疾病和/或口腔感染的受试者。
28.权利要求27的方法，其中所述给予用洁齿剂、漱口剂、牙线、胶、条状物或刷子进行。
29.权利要求24的方法，其中治疗在皮肤上有痤疮或其它生物膜相关的皮肤感染的受试者。
30.权利要求24的方法，其中治疗患有慢性生物膜相关疾病的受试者。
31.权利要求30的方法，其中所述慢性生物膜相关疾病选自中耳感染、骨髓炎、前列腺炎、囊性纤维化、结肠炎、阴道炎、尿道炎和胃溃疡或十二指肠溃疡。
32.权利要求24的方法，其中所述分散诱导剂以0.01μM-30mM的浓度给予。
33.权利要求24的方法，其中所述分散诱导剂以pH为1.5-4.9的组合物给予。
34.权利要求24的方法，其中所述分散诱导剂以pH为4.5-8.0的组合物给予。
35.权利要求24的方法，其中所述组合物的pH为6.8-7.4。
36.权利要求24的方法，其中所述组合物的pH为8.0-9.8。
37.权利要求24的方法，其中所述分散诱导剂具有不多于15个碳原子。
38.权利要求24的方法，其中所述分散诱导剂是顺式异构体。
39.权利要求24的方法，其中所述分散诱导剂以组合物给予，该组合物配制成使所述分散诱导剂为非杀菌的。
40.权利要求24的方法，其中所述分散诱导剂以小于0.5％重量的浓度给予。
41.一种处理或抑制表面上生物膜形成的方法，所述方法包括：
提供具有或易感生物膜形成的表面，该生物膜由微生物产生，因此该生物膜在表面上包含基质和微生物；和
在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物效应的条件下，将分散诱导剂给予所述表面，所述分散诱导剂包含：
Figure F2008800246911C00051
其中
Figure F2008800246911C00052
是碳-碳单键或双键，m是1或2，n是2-15，且R是羧酸、盐、酯或酰胺，其中所述酯或酰胺是所述羧酸的电子等排体或生物等排体，
因此处理或抑制了表面上生物膜的形成。
42.权利要求41的方法，其中所述表面是接触透镜。
43.权利要求41的方法，其中所述表面是选自以下的留置医疗装置：导管、呼吸器和通风器。
44.权利要求41的方法，其中所述表面是选自以下的植入医疗装置：支架、人工瓣膜、关节、缝合线、U形钉、起搏器、骨植入物和钉。
45.权利要求41的方法，其中所述表面选自排泄装置、桶状物、厨房用具、工作台面、淋浴帘、薄浆、盥洗室、工业食品和饮料生产设施、地板和食品加工设备。
46.权利要求41的方法，其中所述表面是热交换器表面或过滤器表面。
47.权利要求41的方法，其中所述表面是选自以下的海上构筑物：船、桥墩、石油平台、水摄取口、筛和观察口。
48.权利要求41的方法，其中所述表面与水处理和/或分配系统相联系。
49.权利要求47的方法，其中所述水处理和/或分配系统选自饮用水处理和/或分配系统、池和矿泉水处理系统、制备操作中的水处理和/或分配系统和牙科水处理和/或分配系统。
50.权利要求41的方法，其中所述表面与提取石油的石油钻探、贮藏、分离、精制、分配和/或多孔介质的系统相联系。
51.权利要求49的方法，其中所述石油钻探、贮藏、分离和/或分配的系统选自石油分离列车、石油容器、石油分配管道和石油钻探设备。
52.权利要求41的方法，所述方法还包括：
将至少一种抗微生物处理与分散诱导剂的所述给予联合给予所述表面，所述抗微生物处理选自生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、超声波处理、放射处理、热处理和机械处理。
53.权利要求52的方法，其中所述分散诱导剂和所述抗微生物处理同时给予。
54.权利要求52的方法，其中所述分散诱导剂和抗微生物处理分别给予。
55.权利要求52的方法，其中将所述分散诱导剂浸渍在所述表面中。
56.权利要求52的方法，其中所述分散诱导剂以涂布所述表面的共聚物或凝胶给予。
57.权利要求52的方法，其中所述分散诱导剂以0.01μM-30mM的浓度给予。
58.权利要求52的方法，其中所述组合物以pH为1.5-4.9的组合物给予。
59.权利要求58的方法，其中所述组合物以pH为4.5-8.0的组合物给予。
60.权利要求52的方法，其中所述组合物的pH为6.8-7.4。
61.权利要求52的方法，其中所述组合物的pH为8.0-9.8。
62.权利要求41的方法，其中所述分散诱导剂具有不多于15个碳原子。
63.权利要求41的方法，其中所述分散诱导剂是顺式异构体。
64.权利要求41的方法，其中所述分散诱导剂以组合物给予，该组合物配制成使所述分散诱导剂为非杀菌的。
65.权利要求41的方法，其中所述分散诱导剂以小于0.5％重量的浓度给予。
66.权利要求41的方法，其中所述表面是骨植入物。
67.一种溶液，所述溶液包含：
分散诱导剂，所述分散诱导剂包含：
Figure F2008800246911C00071
其中
Figure F2008800246911C00072
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸，其中所述诱导剂以小于0.5％重量的浓度存在，且其中所述溶液的pH大于5。
68.权利要求67的溶液，其中所述分散诱导剂包含：
CH3-(CH2)n-CH＝CHCOOH。
69.权利要求67的溶液，其中所述分散诱导剂包含：
Figure F2008800246911C00073
70.权利要求67的溶液，其中所述分散诱导剂包含：
Figure F2008800246911C00074
71.权利要求67的溶液，所述溶液不含乙醇。
72.权利要求67的溶液，所述溶液不含甲醛。
73.权利要求67的溶液，其中所述pH基本上呈中性。
74.权利要求67的溶液，所述溶液选自皮肤软膏剂、牙膏和漱口剂。
75.权利要求67的溶液，其中所述诱导剂配制成非盐形式。
76.权利要求67的溶液，所述溶液还包含选自以下组分中一种或多种的组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物。
77.一种组合物，所述组合物包含：
选自以下组分中一种或多种的组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物，和
具有下式的分散诱导剂：
Figure F2008800246911C00081
其中
Figure F2008800246911C00082
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸，所述诱导剂配制成非盐形式。
78.权利要求77的组合物，其中所述分散诱导剂包含：
CH3-(CH2)n-CH＝CHCOOH。
79.权利要求77的组合物，其中所述分散诱导剂包含：
Figure F2008800246911C00083
80.权利要求77的组合物，其中所述分散诱导剂包含：
Figure F2008800246911C00084
81.权利要求77的组合物，所述组合物是基本上不含乙醇的溶液。
82.权利要求81的组合物，其中所述溶液也基本上不含甲醛。
83.权利要求81的组合物，其中所述溶液基本上为pH中性。
84.权利要求77的组合物，所述组合物为选自以下的制剂：皮肤软膏剂、牙膏和漱口剂。
85.一种溶液，所述溶液包含：
2-癸烯酸的顺式异构体，其中所述溶液选自皮肤软膏剂、牙膏和漱口剂，且其中所述溶液基本上不含2-癸烯酸的反式异构体。
86.一种溶液，所述溶液包含：
2-癸烯酸的顺式异构体，其中所述溶液选自皮肤软膏剂、牙膏和漱口剂，且其中所述溶液不含反式异构体。
87.一种方法，所述方法包括：
a)提供接触透镜和溶液，所述溶液包含浓度小于0.5％重量的分散诱导剂，所述诱导剂包含：
其中是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸、盐、酯或酰胺，其中所述酯或酰胺是所述羧酸的电子等排体或生物等排体；和
b)用所述溶液处理所述接触透镜。
88.权利要求87的方法，其中所述分散诱导剂包含：
CH3-(CH2)n-CH＝CHCOOH。
89.权利要求87的方法，其中所述分散诱导剂包含：
90.权利要求87的方法，其中所述分散诱导剂包含：
91.权利要求87的方法，其中所述溶液基本上不含乙醇。
92.权利要求87的方法，其中所述溶液基本上不含甲醛。
93.权利要求87的方法，其中所述溶液的所述pH基本上呈中性。
94.权利要求87的方法，其中所述接触透镜贮藏在所述溶液中。
95.权利要求87的方法，其中将所述诱导剂配制成非盐形式。
96.权利要求87的方法，其中所述溶液还包含选自以下的至少一种组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂和毒力因子抑制剂。
97.一种方法，所述方法包括：
a)提供患有皮肤病的受试者和pH大于5的溶液，所述溶液包含浓度小于0.5％重量的分散诱导剂，所述诱导剂包含：
其中
Figure F2008800246911C00102
是碳-碳单键或双键，m是1或2，n是4-7，且R是羧酸、盐、酯或酰胺，其中所述酯或酰胺是所述羧酸的电子等排体或生物等排体；和
b)用所述溶液治疗所述皮肤病。
98.权利要求97的方法，其中所述分散诱导剂包含：
CH3-(CH2)n-CH＝CHCOOH。
99.权利要求95的方法，其中所述分散诱导剂包含：
Figure F2008800246911C00103
100.权利要求97的方法，其中所述分散诱导剂包含：
Figure F2008800246911C00104
101.权利要求97的方法，其中所述溶液基本上不含乙醇。
102.权利要求97的方法，其中所述溶液基本上不含甲醛。
103.权利要求97的方法，其中所述溶液的所述pH基本上呈中性。
104.权利要求97的方法，其中将所述溶液配制成软膏。
105.权利要求97的方法，其中将所述诱导剂配制成非盐形式。
106.权利要求97的方法，其中所述溶液还包含选自以下的至少一种组分：生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂和毒力因子抑制剂。
107.一种组合物，所述组合物包含：
一种或多种分散诱导剂，和
一种或多种添加剂组分，所述添加剂组分选自生物杀灭剂、表面活性剂、抗生素、防腐剂、去污剂、螯合剂、毒力因子抑制剂、凝胶、聚合物、糊、可食用产物和可咀嚼产物，所述组合物被配制成使其当与由微生物产生的生物膜接触时，其中该生物膜在表面上包含基质和微生物，所述分散诱导剂选择性地作用于所述微生物并具有合适的生物反应，不需要直接作用使所述基质破坏。
108.一种治疗或预防受试者中由生物膜介导的病症的方法，所述方法包括：
提供具有或易感由生物膜介导的病症的受试者，该生物膜由微生物产生，因此所述生物膜在表面上包含基质和微生物；和
在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予所述受试者，因此治疗或预防了所述受试者中由生物膜介导的病症。
109.一种处理或抑制表面上生物膜形成的方法，所述方法包括：
提供具有或易感生物膜形成的表面，该生物膜由微生物产生，因此该生物膜在表面上包含基质和微生物，和
在有效的使分散诱导剂不需要对基质直接作用，而选择性地作用于所述微生物并具有合适的生物反应的条件下，将分散诱导剂给予所述表面，因此处理或抑制了在所述表面上生物膜的形成。
CN200880024691.1A 2007-05-14 2008-05-14 生物膜中细菌细胞内的生理学分散响应诱导 Active CN101801521B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US91779107P 2007-05-14 2007-05-14
US60/917,791 2007-05-14
US1863908P 2008-01-02 2008-01-02
US61/018,639 2008-01-02
PCT/US2008/006171 WO2008143889A1 (en) 2007-05-14 2008-05-14 Induction of a physiological dispersion response in bacterial cells in a biofilm

Publications (2)

Publication Number Publication Date
CN101801521A true CN101801521A (zh) 2010-08-11
CN101801521B CN101801521B (zh) 2015-06-17

Family

ID=40122044

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200880024691.1A Active CN101801521B (zh) 2007-05-14 2008-05-14 生物膜中细菌细胞内的生理学分散响应诱导

Country Status (9)

Country Link
US (3) US8513305B2 (zh)
JP (1) JP5548121B2 (zh)
CN (1) CN101801521B (zh)
BR (1) BRPI0811530B1 (zh)
CA (1) CA2684150C (zh)
DE (1) DE112008001301T5 (zh)
DK (1) DK200970201A (zh)
GB (1) GB2463181B (zh)
WO (1) WO2008143889A1 (zh)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104056820A (zh) * 2014-05-12 2014-09-24 曹俊彪 耳鼻喉科用内镜消毒装置
CN106390201A (zh) * 2016-09-21 2017-02-15 天津欧尔克医药科技有限公司 一种可吸收医用生物膜及其制备方法
CN110229763A (zh) * 2019-04-30 2019-09-13 宁波大学 一株絮凝剂生产菌及其在对虾生物絮团养殖和染料脱色中应用
CN110573192A (zh) * 2017-01-05 2019-12-13 科医公司 针对成熟生物膜有效的包括抗微生物水凝胶的抗微生物组合物
CN116903155A (zh) * 2023-09-13 2023-10-20 上海同济工程咨询有限公司 一种水质改良剂及其制备方法、水体养护方法

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070207095A1 (en) * 2005-12-09 2007-09-06 Research Foundation Of State University Of New York Induction of a physiological dispersion response in bacterial cells in a biofilm
GB2463181B (en) 2007-05-14 2013-03-27 Univ New York State Res Found Induction of a physiological dispersion response in bacterial cells in a biofilm
EP2387376A4 (en) * 2009-01-19 2014-04-23 Cochlear Ltd SURFACE CHANGE FOR IMPLANTABLE MEDICAL DEVICE
US9591852B2 (en) 2009-11-23 2017-03-14 Mcneil-Ppc, Inc. Biofilm disruptive compositions
JP2012097037A (ja) * 2010-11-02 2012-05-24 Kao Corp オートインデューサー−２阻害剤、並びに歯骨炎又は齲蝕病の予防及び／又は治療剤
WO2013052010A1 (en) * 2011-10-03 2013-04-11 Agency For Science, Technology And Research Antibiotic composition and its uses
JPWO2014017233A1 (ja) * 2012-07-27 2016-07-07 住友重機械工業株式会社 微生物用活性調節剤及び微生物の活性を調節する方法
US20160113940A1 (en) 2013-09-03 2016-04-28 Biomimetix J.V., Llc Methods of treating biofilms
US10597314B2 (en) * 2013-11-22 2020-03-24 General Electric Company Fatty acid biodispersant and methods of use
JP2015155534A (ja) * 2014-01-17 2015-08-27 住友重機械工業株式会社 バイオフィルム分解剤及びバイオフィルムの分解方法
WO2015112586A1 (en) 2014-01-22 2015-07-30 Duke University Methods of treating pruritus
WO2015112588A1 (en) 2014-01-22 2015-07-30 Biomimetix Jv, Llc Methods of treating skin disorders
JP6619544B2 (ja) * 2014-03-19 2019-12-11 株式会社日立ハイテクノロジーズ 検査装置
KR101724655B1 (ko) * 2014-06-02 2017-04-13 주식회사 아모라이프사이언스 마이크로 니들 패치 및 그의 제조 방법
CN107847427B (zh) * 2015-07-14 2021-08-06 Wm.雷格利Jr.公司 作为用于从口腔优先去除革兰氏阴性菌的疏水配体的木兰树皮提取物
WO2017044212A1 (en) * 2015-09-11 2017-03-16 Jivan Vinay Tongue cleaner with a mouth freshener disinfecting strip
EP3614842A4 (en) 2017-04-29 2021-02-24 Nevada Naturals, Inc. BIOFILM PENETRATING COMPOSITIONS AND PROCESSES
US11541105B2 (en) 2018-06-01 2023-01-03 The Research Foundation For The State University Of New York Compositions and methods for disrupting biofilm formation and maintenance
KR20220015432A (ko) 2019-05-28 2022-02-08 브로민 콤파운드 리미티드 수처리를 위한 방법 및 조성물
AU2021233221A1 (en) 2020-03-09 2022-09-15 DePuy Synthes Products, Inc. Bactericidal debridement compositions for surgical site infections and chronic wound healing
EP4255882A1 (en) 2020-12-01 2023-10-11 Bromine Compounds Ltd. Preparation of cis-2-alkenoic acids
WO2022118312A1 (en) 2020-12-02 2022-06-09 Bromine Compounds Ltd. Method and composition for water treatment
WO2023238135A1 (en) 2022-06-08 2023-12-14 Bromine Compounds Ltd. Preparation and purification of cis-2-alkenoic acids

Family Cites Families (889)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4215144A (en) * 1972-08-25 1980-07-29 Oxford Hill Ltd. Method of treating and controlling gingivitis
DE2310246A1 (de) 1973-03-01 1974-09-12 Henkel & Cie Gmbh Verwendung ungesaettigter carbonsaeuren als antimikrobielle substanzen
US3936385A (en) 1973-08-09 1976-02-03 Colgate-Palmolive Company Denture cleanser
DE2349090A1 (de) 1973-09-29 1975-04-10 Henkel & Cie Gmbh Verwendung ungesaettigter carbonsaeuren in kombination mit formaldehyd als antimikrobielle mittel
US4097604A (en) * 1975-12-18 1978-06-27 Oxford Hill, Ltd. Method of treating and controlling gingivitis
JPS5495535A (en) 1978-01-06 1979-07-28 Nippon Zeon Co Ltd Production of ketone and lactone
US4442125A (en) * 1978-06-26 1984-04-10 Oxford Hill, Ltd. Process for detaching or preventing attachment of microorganisms to a surface
US4224307A (en) * 1978-06-26 1980-09-23 Oxford Hill, Ltd. Mouthwash and methods
US4214006A (en) * 1978-07-24 1980-07-22 Oxford Hill, Ltd. Mouthwash and method for preventing and removing dental plaque
US4257433A (en) 1980-01-22 1981-03-24 Well Men Industrial Co. Limited Water-driven toothbrush and water-pick assembly
JPS58213716A (ja) 1982-06-05 1983-12-12 Junichi Iwamura 制癌剤
JPS59193809A (ja) 1983-04-19 1984-11-02 Teijin Ltd 除草組成物
JPS59199606A (ja) 1983-04-27 1984-11-12 Teijin Ltd 除草剤
JPS609728A (ja) 1983-06-29 1985-01-18 Dainippon Printing Co Ltd 容器の成形方法
JPS61106501A (ja) 1984-10-30 1986-05-24 Teijin Ltd 除草組成物
US4978685A (en) 1986-09-24 1990-12-18 Great Lakes Chemical Corporation Control of biofouling in aqueous systems by non-polymeric quaternary ammonium polyhalides
US4976874A (en) 1987-04-20 1990-12-11 Great Lakes Chemical Corporation Control of biofouling in aqueous systems by non-polymeric quaternary ammonium polyhalides
US5061106A (en) 1988-03-08 1991-10-29 Colgate-Palmolive Company Toothbrush with slow release of disinfectant and antibacterial agents and method of manufacturing the same
US6270890B1 (en) 1988-03-29 2001-08-07 Colgate-Palmolive Company Dental floss
US4865545A (en) 1988-07-27 1989-09-12 Rocca Nina Dental aspirator
JPH02241546A (ja) 1989-03-14 1990-09-26 Japan Tobacco Inc 炭素一炭素二重結合の位置選択的水素添加用触媒
JPH0830171B2 (ja) 1989-08-17 1996-03-27 日本ペイント株式会社 溶剤型塗料組成物
IL94294A (en) 1990-05-04 1992-11-15 Hamivreshet Brush Factory Kibb Toothbrush
US5152686A (en) 1991-04-25 1992-10-06 Calvin Duggan Dental appliance
US5798117A (en) * 1992-04-24 1998-08-25 Biocompatibles Limited Method of reducing microorganism adhesion
DK1159974T3 (da) 1993-07-19 2007-11-26 Angiotech Pharm Inc Antiangiogene sammensætninger indeholdende taxol og en ikke-bionedbrydelig bærer og deres anvendelse
US6936447B1 (en) * 2000-04-03 2005-08-30 University Of Iowa Research Foundation Autoinducer molecule
JPH07173166A (ja) 1993-11-05 1995-07-11 Takeda Chem Ind Ltd Ｔａｎ−１６０７ａ誘導体、その製造法および用途
US5753180A (en) 1995-04-17 1998-05-19 Bio-Technical Resources Method for inhibiting microbially influenced corrosion
US6086921A (en) 1995-04-25 2000-07-11 Wintrop-University Hospital Metal/thiol biocides
US5645841A (en) 1995-06-05 1997-07-08 Whitehill Oral Technologies, Inc. Ultramulsion based oral care rinse compositions
EP0844864A1 (en) 1995-08-18 1998-06-03 Novo Nordisk A/S Tooth bleaching
WO1997026855A1 (en) 1996-01-24 1997-07-31 Warner-Lambert Company Peroxide/essential oils containing mouthwash compositions and two-part mouthwash systems
EP1001736A1 (en) 1996-10-11 2000-05-24 Novo Nordisk A/S STARCH BINDING DOMAINS (SBDs) FOR ORAL CARE PRODUCTS
JP4275751B2 (ja) 1996-12-27 2009-06-10 久光製薬株式会社 外用組成物
US6455031B1 (en) * 1997-06-18 2002-09-24 David G Davies Methods and compositions for controlling biofilm development
US5785523A (en) 1997-08-15 1998-07-28 Overmyer; Thad J. Dental water line flushing and disinfecting system
US6830745B1 (en) * 1997-10-16 2004-12-14 Pharmacal Biotechnologies, Llc Compositions for treating biofilm
AU1811499A (en) 1997-12-10 1999-06-28 Kolynos Do Brasil Ltda Dental floss
US6241994B1 (en) 1998-02-27 2001-06-05 Buckman Laboratories International, Inc. Solid TCMTB formulations
US5939051A (en) 1998-02-27 1999-08-17 Colgate-Palmolive Company Dental abrasive
US6106854A (en) 1998-03-25 2000-08-22 Belfer; William A. Disinfectant composition for infectious water and surface contaminations
US20030079758A1 (en) 1998-06-03 2003-05-01 Siegel Phyllis B. Process and composition for removing biofilm
US5968480A (en) 1998-07-09 1999-10-19 Colgate Palmolive Company Oral composition exhibiting enhanced antiplaque efficacy
US7229286B2 (en) 1998-07-10 2007-06-12 Jones Derek W Composite veneered cast glass-ceramic dental construct
IL142132A0 (en) 1998-09-23 2002-03-10 Phycogen Inc Methods and compositions for treating receptor mediated diseases
GB9913237D0 (en) * 1999-06-08 1999-08-04 K C L Enterprises Limited Product
BR0011858A (pt) 1999-06-25 2002-07-02 Arch Chem Inc Composição antimicrobiana
US6692757B1 (en) 1999-08-24 2004-02-17 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Multi-component, safe biocidal complex
CA2287150C (en) 1999-10-22 2006-12-05 Douglas W. Morck Method and apparatus for reducing outbreaks of diffuse lamellar keratitis
US20020066702A1 (en) 2000-02-22 2002-06-06 Jinfang Liu Antibacterial and antibiofilm bonded permanent magnets
JP2003532698A (ja) * 2000-05-10 2003-11-05 プリンストン ユニバーシティ 細菌の増殖および病理発生を調節するための化合物ならびに方法
JP2001340378A (ja) * 2000-05-30 2001-12-11 Ajinomoto Co Inc 医療または衛生用品
US8283135B2 (en) 2000-06-30 2012-10-09 The Procter & Gamble Company Oral care compositions containing combinations of anti-bacterial and host-response modulating agents
US7255881B2 (en) 2000-07-27 2007-08-14 Nucryst Pharmaceuticals Corp. Metal-containing materials
US7427416B2 (en) 2000-07-27 2008-09-23 Nucryst Pharmaceuticals Corp. Methods of treating conditions using metal-containing materials
US20040191329A1 (en) 2000-07-27 2004-09-30 Burrell Robert E. Compositions and methods of metal-containing materials
US20020123077A1 (en) * 2000-09-29 2002-09-05 O'toole George A. Novel compounds capable of modulating biofilms
WO2002027018A2 (en) 2000-09-29 2002-04-04 President And Fellows Of Harvard College Methods for identifying compounds that modulate biofilm activity
AU2002227247A1 (en) * 2000-12-08 2002-06-18 Brown, Dale G. Biofilm therapy process and elements
US7556807B2 (en) 2001-02-20 2009-07-07 Kane Biotech, Inc. Signal peptides, nucleic acid molecules and methods for treatment of caries
JP2002241546A (ja) 2001-02-22 2002-08-28 Toray Ind Inc 燃料取扱用部材
US6514483B2 (en) 2001-03-12 2003-02-04 Colgate Palmolive Company Strip for whitening tooth surfaces
WO2004092075A1 (en) 2001-04-09 2004-10-28 Bradley Downs Anti-biofilm forming structure and method of manufacturing the same
US7151139B2 (en) 2001-04-23 2006-12-19 Massachusetts Institute Of Technology Antimicrobial polymeric surfaces
CA2445591A1 (en) * 2001-04-27 2002-11-07 The Procter & Gamble Company Nitrogen heterocyclic compounds and compositions for controlling biofilms
US20030065292A1 (en) 2001-06-08 2003-04-03 Darouiche Rabih O. Ozonated medical devices and methods of using ozone to prevent complications from indwelling medical devices
JP2004532646A (ja) 2001-06-20 2004-10-28 ラバット・ブルウィング・カンパニイ・リミテッド 組み合わせ連続／バッチ発酵プロセス
US6592849B2 (en) 2001-06-21 2003-07-15 Colgate Palmolive Company Chewing gum to control malodorous breath
US6416744B1 (en) 2001-06-21 2002-07-09 Colgate Palmolive Company Tooth whitening chewing gum
EP1399198A1 (en) 2001-06-29 2004-03-24 The Procter & Gamble Company Absorbent article
WO2003004691A2 (en) 2001-07-06 2003-01-16 The General Hospital Corporation Regulators of biofilm formation and uses thereof
US20030134783A1 (en) 2001-07-31 2003-07-17 Harshey Rasika M. Use of cyclic heptapeptides for the inhibition of biofilm formation
US7052614B2 (en) 2001-08-06 2006-05-30 A.Y. Laboratories Ltd. Control of development of biofilms in industrial process water
US6696047B2 (en) 2001-09-13 2004-02-24 The Procter & Gamble Company Stable oral care compositions comprising chlorite
US20030099602A1 (en) 2001-10-25 2003-05-29 Levin Gilbert V. D-tagatose as an anti-biofilm agent
US7189351B2 (en) 2001-10-25 2007-03-13 Spherix Incorporated D-tagatose as an anti-biofilm agent
JP2003137758A (ja) 2001-10-29 2003-05-14 Kiyomitsu Kawasaki 頭髪化粧料用のマスキング組成物及び該マスキング組成物を含有する頭髪化粧料並びに頭髪化粧料のマスキング方法。
US20060177384A1 (en) 2001-12-04 2006-08-10 Brown Dale G Sialagogue coatings for interproximal devices
US20060034782A1 (en) 2001-12-04 2006-02-16 Brown Dale G Biofilm therapy interproximal devices
US7025986B2 (en) 2002-02-11 2006-04-11 International Tape Partners Llc Micromesh interproximal devices
US20060243297A1 (en) 2005-04-29 2006-11-02 Brown Dale G Coated monofilament oriented HDPE dental tapes
US6641739B2 (en) 2001-12-14 2003-11-04 Clearwater Systems, Llc Process of forming an oxidizing agent in liquid by use of ringing magnetic flux
US8329758B2 (en) 2002-02-05 2012-12-11 Gojo Industries, Inc. Skin sanitizing antimicrobial alcoholic compositions
US8685427B2 (en) 2002-07-31 2014-04-01 Boston Scientific Scimed, Inc. Controlled drug delivery
US8133501B2 (en) 2002-02-08 2012-03-13 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled drug delivery
US7993390B2 (en) 2002-02-08 2011-08-09 Boston Scientific Scimed, Inc. Implantable or insertable medical device resistant to microbial growth and biofilm formation
US6887270B2 (en) 2002-02-08 2005-05-03 Boston Scientific Scimed, Inc. Implantable or insertable medical device resistant to microbial growth and biofilm formation
AU2003230557A1 (en) 2002-02-22 2003-09-09 Ivigene Corporation In situ induced antigen technology (isiat) for identification of polynucleotides expressed during infection or colonization
US7338969B2 (en) * 2002-03-08 2008-03-04 Quonova, Llc Modulation of pathogenicity
US10577743B2 (en) 2002-04-09 2020-03-03 Gregory van Buskirk Laundry additive for providing antimicrobial effects to fabrics and interior surfaces of washing machine
AU2003225073A1 (en) 2002-04-18 2003-11-03 The University Of Iowa Research Foundation Methods of inhibiting and treating bacterial biofilms by metal chelators
US7201925B2 (en) 2002-04-23 2007-04-10 Nueryst Pharmaceuticals Corp. Treatment of ungual and subungual diseases
US7025950B2 (en) 2002-05-09 2006-04-11 The Procter & Gamble Company Oral care compositions comprising dicarboxy functionalized polyorganosiloxanes
JP2004018431A (ja) * 2002-06-14 2004-01-22 Kiyomitsu Kawasaki 口腔用香料組成物および該香料組成物を含有する口腔組成物
US8420699B1 (en) 2002-06-19 2013-04-16 Irvine L. Dubow Composition and methods of treatment using deionized and ozonated solution
CA2391641A1 (fr) 2002-06-28 2003-12-28 Robert Longin Plateforme robotisee de cultures cellulaires en batteries de reacteurs miniaturises, equipee d'un systeme de mesure en temps reel de la turbidite cellulaire ou toutes autres proprietes optiques
US8920826B2 (en) 2002-07-31 2014-12-30 Boston Scientific Scimed, Inc. Medical imaging reference devices
US6931688B2 (en) 2002-08-09 2005-08-23 Colgate-Palmolive Company Toothbrush
IL158509A (en) * 2003-10-20 2010-11-30 Biomor Israel Ltd Non-phytotoxic biocide composition containing tea tree oil and method for production thereof
US20100210745A1 (en) 2002-09-09 2010-08-19 Reactive Surfaces, Ltd. Molecular Healing of Polymeric Materials, Coatings, Plastics, Elastomers, Composites, Laminates, Adhesives, and Sealants by Active Enzymes
US20090238811A1 (en) 2002-09-09 2009-09-24 Mcdaniel C Steven Enzymatic Antimicrobial and Antifouling Coatings and Polymeric Materials
US20100233146A1 (en) 2002-09-09 2010-09-16 Reactive Surfaces, Ltd. Coatings and Surface Treatments Having Active Enzymes and Peptides
US20200299521A1 (en) 2002-09-09 2020-09-24 Reactive Surfaces, Ltd., Llp Peptide-containing antimicrobial coating compositions
US7452345B2 (en) 2002-09-17 2008-11-18 Baylor College Of Medicine Anti-infective endotracheal tube
CA2411508A1 (en) 2002-09-30 2004-03-30 Tony Romeo Methods for polysaccharide adhesin synthesis modulation
US20040110738A1 (en) 2002-10-22 2004-06-10 Gillis Scott H. Prophylactic treatment methods
FI116030B (fi) 2002-11-06 2005-09-15 Kemira Oyj Paperi- ja kartonkikoneiden termofiilisten mikrobien biofilminmuodostuksen esto
US8821862B2 (en) 2002-12-20 2014-09-02 Kane Biotech Inc. Soluble β-N-acetylglucosaminidase based antibiofilm compositions and uses thereof
US20040156884A1 (en) 2003-02-10 2004-08-12 Brown Dale G. Emulsion impregnated rawhide chews with antimicrobially active chlorhexidine
US7147888B2 (en) 2003-02-10 2006-12-12 Whitehill Oral Technologies, Inc. Emulsion impregnated rawhide chews
US20050064019A1 (en) 2003-02-10 2005-03-24 Hill Ira D. Impregnated, flexible, rawhide pet chews containing antimicrobially active chlorhexdine
US20050147719A1 (en) 2003-02-10 2005-07-07 Hill Ira D. Impregnated, flexible, rawhide pet chews containing ingestible, therapeutic ingredients
EP1601332A4 (en) 2003-03-07 2012-05-02 Verenium Corp HYDROLASES, NUCLEIC ACIDS ENCODING THEM, AND METHODS OF MAKING AND USING SAME
US8778889B2 (en) 2003-03-10 2014-07-15 The United States Of America As Represented By The Secretary Of The Army Antimicrobial decapeptide oral hygiene treatment
PL2204168T3 (pl) 2003-04-07 2015-06-30 Supernus Pharmaceuticals Inc Preparaty tetracyklin do jedorazowego dziennego podawania
US20050032093A1 (en) 2003-04-17 2005-02-10 Tony Romeo Novel genes involved in the escherichia coli biofilm formation and uses thereof
US20040265313A1 (en) 2003-04-23 2004-12-30 University Technologies International, Inc. Methods to regulate biofilm formation
US7087219B2 (en) * 2003-05-28 2006-08-08 Stanislaw R. Burzynski Toothpaste containing anticancer agents
CA2528522C (en) 2003-06-06 2016-07-12 Board Of Regents, The University Of Texas System Antimicrobial flush solutions
US20040254545A1 (en) 2003-06-16 2004-12-16 Rider Dean Loller Method and apparatus for extending feeding tube longevity
US20060162014A1 (en) 2003-07-07 2006-07-20 Jaffe Eileen K Alternate morpheeins of allosteric proteins as a target for the development of bioactive molecules
US8153410B2 (en) 2003-07-07 2012-04-10 Fox Chase Cancer Center Alternate morpheein forms of allosteric proteins as a target for the development of bioactive molecules
US8454566B2 (en) 2003-07-10 2013-06-04 Medtronic Minimed, Inc. Methods and compositions for the inhibition of biofilms on medical devices
WO2005030186A2 (en) 2003-07-28 2005-04-07 Univ Maryland Method for attenuating virulence of microbial pathogens and for inhibiting microbial biofilm formation
US7314857B2 (en) 2003-08-25 2008-01-01 Kane Biotech Inc. Synergistic antimicrobial compositions and methods of inhibiting biofilm formation
EP1667619A4 (en) 2003-09-19 2007-10-10 Drugtech Corp PHARMACEUTICAL FEEDING SYSTEM
US20060224103A1 (en) 2003-10-03 2006-10-05 Michael Rontal Method and apparatus for the ultrasonic cleaning of biofilm coated surfaces
SG120954A1 (en) * 2003-10-10 2006-04-26 Agency For Science Technologya Inhibitors of yeast filamentous growth and method of their manufacture
FI117056B (fi) 2003-11-06 2006-05-31 Kemira Oyj Menetelmä biofilmiä muodostavien mikro-organismien esiintymisen monitoroimiseksi paperiteollisuudessa
US9539367B2 (en) 2003-12-04 2017-01-10 University Of Iowa Research Foundation Gallium inhibits biofilm formation
US7504123B2 (en) 2004-01-09 2009-03-17 Ecolab Inc. Methods for washing poultry during processing with medium chain peroxycarboxylic acid compositions
US7887641B2 (en) 2004-01-09 2011-02-15 Ecolab Usa Inc. Neutral or alkaline medium chain peroxycarboxylic acid compositions and methods employing them
US8999175B2 (en) 2004-01-09 2015-04-07 Ecolab Usa Inc. Methods for washing and processing fruits, vegetables, and other produce with medium chain peroxycarboxylic acid compositions
US20050161636A1 (en) 2004-01-09 2005-07-28 Ecolab Inc. Methods for washing and processing fruits, vegetables, and other produce with medium chain peroxycarboxylic acid compositions
US7744555B2 (en) 2004-02-06 2010-06-29 Depuy Spine, Inc. Implant having a photocatalytic unit
US8267883B2 (en) 2004-02-06 2012-09-18 Depuy Spine, Inc. Photocatalytic implant having a sensor
US20050260181A1 (en) 2004-03-05 2005-11-24 Immunopath Profile, Inc. Compositions and methods for tissue repair
US8076117B2 (en) 2004-03-18 2011-12-13 Mayo Foundation For Medical Education And Research Microbial biofilm removal methods and systems
ES2245875B1 (es) 2004-03-26 2006-11-16 Joaquin Espuelas Peñalva Proceso de fabricacion y filtro de tejido no tejido y/o de laminas o estructuras inyectadas filtrantes obtenidos por dicho proceso para la filtracion y eliminacion de la legionella pneumofila.
US7144992B2 (en) 2004-04-01 2006-12-05 Kane Biotech Inc. Synergistic antimicrobial compositions and methods for reducing biofilm formation
WO2005109960A2 (en) 2004-04-30 2005-11-17 Bruno Cynthia K Antagonistic properties of reef fish microflora
US7217425B2 (en) 2004-07-23 2007-05-15 Depuy Spine, Inc. Autologous coatings for implants
US8715733B2 (en) 2004-07-23 2014-05-06 DePuy Synthes Products, LLC Enhanced adipose tissue
US7399742B2 (en) 2004-07-23 2008-07-15 Depuy Spine, Inc. Anti-osteolytic therapy involving adiponectin
CN101010003B (zh) 2004-07-30 2012-07-04 金佰利-克拉克国际公司 抗微生物的银组合物
JP2006062966A (ja) 2004-08-24 2006-03-09 Teiwa Engineering:Kk Ｄｎａ合成酵素阻害組成物、ｄｎａトポイソメラーゼ阻害組成物、テロメラーゼ阻害組成物、癌細胞増殖抑制組成物および抗炎症組成物
WO2006031699A2 (en) 2004-09-10 2006-03-23 Diversa Corporation Compositions and methods for making and modifying oils
US7612045B2 (en) 2004-09-14 2009-11-03 Sequoia Sciences, Inc. Compounds, compositions and methods for controlling biofilms and bacterial infections
US7691418B2 (en) 2004-09-17 2010-04-06 Oystershell Nv Composition for inhibiting or preventing the formation of a biofilm
US7795000B2 (en) 2004-09-24 2010-09-14 Ecolab Inc. Foaming composition of competitive exclusion microbes and methods of using same
PT1791791T (pt) 2004-09-27 2019-09-12 Special Water Patents B V Métodos e composições para tratamento de água
US9801982B2 (en) 2004-09-28 2017-10-31 Atrium Medical Corporation Implantable barrier device
US20060110456A1 (en) 2004-11-03 2006-05-25 National University Of Singapore Method for biocidal and/or biostatic treatment and compositions therefor
US7297327B2 (en) 2004-12-21 2007-11-20 Colgate-Palmolive Company Oral care malodor composition
EP1841873A2 (fr) 2004-12-29 2007-10-10 Centre de Biotechnologie de Sfax - CBS Une l-arabinose isomerase ayant une dependance minime en ions metalliques pour son activite et sa thermostabilite, sa sequence nucleotidique isolee et caracterisee
EP1846496A2 (en) 2005-02-07 2007-10-24 E.I. Dupont De Nemours And Company Chitosan-base antimicrobial thermoplastic polymer blends
US20100136112A1 (en) 2005-06-15 2010-06-03 Martin Roy W Oxidizing composition including a gel layer
US20100183693A1 (en) 2005-03-01 2010-07-22 Martin Roy W Slow dissolving tablet composition for the in-situ generation of chlorine dioxide for use in a multi-tablet dispenser
US7534368B2 (en) 2005-03-01 2009-05-19 Truox, Inc. Oxidizing composition including a gel layer
US20090297495A1 (en) 2005-03-08 2009-12-03 Verenium Corporation Hydrolases, nucleic acids encoding them and methods for improving paper strength
US10918618B2 (en) 2005-03-10 2021-02-16 3M Innovative Properties Company Methods of reducing microbial contamination
EP1858506A2 (en) 2005-03-10 2007-11-28 3M Innovative Properties Company Methods of treating ear infections
WO2006100154A1 (en) 2005-03-24 2006-09-28 Nolabs Ab Cosmetic treatment with nitric oxide, device for performing said treatment and manufacturing method therefor
CA2603235A1 (en) 2005-03-28 2006-10-05 Bioresponse, Llc Diindolylmethane-based compositions and methods of use thereof for promoting oral mucosal and bone health
US20070009566A1 (en) 2005-04-04 2007-01-11 Naomi Balaban Method and apparatus for treating bacterial infections in devices
FR2885130B1 (fr) 2005-04-28 2007-06-29 Centre Nat Rech Scient Procede de preparation de polylysines dendrimeres greffes
US7838532B2 (en) 2005-05-18 2010-11-23 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8546423B2 (en) 2005-05-18 2013-10-01 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
CN101184522B (zh) 2005-05-18 2011-12-21 尼克塔治疗公司 用于支气管内治疗的阀、设备和方法
US20100158967A1 (en) 2005-05-24 2010-06-24 Ted Reid Selenium-based biocidal formulations and methods of use thereof
US20100158966A1 (en) 2005-05-24 2010-06-24 Ted Reid Selenium-based biocidal formulations and methods of use thereof
US9370187B2 (en) 2005-05-24 2016-06-21 Selenium, Ltd. Selenium-based biocidal formulations and methods of use thereof
CA2606565C (en) 2005-05-27 2016-05-10 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
AU2006265707B2 (en) 2005-07-01 2012-06-14 Kane Biotech Inc. Antimicrobial compositions for inhibiting growth and proliferation of a microbial biofilm on medical devices
US20080206276A1 (en) 2005-07-08 2008-08-28 Michael Otto Targeting Poly-Gamma-Glutamic Acid to Treat Staphylococcus Epidermidis and Related Infections
AU2006202432B2 (en) 2005-07-11 2012-05-17 Covidien Lp Antimicrobial sutures and methods of making them
US20070014739A1 (en) * 2005-07-14 2007-01-18 Eldridge Gary R Compositions and methods for controlling biofilms and bacterial infections
US20080318268A1 (en) 2005-07-22 2008-12-25 Merle E Olson Devices and Methods for the Selection of Agents with Efficacy Against Biofilm
US20070062884A1 (en) 2005-08-11 2007-03-22 Board Of Regents, The University Of Texas System N-halamines compounds as multifunctional additives
WO2007024876A2 (en) 2005-08-24 2007-03-01 The Board Of Trustees Of Leland Stanford Junior University Methods for treating and monitoring inflammation and redox imbalance in cystic fibrosis
US20090192227A1 (en) 2005-08-24 2009-07-30 Rabindra Tirouvanziam N-Acetylcysteine Compositions and Methods for Treating Acute Exacerbations of Inflammatory Lung Disease
FI118735B (fi) 2005-09-13 2008-02-29 Kemira Oyj Menetelmä peroksihappojen valmistamiseksi
US7264005B2 (en) 2005-09-23 2007-09-04 Wong Thomas K Toothpick device
US8574627B2 (en) 2006-11-06 2013-11-05 Atrium Medical Corporation Coated surgical mesh
US20070083156A1 (en) 2005-10-06 2007-04-12 Atrium Medical Corporation Subcutaneous needle connection system
US7794698B2 (en) 2005-11-02 2010-09-14 Oplon B.V. Composition and methods for cell killing
US8697102B2 (en) 2005-11-02 2014-04-15 Oplon B.V. Compositions and methods for cell killing
US7450228B2 (en) 2005-11-09 2008-11-11 Chemimage Corporation Spectral imaging of biofilms
ES2526640T3 (es) 2005-11-18 2015-01-14 Glanbia Nutritionals (Ireland) Limited Composiciones para romper e inhibir la reconstitución de la biopelícula de heridas
DK2341140T3 (da) 2005-12-01 2017-11-06 Nuevolution As Fremgangsmåde til enzymatisk kodning ved effektiv syntese af store biblioteker
RU2396941C2 (ru) 2005-12-02 2010-08-20 Джи Ай Си ИННОВАТИОНЗ КОМПАНИ Наполнители с экстрактом коры магнолии для ухода за полостью рта
US20070207095A1 (en) * 2005-12-09 2007-09-06 Research Foundation Of State University Of New York Induction of a physiological dispersion response in bacterial cells in a biofilm
EP1973587B1 (en) 2005-12-12 2019-02-06 AllAccem, Inc. Methods and systems for preparing antimicrobial films and coatings
PT1962873E (pt) 2005-12-14 2013-08-29 Oxthera Inc Composições farmacêuticas compreendendo bactérias redutoras de oxalato
JP5246833B2 (ja) 2005-12-16 2013-07-24 独立行政法人産業技術総合研究所 アディポネクチン産生増強剤
US20070140990A1 (en) 2005-12-21 2007-06-21 Nataly Fetissova Oral Compositions Comprising Propolis
US20090253613A1 (en) 2006-01-04 2009-10-08 Do-Coop Technologies Ltd. Solid-Fluid Composition
US9532943B2 (en) 2010-12-20 2017-01-03 Cormatrix Cardiovascular, Inc. Drug eluting patch for the treatment of localized tissue disease or defect
AU2007208169A1 (en) 2006-01-30 2007-08-02 Lawrence R. Bernstein Use of gallium to treat biofilm-associated infectons
WO2007092314A2 (en) 2006-02-02 2007-08-16 Verenium Corporation Esterases and related nucleic acids and methods
JP2009531287A (ja) 2006-02-07 2009-09-03 ホワイトヒル・オーラル・テクノロジーズ・インコーポレイテツド 唾液分泌促進薬に基づく口腔ケア製品
MX2008010359A (es) 2006-02-09 2009-01-30 Elevance Renewable Sciences Composiciones, metodos y sistemas antimicrobianos.
JP2007239280A (ja) 2006-03-08 2007-09-20 Mitsuba Corp 車両用開閉体の制御装置
US9649513B2 (en) 2006-03-24 2017-05-16 Colgate—Palmolive Company Aerosol dispenser
US8486428B2 (en) 2006-03-27 2013-07-16 Board Of Regents, The University Of Texas System Compositions and methods for making and using acyclic N-halamine-based biocidal polymeric materials and articles
US7781166B2 (en) 2006-03-31 2010-08-24 Marshall University Research Corporation Methods of detecting and controlling mucoid pseudomonas biofilm production
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
US20120219638A1 (en) 2006-06-22 2012-08-30 Olson Merle E Method and Compositions for Treating Plant Infections
US20100129466A1 (en) 2006-06-22 2010-05-27 Inovotech, Inc. Compositions and methods for treating plants
US20080044491A1 (en) 2006-06-30 2008-02-21 Nucryst Pharmaceuticals Metal-containing formulations and methods of use
EP1872791A1 (en) 2006-06-30 2008-01-02 Institut Pasteur Use of bacterial polysaccharides for biofilm inhibition
US20080107707A1 (en) 2006-07-06 2008-05-08 Regents Of The University Of Colorado Polymerizable antimicrobial composition
EP2040550A2 (en) 2006-07-14 2009-04-01 Ciba Holding Inc. Polysiloxane antimicrobials
JP2009544807A (ja) 2006-07-25 2009-12-17 フジフィルム ハント スマート サーフェイシーズ，エルエルシー ポリシロキサンベースのｉｎｓｉｔｕポリマー混合物−組成物、物品およびその調整方法
BRPI0714876B1 (pt) 2006-08-04 2022-04-19 Verenium Corporation Ácido nucleico isolado, sintético ou recombinante, cassete de expressão, vetor ou veículo de clonagem, célula bacteriana, fúngica ou de levedura transformada, polipeptídeo isolado, sintético ou recombinante, composição, bem como métodos de produção e de usos dos mesmos
US8680148B2 (en) 2006-08-11 2014-03-25 University Of Washington Metallo-desferrioxamine complexes and their use in the treatment of bacterial infections
US7923425B2 (en) 2006-08-21 2011-04-12 Henkel Ag & Co. Kgaa Low-foaming, acidic low-temperature cleaner and process for cleaning surfaces
AU2007290494A1 (en) 2006-08-30 2008-03-06 Southeastern Medical Technologies Methods, compositions and apparatuses to treat wounds with pressures altered from atmospheric
WO2008029401A1 (en) 2006-09-05 2008-03-13 Hanoch Kislev Nucleation in liquid, methods of use thereof and methods of generation thereof
US8021610B2 (en) 2006-09-07 2011-09-20 Biolargo Life Technologies, Inc. Systems providing antimicrobial activity to an environment
DE102006046922B3 (de) 2006-09-27 2007-11-15 Julius-Maximilians-Universität Würzburg Biofilm-hemmende Wirkung sowie anti-infektive Aktivität N,C-verknüpfter Arylisochinoline, deren pharmazeutischen Zusammensetzung und deren Verwendung
US20110008402A1 (en) 2006-10-13 2011-01-13 Kane Biotech Inc. Souluble b-n-acetylglucoseaminidase based antibiofilm compositions and uses thereof
US9492596B2 (en) 2006-11-06 2016-11-15 Atrium Medical Corporation Barrier layer with underlying medical device and one or more reinforcing support structures
EP2084234A2 (en) 2006-11-08 2009-08-05 Massachusetts Institute of Technology Polymeric coatings that inactivate viruses and bacteria
DE102007039652A1 (de) 2006-12-05 2008-06-12 Henkel Kgaa Mittel zur Behandlung harter Oberflächen
US7906544B2 (en) 2007-01-26 2011-03-15 North Carolina State University Inhibition of bacterial biofilms with imidazole derivatives
CN104212822A (zh) 2007-01-30 2014-12-17 Bp法人北美有限公司 用于处理木质纤维素的酶、编码它们的核酸及其制备和应用方法
US8257749B2 (en) 2007-02-08 2012-09-04 Biolargo Life Technologies, Incorporated Systems providing at least pesticidal activity
KR20100014954A (ko) 2007-03-09 2010-02-11 다니스코 유에스 인크. 호알칼리성 바실러스 종 α-아밀라아제 변이체, α-아밀라아제 변이체를 함유하는 조성물 및 사용 방법
CA2681621A1 (en) 2007-03-23 2008-10-02 Danisco Us Inc. Enhanced amylase production by n-terminal addition to mature amylase protein
US8211361B2 (en) 2007-03-26 2012-07-03 Board Of Regents, The University Of Texas System N-halamine-based rechargeable biofilm-controlling tubular devices, method of making and using
TW200901890A (en) 2007-04-03 2009-01-16 Sure Internat Ventures B V New compostions and methods for cell killing
US20080253976A1 (en) 2007-04-16 2008-10-16 Douglas Craig Scott Personal Care Compositions Comprising An Antimicrobial Blend of Essential Oils or Constituents Thereof
FR2915386B1 (fr) 2007-04-24 2009-08-21 Pierre Fabre Medicament Sa Utilisation d'un extrait aqueux de pepins de raisin en association avec au moins un sel de fluor contre la formation ou l'accumulation du biofilm dentaire et les compositions comprenant cette association
EP2166862A2 (en) 2007-05-01 2010-03-31 Oplon B.V. Compositions and methods for cell killing
WO2008132717A2 (en) 2007-05-01 2008-11-06 Sure International Ventures B.V. Compositions and methods for cell killing
WO2009014781A2 (en) 2007-05-02 2009-01-29 Nucryst Pharmaceuticals Corp. Metal-containing materials for treatment of bacterial conditions
AU2008248118A1 (en) 2007-05-03 2008-11-13 Northeastern University Methods of treating fungal infections
US20100196455A1 (en) 2007-05-04 2010-08-05 Transave, Inc. Compositions of Multicationic Drugs for Reducing Interactions with Polyanionic Biomolecules and Methods of Use Thereof
US8569449B2 (en) 2007-05-08 2013-10-29 University Of Louisville Research Foundation, Inc. Synthetic peptides and peptide mimetics
GB2463181B (en) 2007-05-14 2013-03-27 Univ New York State Res Found Induction of a physiological dispersion response in bacterial cells in a biofilm
US9393261B2 (en) 2011-07-22 2016-07-19 Body Glide LLC Antimicrobial anti-chafing chelated silver oxide compound
EP1994930A1 (en) 2007-05-22 2008-11-26 Novartis AG Triazol compounds for treating biofilm formation
RU2009149406A (ru) 2007-05-30 2011-07-10 ДАНИСКО ЮЭс, ИНК., ДЖЕНЕНКОР ДИВИЖН (US) Варианты альфа-амилазы с повышенными уровнями продукции в процессах ферментации
MX2009012682A (es) 2007-05-30 2009-12-14 Danisco Us Inc Genencor Div Variantes mejoradas de la alfa-amilasa de bacillus licheniformis.
KR20100054779A (ko) 2007-06-07 2010-05-25 인노보테크, 인크. 종자 발아를 증가시키기 위한 방법 및 이를 위한 고원자가 은을 포함한 조성물
WO2008157350A2 (en) 2007-06-14 2008-12-24 Mayo Foundation For Medical Education And Research Methods and materials for reducing biofilms
KR20100061441A (ko) 2007-07-06 2010-06-07 래크리드 인코포레이티드 기도 내 생물막을 용해시키기 위한 가수분해 및 산화효소의 용도
US8926951B2 (en) 2007-07-09 2015-01-06 Micropure, Inc. Composition for preventing oral disease by penetrating polymicrobial oral biofilms and killing oral pathogens
WO2009009065A1 (en) 2007-07-09 2009-01-15 The Trustees Of The University Of Pennsylvania Biofilm prevention using lactoferrin
EP2176420B1 (en) 2007-07-13 2018-02-14 University of Pittsburgh - Of the Commonwealth System of Higher Education Virus derived antimicrobial peptides
US8702640B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc System, devices, and methods including catheters configured to monitor and inhibit biofilm formation
US9005263B2 (en) 2007-08-17 2015-04-14 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable sterilizing excitation delivery implants
US8647292B2 (en) 2007-08-17 2014-02-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between two or more wettability states
US8753304B2 (en) 2007-08-17 2014-06-17 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having acoustically actuatable waveguide components for delivering a sterilizing stimulus to a region proximate a surface of the catheter
US20090163964A1 (en) 2007-08-17 2009-06-25 Searete Llc, A Limited Liability Corporation Of The State Of Delaware System, devices, and methods including sterilizing excitation delivery implants with general controllers and onboard power
US8734718B2 (en) 2007-08-17 2014-05-27 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having an actively controllable therapeutic agent delivery component
US20090163977A1 (en) 2007-08-17 2009-06-25 Searete Llc, A Limited Liability Corporation Of The State Of Delaware System, devices, and methods including sterilizing excitation delivery implants with cryptographic logic components
US8366652B2 (en) 2007-08-17 2013-02-05 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US20090048648A1 (en) 2007-08-17 2009-02-19 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Self-sterilizing device
US8706211B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having self-cleaning surfaces
US20090177254A1 (en) 2007-08-17 2009-07-09 Searete Llc, A Limited Liability Of The State Of The State Of Delaware System, devices, and methods including actively-controllable electrostatic and electromagnetic sterilizing excitation delivery system
US8460229B2 (en) 2007-08-17 2013-06-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between transmissive and reflective states
US8162924B2 (en) 2007-08-17 2012-04-24 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable superoxide water generating systems
US20110160644A1 (en) 2007-08-17 2011-06-30 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems, devices, and methods including catheters configured to release ultraviolet energy absorbing agents
KR20100063064A (ko) 2007-08-20 2010-06-10 두-쿱 테크놀로지스 리미티드 부화된 나노구조 조성물
WO2009035553A2 (en) 2007-09-11 2009-03-19 University Of Tennessee Research Foundation Analogs of tetramic acid
US9150788B2 (en) 2007-09-18 2015-10-06 Syracuse University Non-amphiphile-based water-in-water emulsion and uses thereof
KR20100074199A (ko) 2007-09-19 2010-07-01 보드 오브 리전츠 더 유니버시티 오브 텍사스 시스템 착색제계 ｎ－할라민 조성물 및 제조 및 사용 방법
KR20140068239A (ko) 2007-09-20 2014-06-05 텔 하쇼머 메디컬 리서치 인프라스트럭쳐 앤드 서비시스 리미티드． 세포 유착을 방지하기 위한 수생 기원의 조성물 및 그것의 사용 방법
US20090112186A1 (en) 2007-10-02 2009-04-30 Adams Mark L Catheter assembly with increased torsional stiffness
US8604004B2 (en) 2007-10-04 2013-12-10 President And Fellows Of Harvard College Moenomycin analogs, methods of synthesis, and uses thereof
CA2702811A1 (en) 2007-10-25 2009-04-30 Innovotech Inc. Natural photodynamic agents and their use
US20090148342A1 (en) 2007-10-29 2009-06-11 Bromberg Steven E Hypochlorite Technology
US8980299B2 (en) 2007-10-31 2015-03-17 Cordis Corporation Method of making a vascular closure device
NZ584366A (en) 2007-11-05 2012-03-30 Danisco Us Inc Variants of bacillus licheniformis alpha-amylase with increased thermostability and/or decreased calcium dependence
NZ584434A (en) 2007-11-05 2011-12-22 Danisco Us Inc VARIANTS OF BACILLUS sp. TS-23 ALPHA-AMYLASE WITH ALTERED PROPERTIES
EP2209856B1 (en) 2007-11-12 2019-07-10 Aerogel ApS Aerogel compositions
US8227017B2 (en) 2007-11-13 2012-07-24 Quick-Med Technologies, Inc. System and method for enhancing the efficacy of antimicrobial contact lenses and other surfaces
DE102008052451A1 (de) 2007-11-14 2009-05-20 Luk Lamellen Und Kupplungsbau Beteiligungs Kg Drehmomentwandler mit Überbrückungskupplung, die einen geteilten Kolben aufweist
FR2924025B1 (fr) 2007-11-27 2011-05-13 Rc Lux Dispositif de securisation de liquide par rayonnements ultraviolets au point d'utilisation et procede de securisation de liquide
WO2009070304A1 (en) 2007-11-27 2009-06-04 North Carolina State University Inhibition of biofilms in plants with imidazole derivatives
WO2009068841A2 (en) 2007-11-27 2009-06-04 Algipharma Ipr As Use of alginate oligomers in combating biofilms
PL2529723T3 (pl) 2007-11-30 2016-09-30 Kompozycje i sposoby leczenia zakażeń pochwy i chorobotwórczych biofilmów pochwy
US8153119B2 (en) 2007-12-18 2012-04-10 Trustees Of Boston University Engineered enzymatically active bacteriophage and methods for dispersing biofilms
JP2011518543A (ja) 2008-01-10 2011-06-30 トラスティーズ オブ ボストン ユニバーシティ 抗微生物剤のための佐剤としての改変バクテリオファージならびにその組成物および使用方法
KR20100109945A (ko) 2008-02-04 2010-10-11 다니스코 유에스 인크. 변경된 특성을 지닌 ｔｓ23 알파-아밀라아제 변이체
EP2249786B1 (en) 2008-02-08 2017-07-19 Colgate-Palmolive Company Oral care product and methods of use and manufacture thereof
PL2254591T3 (pl) 2008-02-08 2018-01-31 Prothera Inc Inhibicja i leczenie biofilmów żołądkowo-jelitowych
WO2009108716A2 (en) 2008-02-27 2009-09-03 University Of Louisville Research Foundation Synthetic peptides
EP2283130B1 (en) 2008-04-03 2014-09-10 Kane Biotech Inc. Dispersin B(TM), 5-fluorouracil, deoxyribonuclease I and proteinase K-based antibiofilm compositions and uses thereof
WO2009123575A1 (en) 2008-04-04 2009-10-08 National University Of Singapore A photosensitising composition and its uses
US9005643B2 (en) 2008-04-04 2015-04-14 North Carolina State University Inhibition of bacterial biofilms with imidazole-phenyl derivatives
EP2278989B1 (en) 2008-04-08 2021-05-26 Melinta Therapeutics, Inc. Oritavancin for inhibiting and treating biofilms
US8567612B2 (en) 2008-04-15 2013-10-29 Nanoh2O, Inc. Hybrid TFC RO membranes with nitrogen additives
WO2009131654A2 (en) 2008-04-21 2009-10-29 North Carolina State University Inhibition and dispersion of bacterial biofilms with imidazole-triazole derivatives
WO2009132043A1 (en) 2008-04-22 2009-10-29 Abnousi, Freddy Endotracheal tube
US20100015245A1 (en) 2008-04-24 2010-01-21 Joe Harrison Combination of Copper Cations with Peroxides or Quaternary Ammonium Compounds for the Treatment of Biofilms
EP2296476A4 (en) 2008-05-19 2013-11-06 Microbiotix Inc HEMMER OF BACTERIAL BIOFILMATION
AU2009254152A1 (en) 2008-06-02 2009-12-10 Spiderbiotech S.R.L. Antibacterial peptides
US8591961B2 (en) 2008-09-04 2013-11-26 Allergan, Inc. Aesthetic treatment of scars and aging skin
US8398705B2 (en) 2008-06-11 2013-03-19 Eric Mangiardi Stent
US10022164B2 (en) 2008-06-11 2018-07-17 Eventions, Llc Orthopedic fastener device
US8246691B2 (en) 2008-06-11 2012-08-21 Eric Mangiardi Stent
WO2009154988A2 (en) 2008-06-17 2009-12-23 University Of Iowa Research Foundation Agr-mediated inhibition and dispersal of biofilms
US20090324820A1 (en) 2008-06-30 2009-12-31 Chartier Douglas M Systems, Methods, and Compositions for the Inhibition of Corrosion of Metallic Surfaces
US20100059433A1 (en) 2008-07-10 2010-03-11 Board Of Regents, The University Of Texas System Polymer deposition and modification of membranes for fouling resistance
AU2009277252B2 (en) 2008-07-30 2014-01-16 Mesynthes Limited Tissue scaffolds derived from forestomach extracellular matrix
WO2010017243A1 (en) 2008-08-04 2010-02-11 Kai Bioenergy Continuous cultivation, harvesting, and oil extraction of photosynthetic cultures
AU2009282691A1 (en) 2008-08-21 2010-02-25 Tpk Holding Co., Ltd. Enhanced surfaces, coatings, and related methods
US8945142B2 (en) 2008-08-27 2015-02-03 Cook Medical Technologies Llc Delivery system for implanting nasal ventilation tube
EP2335073A4 (en) 2008-09-02 2012-09-26 Univ Maryland IN VIVO DIAGNOSIS AND TREATMENT OF BIOFILM INFECTIONS
EP2349372A4 (en) 2008-09-19 2013-10-09 Univ Pennsylvania SOLDER FORMULATION AND USE THEREOF IN TISSUE WELDING
CN104892728A (zh) 2008-09-24 2015-09-09 特尔哈肖梅尔医学研究基础设施和服务有限公司 用于防止细胞粘附的肽和组合物及其使用方法
WO2010039563A2 (en) 2008-09-30 2010-04-08 University Of Maryland, Baltimore Protective vaccine against staphylococcus aureus biofilms comprising cell wall-associated immunogens
GB0818074D0 (en) 2008-10-02 2008-11-05 Lytix Biopharma As Treatment of biofilms
GB0818072D0 (en) 2008-10-02 2008-11-05 Lytix Biopharma As Compounds
US20140370078A1 (en) 2013-06-12 2014-12-18 The Board Of Trustees Of The Leland Stanford Junior University Topical and Transdermal Delivery of HIF-1 Modulators to Prevent and Treat Chronic Wounds
US10098857B2 (en) 2008-10-10 2018-10-16 The Board Of Trustees Of The Leland Stanford Junior University Topical and transdermal delivery of HIF-1 modulators to prevent and treat chronic wounds
US20100099599A1 (en) 2008-10-16 2010-04-22 Advanced Biocatalytics Corporation Enhanced performance hydrogen peroxide formulations comprising proteins and surfactants
MX2011004265A (es) 2008-10-24 2011-06-02 Destiny Pharma Ltd Usos novedosos de compuestos de porfirina.
US9060934B2 (en) 2008-10-31 2015-06-23 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8551505B2 (en) 2008-10-31 2013-10-08 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8545806B2 (en) 2008-10-31 2013-10-01 The Invention Science Fund I, Llc Compositions and methods for biological remodeling with frozen particle compositions
US9072799B2 (en) 2008-10-31 2015-07-07 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8409376B2 (en) 2008-10-31 2013-04-02 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8731840B2 (en) 2008-10-31 2014-05-20 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8731841B2 (en) 2008-10-31 2014-05-20 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8551506B2 (en) 2008-10-31 2013-10-08 The Invention Science Fund I, Llc Compositions and methods for administering compartmentalized frozen particles
US9060926B2 (en) 2008-10-31 2015-06-23 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US9050317B2 (en) 2008-10-31 2015-06-09 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US9050070B2 (en) 2008-10-31 2015-06-09 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US20100111841A1 (en) 2008-10-31 2010-05-06 Searete Llc Compositions and methods for surface abrasion with frozen particles
US20100111835A1 (en) 2008-10-31 2010-05-06 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Compositions and methods for therapeutic delivery with frozen particles
US8762067B2 (en) 2008-10-31 2014-06-24 The Invention Science Fund I, Llc Methods and systems for ablation or abrasion with frozen particles and comparing tissue surface ablation or abrasion data to clinical outcome data
US8793075B2 (en) 2008-10-31 2014-07-29 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8788211B2 (en) 2008-10-31 2014-07-22 The Invention Science Fund I, Llc Method and system for comparing tissue ablation or abrasion data to data related to administration of a frozen particle composition
US8603495B2 (en) 2008-10-31 2013-12-10 The Invention Science Fund I, Llc Compositions and methods for biological remodeling with frozen particle compositions
US9060931B2 (en) 2008-10-31 2015-06-23 The Invention Science Fund I, Llc Compositions and methods for delivery of frozen particle adhesives
US20100111831A1 (en) 2008-10-31 2010-05-06 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Compositions and methods for surface abrasion with frozen particles
US8545855B2 (en) 2008-10-31 2013-10-01 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US20100111857A1 (en) 2008-10-31 2010-05-06 Boyden Edward S Compositions and methods for surface abrasion with frozen particles
US8545857B2 (en) 2008-10-31 2013-10-01 The Invention Science Fund I, Llc Compositions and methods for administering compartmentalized frozen particles
US20100111836A1 (en) 2008-10-31 2010-05-06 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Compositions and methods for therapeutic delivery with frozen particles
US9072688B2 (en) 2008-10-31 2015-07-07 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US9050251B2 (en) 2008-10-31 2015-06-09 The Invention Science Fund I, Llc Compositions and methods for delivery of frozen particle adhesives
US8721583B2 (en) 2008-10-31 2014-05-13 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US20100111834A1 (en) 2008-10-31 2010-05-06 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Compositions and methods for therapeutic delivery with frozen particles
US8849441B2 (en) 2008-10-31 2014-09-30 The Invention Science Fund I, Llc Systems, devices, and methods for making or administering frozen particles
US8725420B2 (en) 2008-10-31 2014-05-13 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8784384B2 (en) 2008-10-31 2014-07-22 The Invention Science Fund I, Llc Frozen compositions and array devices thereof
JP5647137B2 (ja) 2008-11-07 2014-12-24 エージェンシー フォー サイエンス，テクノロジー アンド リサーチ 新規のポリアミノポリケチド抗生物質およびその使用
TW201029966A (en) 2008-11-17 2010-08-16 Bayer Materialscience Llc Biofilm-inhibitory coatings that release salicylic acid by hydrolisis
EP2365969B1 (en) 2008-11-20 2017-03-22 Yissum Research Development Company of The Hebrew University of Jerusalem Ltd. Novel anti-biofilm agents
US20110295090A1 (en) 2008-12-04 2011-12-01 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems, devices, and methods including implantable devices with anti-microbial properties
US8585627B2 (en) 2008-12-04 2013-11-19 The Invention Science Fund I, Llc Systems, devices, and methods including catheters configured to monitor biofilm formation having biofilm spectral information configured as a data structure
US20120010481A1 (en) 2008-12-04 2012-01-12 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems, devices, and methods including implantable devices with anti-microbial properties
US20110208026A1 (en) 2008-12-04 2011-08-25 Goodall Eleanor V Systems, devices, and methods including implantable devices with anti-microbial properties
US20110208021A1 (en) 2008-12-04 2011-08-25 Goodall Eleanor V Systems, devices, and methods including implantable devices with anti-microbial properties
US20110208023A1 (en) 2008-12-04 2011-08-25 Goodall Eleanor V Systems, devices, and methods including implantable devices with anti-microbial properties
US20120209090A1 (en) 2011-02-14 2012-08-16 Searete Llc, A Limited Liability Corporation Of The Sate Of Delaware Systems, devices, and methods including implantable devices with anti-microbial properties
US20110152751A1 (en) 2008-12-04 2011-06-23 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems, devices, and methods including catheters having UV-Energy emitting coatings
US20110160681A1 (en) 2008-12-04 2011-06-30 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems, devices, and methods including catheters having light removable coatings based on a sensed condition
US20110294668A1 (en) 2008-12-08 2011-12-01 North Carolina State University Inhibition and dispersion of biofilms in plants with imidazole-triazole derivatives
EP2384335A1 (en) 2008-12-10 2011-11-09 Pan-Eco S.A. Biosurfactant composition produced by a new bacillus licheniformis strain, uses and products thereof
WO2010077985A1 (en) 2008-12-16 2010-07-08 Board Of Regents, The University Of Texas System In situ formation of nanoparticles in resins
GB0823265D0 (en) 2008-12-20 2009-01-28 Convatec Technologies Inc Antimicrobial Composition
US8440631B2 (en) 2008-12-22 2013-05-14 Aegis Therapeutics, Llc Compositions for drug administration
KR101383408B1 (ko) 2008-12-29 2014-04-17 텔 하쇼머 메디컬 리서치 인프라스트럭쳐 앤드 서비시스 리미티드． 세포 유착 방지를 위한 펩티드와 조성물 및 그것의 사용 방법
US8658225B2 (en) 2008-12-31 2014-02-25 Znova, Llc Herbal-based nasal solution and method of use thereof
WO2010080836A2 (en) 2009-01-06 2010-07-15 C3 Jian, Inc. Antibacterial and antifungal peptides
US8778370B2 (en) 2009-01-16 2014-07-15 Sterilex Corporation Method and composition for inhibiting growth of microorganisms in industrial process waters in the presence of anionic anti-fouling additives
US9622481B2 (en) 2009-01-23 2017-04-18 Kane Biotech Inc. Biofilm-removing antimicrobial compositions and uses thereof
WO2010083589A1 (en) 2009-01-23 2010-07-29 Kane Biotech Inc. Biofilm-removing antimicrobial compositions and uses thereof
US20200138033A1 (en) 2009-02-03 2020-05-07 Microbion Corporation Bismuth-thiols as antiseptics for agricultural, industrial and other uses
EP3695835A1 (en) 2009-02-03 2020-08-19 Microbion Corporation Bismuth-thiols as antiseptics for epithelial tissues, acute and chronic wounds, bacterial biofilms and other indications
US9408393B2 (en) 2010-02-03 2016-08-09 Microbion Corporation Bismuth-thiols as antiseptics for agricultural, industrial and other uses
US9028878B2 (en) 2009-02-03 2015-05-12 Microbion Corporation Bismuth-thiols as antiseptics for biomedical uses, including treatment of bacterial biofilms and other uses
US8389679B2 (en) 2009-02-05 2013-03-05 The Regents Of The University Of California Targeted antimicrobial moieties
WO2010141135A2 (en) 2009-03-05 2010-12-09 Trustees Of Boston University Bacteriophages expressing antimicrobial peptides and uses thereof
ES2528946T3 (es) 2009-03-20 2015-02-13 University Of Virginia Patent Foundation Benzotiofeno-nitrotiazolida y otros antimicrobianos de amplio espectro
GB0905451D0 (en) 2009-03-31 2009-05-13 Novabiotics Ltd Biofilms
AU2009343748B2 (en) 2009-04-01 2013-01-31 Colgate-Palmolive Company Anti-biofilm carbonate compounds for use in oral care compositions
US8852912B2 (en) 2009-04-01 2014-10-07 Danisco Us Inc. Compositions and methods comprising alpha-amylase variants with altered properties
US20120213697A1 (en) 2009-04-21 2012-08-23 Albert Einstein College Of Medicine Of Yeshiva University Versatile nanoparticulate biomaterial for controlled delivery and/or containment of therapeutic and diagnostic material
US8623340B2 (en) 2009-04-28 2014-01-07 Symrise Ag Omega-cyclohexylalkan-1-oles and use thereof as antimicrobial actives to combat body odor
US9539233B2 (en) 2009-05-04 2017-01-10 Aridis Pharmaceuticals Inc. Gallium formulation for the treatment and prevention of infectious diseases
US20110266724A1 (en) 2009-05-08 2011-11-03 Hoowaki, Llc Method for manufacturing microstructured metal or ceramic parts from feedstock
WO2010144686A1 (en) 2009-06-10 2010-12-16 North Carolina State University Inhibition and dispersion of bacterial biofilms with benzimidazole derivatives
US20120149631A1 (en) 2009-06-16 2012-06-14 George Mason Intellectual Properties, Inc Antimicrobial and antibiofilm activity of cathelicidins
EP2443143A4 (en) 2009-06-19 2013-09-11 Oral Health Australia Pty Ltd CASEIN-DERIVED PROTEASE-INHIBITING FIBERS
EP2448930B1 (en) 2009-07-03 2017-02-15 The National Institute for Biotechnology in the Negev Ltd. N-((S)-2-Oxo-tetrahydro-furan-3-yl)-amide derivatives as inhibitors of the bacterial quorum sensing for treating plant or animal diseases and for preventing the formation of biofilms on medical devices
CA2768735A1 (en) 2009-07-20 2011-01-27 Innovotech, Inc. Testing of biofilm for anti-microbial agent susceptibility
CA2768301A1 (en) 2009-07-24 2011-01-27 Southwest Regional Pcr, Llc Universal microbial diagnosis, detection, quantification, and specimen-targeted therapy
US20110177148A1 (en) 2009-07-27 2011-07-21 E. I. Du Pont De Nemours And Company Enzymatic in situ preparation of peracid-based removable antimicrobial coating compositions and methods of use
EP2458985B1 (en) 2009-07-27 2014-11-05 E. I. du Pont de Nemours and Company Enzymatic in situ preparation of peracid-based removable antimicrobial coating compositions and methods of use
US20110182959A1 (en) 2009-07-27 2011-07-28 E.I. Du Pont De Nemours And Company. Removable antimicrobial coating compositions containing acid-activated rheology agent and methods of use
US20120301433A1 (en) 2009-07-29 2012-11-29 Whitehead Institute For Biomedical Research Bacteriophages expressing amyloid peptides and uses thereof
EP2459739B1 (en) 2009-07-30 2016-09-28 Helmholtz-Zentrum für Infektionsforschung GmbH Methods and tests for screening bacterial biofilms
US20110029076A1 (en) 2009-07-30 2011-02-03 Paletta John D Breast Implant Therapeutic Delivery System
US8431151B2 (en) 2009-08-06 2013-04-30 Syracuse University Antimicrobial nanostructured hydrogel web containing silver
EP2464328B1 (en) 2009-08-12 2016-03-30 Colgate-Palmolive Company Oral care composition comprising a sesquiterpenoid and an antimicrobial agent
WO2011022672A1 (en) 2009-08-20 2011-02-24 Allegheny-Singer Research Institute Ultrasound-assisted gene transfer to salivary glands
BR112012003804B1 (pt) 2009-08-21 2019-02-19 Novan, Inc. Curativo para ferimentos, método para formar um curativo para ferimentos, e, kit de curativo para ferimento
ES2958410T3 (es) 2009-08-21 2024-02-08 Novan Inc Geles tópicos
BR112012004175A2 (pt) 2009-08-26 2015-09-08 Basf Se uso de dióis com um grupo cicloalifático, corpo moldado biocidamente acabado, e, preparação líquida.
US20120152149A1 (en) 2009-08-26 2012-06-21 Basf Se Use of 1,3-diols as biocides
US8778387B2 (en) 2009-09-02 2014-07-15 Hyprotek, Inc. Antimicrobial medical dressings and protecting wounds and catheter sites
WO2011034931A2 (en) 2009-09-15 2011-03-24 Reactive Surface, Ltd. Anti-fouling paints and coatings
US20130011332A1 (en) 2009-09-15 2013-01-10 Searete Llc, Frozen Compositions and Methods for Piercing a Substrate
EP2485713B1 (en) 2009-10-05 2018-09-26 Yissum Research Development Company of the Hebrew University of Jerusalem Liquid precursor compositions and uses thereof for a ph-dependant sustained release treatment of oral disorders
US20120201869A1 (en) 2009-10-14 2012-08-09 Burzell Cynthia K Marine bacterial substances, medical devices, and methods for biofilm inhibition
UA111708C2 (uk) 2009-10-16 2016-06-10 Бандж Ойлз, Інк. Спосіб рафінування олії
UA109884C2 (uk) 2009-10-16 2015-10-26 Поліпептид, що має активність ферменту фосфатидилінозитол-специфічної фосфоліпази с, нуклеїнова кислота, що його кодує, та спосіб його виробництва і застосування
US20140200511A1 (en) 2009-10-30 2014-07-17 Searete Llc Systems, devices, and methods for making or administering frozen particles
US8565892B2 (en) 2009-10-31 2013-10-22 Qteris, Inc. Nanoparticle-sized magnetic absorption enhancers having three-dimensional geometries adapted for improved diagnostics and hyperthermic treatment
JP5864429B2 (ja) 2009-11-09 2016-02-17 スポットライト テクノロジー パートナーズ エルエルシーＳｐｏｔｌｉｇｈｔ Ｔｅｃｈｎｏｌｏｇｙ Ｐａｒｔｎｅｒｓ Ｌｌｃ 架橋ヒドロゲル組成物、ヒドロゲル組成物の形成方法、及びキット
EP2498764B1 (en) 2009-11-09 2017-09-06 Spotlight Technology Partners LLC Fragmented hydrogels
JP2013510799A (ja) 2009-11-11 2013-03-28 オーラル ヘルス オーストラリア ピーティーワイ リミテッド 抗バイオフィルム糖ペプチド
US20120289591A1 (en) 2009-11-17 2012-11-15 Michael Anthony Folan Antimicrobial Compositions Containing Free Fatty Acids
US9931381B2 (en) 2009-11-23 2018-04-03 Prothera, Inc. Methods of comprising serratia peptidase for inhibition and treatment of biofilms related to certain conditions
US9591852B2 (en) 2009-11-23 2017-03-14 Mcneil-Ppc, Inc. Biofilm disruptive compositions
US9150453B1 (en) 2009-12-03 2015-10-06 Bowen Li Antimicrobial exfoliated vermiculite composite material and methods for preparing the same
CA2782789A1 (en) 2009-12-09 2011-06-16 Kci Licensing, Inc. Inhibiting bacterial infection and biofilm formation
WO2011072392A1 (en) 2009-12-14 2011-06-23 Innovotech, Inc. Silver (iii) periodates for preventing or reducing microbial contamination, and method for their synthesis
EP2513064B1 (en) 2009-12-17 2018-07-04 Katholieke Universiteit Leuven, K.U. Leuven R&D Compounds, compositions and methods for controlling biofilms
GB0922623D0 (en) 2009-12-23 2010-02-10 Cambridge Entpr Ltd Methods for the purification of cucurbituril
KR20120113259A (ko) 2010-01-08 2012-10-12 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 생물막의 처리에서 사용하기 위한 ｄ-아미노산
WO2011088401A2 (en) 2010-01-15 2011-07-21 Board Of Regents, The University Of Texas System Development of a high-throughput screen for the identification of novel antifungal drug candidates
GB201000916D0 (en) 2010-01-21 2010-03-10 Adv Med Solutions Ltd Treatment of biofilms
CN103108643B (zh) 2010-01-22 2016-10-26 希普罗特克有限公司 包含过氧化物、醇和螯合剂的抗菌剂
KR20130001226A (ko) 2010-01-28 2013-01-03 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 미생물 부착 방지용 구조
GB2477914B (en) 2010-02-12 2012-01-04 Univ Newcastle Compounds and methods for biofilm disruption and prevention
NL2004260C2 (en) 2010-02-18 2011-08-22 Univ Amsterdam Disinfectant composition and its use in dental treatment.
EA201290811A1 (ru) 2010-02-19 2013-03-29 Дзе Юниверсити Оф Саут Дакота Противогрибковые материалы многократного и длительного действия для зубных протезов
WO2011103452A1 (en) 2010-02-19 2011-08-25 Toray Plastics (America) , Inc. Multi-layer high moisture barrier polylactic acid film
MY162557A (en) 2010-02-26 2017-06-15 Oral Health Australia Pty Ltd Treatment or prevention of infection
US20110236769A1 (en) 2010-03-23 2011-09-29 Xing Xie Three dimensional electrodes useful for microbial fuel cells
DE102010013274A1 (de) 2010-03-29 2011-11-17 Beiersdorf Ag Mikrobiologisch stabile anwendungsfreundliche Zubereitungen
WO2011126898A2 (en) 2010-03-30 2011-10-13 Sparkmed Research, Llc Drug releasing medical catheters, tubes, and devices
SI2558577T1 (sl) 2010-04-16 2019-05-31 Nuevolution A/S Bifunkcionalni kompleksi in metode za pripravo in uporabo takšnih kompleksov
SG185528A1 (en) 2010-05-14 2012-12-28 Agency Science Tech & Res Novel antimicrobial compounds and uses thereof
US9073884B2 (en) 2010-06-04 2015-07-07 The Regents Of The University Of California Anti-inflammatory and quorum sensing inhibition compounds and methods of making and using them
NZ603705A (en) 2010-06-09 2014-10-31 Semprus Biosciences Corp Non-fouling, anti-microbial, anti-thrombogenic graft-from compositions
WO2011156603A2 (en) 2010-06-09 2011-12-15 Semprus Biosciences Corp. Articles having non-fouling surfaces and processes for preparing the same without altering bulk physical properties
US20110305898A1 (en) 2010-06-09 2011-12-15 Zheng Zhang Non-fouling, anti-microbial, anti-thrombogenic graft compositions
WO2012012158A2 (en) 2010-06-30 2012-01-26 Schlumberger Canada Limited Bacterial control of water based fluids during subsurface injection and subsequent residence time in the subterranean formation
US9084902B2 (en) 2010-06-30 2015-07-21 Mcneil-Ppc, Inc. Non-alchohol bioactive essential oil mouth rinses
US8889196B2 (en) 2010-06-30 2014-11-18 University Of Maryland, Baltimore Dental composites comprising nanoparticles of amorphous calcium phosphate
FR2962221A1 (fr) 2010-07-02 2012-01-06 Biofilm Control Procede de detection d'interactions moleculaires
SG186782A1 (en) 2010-07-02 2013-02-28 Holden Brien Vision Inst Composition for prevention and treatment of contact lens papillary conjunctivitis and allergic eye disease
WO2012006276A1 (en) 2010-07-06 2012-01-12 North Carolina State University Inhibition of bacterial biofilms with aryl carbamates
MX2013000161A (es) 2010-07-07 2013-09-06 Univ New Jersey Med Metodos de modulacion inmunologica.
IT1401498B1 (it) 2010-07-30 2013-07-26 Mero Srl Idrogelo a base di acido ialuronico e suo uso in ortopedia
GB201013307D0 (en) 2010-08-09 2010-09-22 Univ St Andrews Anti-microbial metal organic framework
EP3804521A1 (en) 2010-08-20 2021-04-14 Innovotech Inc. Silver iodate compounds having antimicrobial properties
US9131687B2 (en) 2010-08-20 2015-09-15 President And Fellows Of Harvard College Roseobacticides and uses thereof
US20120052052A1 (en) 2010-08-27 2012-03-01 The Regents Of The University Of Michigan Control of biofilm formation
WO2012030645A1 (en) 2010-08-30 2012-03-08 Pulmatrix, Inc. Respirably dry powder comprising calcium lactate, sodium chloride and leucine
WO2012030664A1 (en) 2010-08-30 2012-03-08 Pulmatrix, Inc. Dry powder formulations and methods for treating pulmonary diseases
US9125408B2 (en) 2010-09-01 2015-09-08 North Carolina State University Use of aryl carbamates in agriculture and other plant-related areas
US9565857B2 (en) 2010-09-10 2017-02-14 Board Of Regents, The University Of Texas System Antimicrobial solutions
US8383582B2 (en) 2010-09-23 2013-02-26 Industry Foundation Of Chonnam National University Inhibitor against forming biofilm comprising κ-casein macropeptide
ES2899621T3 (es) 2010-09-29 2022-03-14 Pulmatrix Operating Co Inc Polvos secos catiónicos que comprenden sal de magnesio
IL286573B (en) 2010-09-29 2022-08-01 Pulmatrix Operating Co Inc Monovalent metallic cation dry powders for inhalation
EP2624702B1 (en) 2010-10-06 2016-03-02 The Board of Trustees of The University of Arkansas Anti-biofilm compositions and methods for using
US20120087887A1 (en) 2010-10-07 2012-04-12 Biolife, L.L.C. Composition and Method for Arresting Blood Flow and for Forming a Persistent Microbial Barrier
US20120094007A1 (en) 2010-10-13 2012-04-19 Basf Se Method for the immobilization of cationic active ingredients on surfaces
KR20130140721A (ko) 2010-10-14 2013-12-24 마이크로파이레틱스 히터스 인터내셔널, 인코포레이티드 항생물막의 나노다공성 나노구조체 및 이의 제조 방법
WO2012058531A2 (en) 2010-10-29 2012-05-03 North Carolina State University Modulation of response regulators by imidazole derivatives
GB201020236D0 (en) 2010-11-30 2011-01-12 Convatec Technologies Inc A composition for detecting biofilms on viable tissues
US20130330386A1 (en) 2010-12-11 2013-12-12 David G. Whitten Structure, synthesis, and applications for conjugated polyampholytes
FR2968558B1 (fr) 2010-12-14 2013-03-22 Ys Lab Composition a base d'extrait d'algues a usage bucco-dentaire
GB201021186D0 (en) 2010-12-14 2011-01-26 Novabiotics Ltd Composition
US8591876B2 (en) 2010-12-15 2013-11-26 Novan, Inc. Methods of decreasing sebum production in the skin
US8684732B2 (en) 2010-12-15 2014-04-01 Bennett Jacoby System and method for prevention and treatment of peri-implant infection
US10143778B2 (en) 2010-12-21 2018-12-04 Cormatrix Cardiovascular, Inc Cardiovascular prostheses
US10201636B2 (en) 2010-12-20 2019-02-12 Cormatrix Cardiovascular, Inc. Cardiovascular prostheses
US20170100513A1 (en) 2010-12-20 2017-04-13 Cormatrix Cardiovascular, Inc. Cardiovascular Prostheses
CA2822422C (en) 2010-12-20 2021-02-02 E. I. Du Pont De Nemours And Company Enzymatic peracid generation for use in oral care products
US10273205B2 (en) 2011-01-03 2019-04-30 The William M. Yarbrough Foundation Isothiocyanate functional surfactants, formulations incorporating isothiocyanate functional surfactants and associated methods for treating biofilms
US20120178971A1 (en) 2011-01-06 2012-07-12 Aligarh Muslim University Process for Isolation of a Novel Compound 5,8A-DI-1-Propyl 1-Octahydronapthalen-1-(2H) One,Trachyspermum AMI (Ajowan Caraway) Seeds
CA2825012C (en) 2011-01-19 2021-03-23 President And Fellows Of Harvard College Slippery liquid-infused porous surfaces and biological applications thereof
US8906393B2 (en) 2011-01-26 2014-12-09 Rutgers, The State University Of New Jersey Biofilm inhibiting composition
US10064858B2 (en) 2011-01-31 2018-09-04 The United States Of America, As Represented By The Secretary Of The Army Methods and compositions for treating bacterial infections with iron chelators
US9198957B2 (en) 2011-01-31 2015-12-01 The Trustees Of Columbia University In The City Of New York Treatment and prevention of bacterial vaginosis and Gardnerella vaginalis infections
US20170100328A1 (en) 2011-02-04 2017-04-13 Joseph E. Kovarik Bioadhesive Strip and Method of Using Same
US10010568B2 (en) 2011-02-04 2018-07-03 Katherine Rose Kovarik Method and system for reducing the likelihood of a spirochetes infection in a human being
ES2732311T3 (es) 2011-02-07 2019-11-21 Univ Washington Compuestos de manósidos y procedimientos de uso de los mismos
US8710082B2 (en) 2011-02-18 2014-04-29 Board Of Trustees Of Michigan State University Benzimidazole inhibition of biofilm formation
WO2012118829A2 (en) 2011-02-28 2012-09-07 Novan, Inc. Tertiary s-nitrosothiol-modified nitricoxide-releasing xerogels and methods of using the same
EP2680866A1 (en) 2011-03-01 2014-01-08 Quorum Innovations, LLC Materials and methods for treating conditions associated with pathogenic biofilm
WO2012126899A2 (en) 2011-03-18 2012-09-27 Katholieke Universiteit Leuven Ku Leuven Research & Development Inhibition and treatment of biofilms
WO2012129515A1 (en) 2011-03-23 2012-09-27 University Of Medicine And Dentistry Of New Jersey Transgenic plants expressing dispersinb
US8952192B2 (en) 2011-03-24 2015-02-10 University Of Maryland, College Park Phosphorylated and branched dihydroxy-pentane-dione (DPD) analogs as quorum sensing inhibitors in bacteria
WO2012135016A2 (en) 2011-03-25 2012-10-04 North Carolina State University Inhibition of bacterial biofilms and microbial growth with imidazole derivatives
WO2012131669A1 (en) 2011-03-29 2012-10-04 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. Film-forming composition for a ph-dependant sustained release of the active agent
WO2012135615A2 (en) 2011-03-30 2012-10-04 Brown University Enopeptins, uses thereof, and methods of synthesis thereto
CA2830566A1 (en) 2011-04-01 2012-10-04 General Electric Company Methods and compositions for remediating microbial induced corrosion and environmental damage and for improving wastewater treatment processes
GB201105829D0 (en) 2011-04-06 2011-05-18 Convatec Technologies Inc Antimicrobial compositions
US20120263793A1 (en) 2011-04-14 2012-10-18 Franco Vitaliano Bio-nano-plasmonic elements and platforms
WO2012145680A2 (en) 2011-04-21 2012-10-26 George Mason Intellectual Properties, Inc. Anti-microbial peptides and uses therefore
EP2702141B1 (en) 2011-04-25 2018-03-14 California Institute of Technology Methods and system for interfering with viability of bacteria and related compounds and compositions
US9566341B1 (en) 2011-04-27 2017-02-14 University Of Kentucky Research Foundation Compounds including Cox inhibitor moiety and enhanced delivery of active drugs using same
GB2490516A (en) 2011-05-03 2012-11-07 Systagenix Wound Man Ip Co Bv Polysaccharide mould for wound treatment
WO2012151554A1 (en) 2011-05-04 2012-11-08 President And Fellows Of Harvard College Polyamines for treating biofilms
CN103502434B (zh) 2011-05-06 2016-08-17 有机平衡医疗股份公司 乳酸菌以及含有该乳酸菌的组合物
DK2710016T3 (en) 2011-05-16 2016-08-15 Newsouth Innovations Pty Ltd REGULATION OF NITROGEN OXIDE RELEASE AND BIOFILM DEVELOPMENT
US9155310B2 (en) 2011-05-24 2015-10-13 Agienic, Inc. Antimicrobial compositions for use in products for petroleum extraction, personal care, wound care and other applications
US20160032180A1 (en) 2012-11-26 2016-02-04 Agienic, Inc. Antimicrobial Resin Coated Proppants
US20130315972A1 (en) 2012-05-24 2013-11-28 Agienic, Inc. Compositions and methods for antimicrobial metal nanoparticles
US10016525B2 (en) 2011-05-24 2018-07-10 Agienic, Inc. Antimicrobial compositions for use in wound care products
CN104039812A (zh) 2011-05-31 2014-09-10 和黄生物膜医疗解决方案有限公司 细胞聚集体的分散和脱离
US8257827B1 (en) 2011-06-02 2012-09-04 The Regents Of The University Of California Silicone composition and devices incorporating same
EP2532232A1 (en) 2011-06-10 2012-12-12 InterMed Discovery GmbH Long chain glycolipids useful to avoid perishing or microbial contamination of materials
US20120315260A1 (en) 2011-06-13 2012-12-13 Svetlana A. Ivanova Compositions and Methods to Prevent and Treat Biofilms
US10420822B2 (en) 2011-06-13 2019-09-24 Ziolase, Llc Compositions and methods to prevent and treat biofilms
TWI415572B (zh) 2011-06-17 2013-11-21 Univ Chang Gung 利用１，２，３，４，６－五－ｏ－沒食子醯基－ｄ－葡哌喃糖來抑制生物膜形成
US8609110B2 (en) 2011-06-21 2013-12-17 University of Pittsburgh—of the Commonwealth System of Higher Education Citrobacter freundii antibacterial agents and their use
JP2014520199A (ja) 2011-06-23 2014-08-21 ビーエーエスエフ エスイー 広範囲抗菌剤としてのアルキルアミノアルキルオリゴマー
EP2729131B1 (en) 2011-07-05 2020-04-15 Novan, Inc. Topical compositions
WO2013006613A1 (en) 2011-07-05 2013-01-10 Novan, Inc. Methods of manufacturing topical compositions and apparatus for same
EP2734519B1 (en) 2011-07-22 2016-05-04 University Of Louisville Research Foundation, Inc. Anti-biofilm compounds
US20130039978A1 (en) 2011-08-09 2013-02-14 Joseph Schwarz Medicinal compositions and method for treatment of urinary tract infections
US8999265B2 (en) 2011-08-10 2015-04-07 State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University Bonding agent and device for use in microfluidics
JP5969484B2 (ja) 2011-08-22 2016-08-17 テルモ株式会社 抗血栓性材料および医療用具
WO2013026150A1 (en) 2011-08-22 2013-02-28 Innovotech, Inc. A family of silver(i) periodate compounds having broad antimicrobial properties
US9603877B2 (en) 2011-08-31 2017-03-28 Nanyang Technological University Isolated nucleotide molecule and method of sensing and killing of pathogenic microorganism
JP6151257B2 (ja) 2011-09-09 2017-06-21 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． 肺内感染症の治療方法
CA2846893A1 (en) 2011-09-09 2013-03-14 Greenlight Biosciences, Inc. Cell-free preparation of carbapenems
US9603859B2 (en) 2011-09-13 2017-03-28 Brigham Young University Methods and products for increasing the rate of healing of tissue wounds
US20130245116A1 (en) 2011-09-16 2013-09-19 U.S. Department Of Veterans Affairs Compositions and methods for the disruption of mycobacterium biofilm
CN104080505B (zh) 2011-09-30 2017-01-18 麦德卡斯特思公司 将药物分子嵌入医用导管或管的系统、器械和方法
US20140336159A1 (en) 2011-10-07 2014-11-13 Pulmatrix, Inc. Methods for treating and diagnosing respiratory tract infections
US20190134151A1 (en) 2011-10-07 2019-05-09 Morehouse School Of Medicine Antibacterial compositions, methods of making and use thereof
WO2013063354A1 (en) 2011-10-27 2013-05-02 Novan, Inc. Nitric oxide releasing bath compositions and methods of using the same
US11090366B2 (en) 2011-10-31 2021-08-17 Kane Biotech Inc. Compositions and methods for reducing oral biofilm
EP2589381B1 (en) 2011-11-04 2016-08-31 Rabindra Tirouvanziam Compositions for improving or preserving lung function in a patient with a pulmonary disorder
US10292390B2 (en) 2011-11-04 2019-05-21 Wisconsin Alumni Research Foundation Inhibition and dispersion of bacterial biofilms with 2-aminobenzimidazole derivatives
WO2013115868A2 (en) 2011-11-04 2013-08-08 President And Fellows Of Harvard College Dynamic and switchable slippery surfaces
AU2012332054A1 (en) 2011-11-04 2014-06-26 Oral Health Australia Pty Ltd Gingipain inhibitory propeptides
US20130123319A1 (en) 2011-11-15 2013-05-16 Thomas Benedict Bryan Medthod of Treating a systemic inflammatory disorder and damaged internal tissues
US8829053B2 (en) 2011-12-07 2014-09-09 Rochal Industries Llp Biocidal compositions and methods of using the same
TWI487543B (zh) 2011-12-12 2015-06-11 Ind Tech Res Inst 梳狀結構高分子、醫療裝置的改質方法及醫療裝置
WO2013090185A1 (en) 2011-12-13 2013-06-20 Polymedix, Inc. Cyclic compounds and methods of making and using the same
US20130158127A1 (en) 2011-12-14 2013-06-20 Jean-Christophe Sergere Tea tree oil derivatives
MX2014007208A (es) 2011-12-14 2015-04-14 Semprus Biosciences Corp Modificacion en la superficie para cateteres de dialisis.
MX2014007209A (es) 2011-12-14 2015-04-14 Semprus Biosciences Corp Modificacion en la superficie para cateteres comprendidos de multiples materiales.
AU2012352139A1 (en) 2011-12-14 2014-07-03 Semprus Biosciences Corp. Luminal modifications for catheters
WO2013089735A1 (en) 2011-12-15 2013-06-20 Colgate-Palmolive Company Oral care compositions
US9919079B2 (en) 2011-12-16 2018-03-20 Cormatrix Cardiovascular, Inc. Cardiovascular prostheses
US20170100516A1 (en) 2011-12-16 2017-04-13 Cormatrix Cardiovascular, Inc. Cardiovascular Prostheses
US20170100512A1 (en) 2011-12-16 2017-04-13 Cormatrix Cardiovascular, Inc. Cardiovascular Prostheses
US20170100514A1 (en) 2011-12-16 2017-04-13 Cormatrix Cardiovascular, Inc. Cardiovascular Prostheses
US20170100517A1 (en) 2011-12-16 2017-04-13 Cormatrix Cardiovascular, Inc. Cardiovascular Prostheses
US20130164228A1 (en) 2011-12-21 2013-06-27 Colgate-Palmolive Company Compositions comprising gallates and gallamides
US20140322362A1 (en) 2011-12-22 2014-10-30 Bromine Compounds Ltd. In situ production of a biocidal bromine species via electrolysis
WO2013103514A1 (en) 2012-01-04 2013-07-11 The Trustees Of The Stevens Institute Of Technology Clay-containing thin films as carriers of absorbed molecules
US8840912B2 (en) 2012-01-09 2014-09-23 North Carolina State University Imidazole derivatives useful for controlling microbial growth
EP2802630B1 (en) 2012-01-10 2018-05-30 President and Fellows of Harvard College Modification of surfaces for fluid and solid repellency
FR2985667B1 (fr) 2012-01-12 2014-08-22 Univ Dauvergne Clermont I Composition verrou aqueuse comprenant de l'ethanol et un anticoagulant polysaccharidique
US20130183435A1 (en) 2012-01-13 2013-07-18 Hongmin Sun Low temperature plasma coating for anti-biofilm formation
US8641686B2 (en) 2012-01-20 2014-02-04 Rabie Stephan Anti-biofilm intravascular catheter
WO2013119901A1 (en) 2012-02-10 2013-08-15 University Of Maryland Nanostructured antibacterial and remineralizing dental bonding agents and dental bonding systems
US9359275B2 (en) 2012-02-23 2016-06-07 Children's Medical Center Corporation Natural product antibiotics and analogs thereof
US8545951B2 (en) 2012-02-29 2013-10-01 Kimberly-Clark Worldwide, Inc. Endotracheal tubes and other polymer substrates including an anti-fouling treatment
WO2013130767A1 (en) 2012-02-29 2013-09-06 Pulmatrix, Inc. Inhalable dry powders
SG11201405359YA (en) 2012-03-01 2014-09-26 Firststring Res Inc Topical gels containing alpha connexin c-terminal (act) peptides
JP6204930B2 (ja) 2012-03-05 2017-09-27 ユニバーシティ オブ メリーランド，ボルチモア 多価ワクチンによる黄色ブドウ球菌感染症からの保護
US11077194B2 (en) 2012-03-14 2021-08-03 Novan, Inc. Nitric oxide releasing pharmaceutical compositions
WO2013142372A1 (en) 2012-03-20 2013-09-26 Kci Licensing, Inc. Targeted enzymatic degradation of quorum-sensing peptides
CA2867733C (en) 2012-03-22 2020-04-07 The Governing Council Of The University Of Toronto Multi-functional micro and nanoparticles for use in root canal therapies
US20130252818A1 (en) 2012-03-23 2013-09-26 Los Alamos National Security, Llc Amorphous bioinorganic ionic liquid compositions comprising agricultural substances
AU2013235336B2 (en) 2012-03-23 2016-09-08 Amicrobe, Inc. Compositions and uses of antimicrobial materials with tissue-compatible properties
NZ700295A (en) 2012-03-28 2016-07-29 Arla Foods Amba Nanoparticle aggregates containing osteopontin and calcium- and/or strontium-containing particles
CA2867787C (en) 2012-03-30 2022-01-04 Dentsply Ih Ab A medical device having a surface comprising antimicrobial metal
US20160089481A1 (en) 2012-03-30 2016-03-31 Dentsply International Inc. Medical device having a surface comprising gallium oxide
US9273084B2 (en) 2012-04-06 2016-03-01 President And Fellows Of Harvard College Moenomycin analogs, methods of synthesis, and uses thereof
US9452107B2 (en) 2012-04-16 2016-09-27 New Jersey Institute Of Technology Systems and methods for superdisintegrant-based composite particles for dispersion and dissolution of agents
US20130288951A1 (en) 2012-04-27 2013-10-31 Biomet Manufacturing Corp. Compositions and methods for coating implant surfaces to inhibit surgical infections
AU2013251346B2 (en) 2012-04-27 2016-12-22 Biomet Manufacturing, Llc Compositions and methods for coating implant surfaces to inhibit surgical infections
US10441588B2 (en) 2012-05-02 2019-10-15 Curators Of The University Of Missouri Methods and compositions for treating bacterial infection
WO2013166282A2 (en) 2012-05-02 2013-11-07 The Regents Of The University Of Michigan Methods and compositions for treating bacterial infection
US9814719B2 (en) 2012-05-02 2017-11-14 Curators Of The University Of Missouri Methods and compositions for treating bacterial infection
KR20230135161A (ko) 2012-05-09 2023-09-22 콘트라펙트 코포레이션 박테리오파지 리신을 이용한 생물막의 예방, 붕괴 및 치료
RU2014145270A (ru) 2012-05-11 2016-07-10 Смит & Невью, Инк. Способ и композиция для разрушения бактериальной биопленки
WO2013171372A1 (en) 2012-05-14 2013-11-21 Nordichug Oy Aqueous disinfectant composition
US10681914B2 (en) 2012-05-29 2020-06-16 Neozyme International, Inc. Non-toxic plant agent compositions and methods and uses thereof
EP2854888B1 (en) 2012-05-31 2019-07-10 Baylor College Of Medicine Lipoic acid compositions useful as antimicrobial agents
US20130330388A1 (en) 2012-06-12 2013-12-12 Mattech, Inc. Porous Sphere-like Objects, Method to Form Same and Uses Thereof Involvoing the Treatment of Fluids Including Anti-bacterial Applications
EP2861066A1 (en) 2012-06-19 2015-04-22 The Board of Trustees of The Leland Stanford Junior University Curcumin derivatives for microbial biofilm destruction
FR2992318B1 (fr) 2012-06-22 2018-11-16 Centre Nat Rech Scient Materiaux hybrides peptide-silice
US20140005605A1 (en) 2012-06-28 2014-01-02 Pacesetter, Inc. Use of quorum sensing inhibitors and biofilm dispersing agents for controlling biofilm-associated implantable medical device related infections
CA2876163C (en) 2012-06-29 2019-09-10 Colgate-Palmolive Company High water content oral compositions comprising microcrystalline cellulose and carboxymethylcellulose
CA2878292A1 (en) 2012-07-05 2014-01-09 The Research Foundation For The State University Of New York Potentiation of antibiotic treatment with a protein-lipid complex
US10569038B2 (en) 2012-07-06 2020-02-25 The Regents Of The University Of California Dual lumen endobronchial tube device
FR2992862B1 (fr) 2012-07-09 2014-10-03 Fabre Pierre Dermo Cosmetique Utilisation d'un extrait de myrte en tant qu'agent anti-biofilm vis-a-vis de p. acnes
US20150159180A1 (en) 2012-07-16 2015-06-11 Council Of Scientific & Industrial Research Process for production of crystalline xylitol using pichia caribbica and its application for quorum sensing inhibition
US9540471B2 (en) 2012-07-17 2017-01-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nitric oxide-releasing diazeniumdiolated polyvinylpyrrolidone-based polymers, and compositions, medical devices, and uses thereof
EP2875078B1 (en) 2012-07-18 2017-12-20 President and Fellows of Harvard College Modification of surfaces for simulataneous repellency and targeted binding of desired moieties
WO2014012171A1 (en) 2012-07-19 2014-01-23 Innovotech, Inc. Anti-microbial gel formulations containing a silver (i) periodate
US8940911B2 (en) 2012-08-01 2015-01-27 Syracuse University Squarylated lactones inhibitors for bacterial biofilm formation
US20150182667A1 (en) 2012-08-08 2015-07-02 Vanderbilt University Composition with Biofilm Dispersal Agents
US9243036B2 (en) 2012-08-15 2016-01-26 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-microbial activity of synthetic peptides
WO2014028847A1 (en) 2012-08-17 2014-02-20 The University Of North Carolina At Chapel Hill Water soluble nitric oxide-releasing polyglucosamines and uses thereof
WO2014028848A1 (en) 2012-08-17 2014-02-20 The Regents Of The University Of Michigan Compositions and method for treating neutralizing microorganisms
US9187501B2 (en) 2012-08-28 2015-11-17 The University Of North Carolina At Chapel Hill Nitric oxide-releasing nanorods and their methods of use
WO2014035345A1 (en) 2012-08-29 2014-03-06 Agency For Science, Technology And Research Peptides and uses thereof
US9648880B2 (en) 2012-09-04 2017-05-16 University Of Massachusetts Antifungal agents and uses thereof
US20140072525A1 (en) 2012-09-07 2014-03-13 Gaab, Llc Antimicrobial preparation and methods for making and using the same
US8809314B1 (en) 2012-09-07 2014-08-19 Cubist Pharmacueticals, Inc. Cephalosporin compound
WO2014037528A1 (en) 2012-09-07 2014-03-13 Analyticon Discovery Gmbh Composition comprising licoricidine
EP2897574A2 (en) 2012-09-07 2015-07-29 AnalytiCon Discovery GmbH Anti-dandruff composition comprising 1-acetoxychavicol acetate
US9987316B2 (en) 2012-09-14 2018-06-05 Case Western Reserve University Probiotic controlling fungi and uses thereof
US8476425B1 (en) 2012-09-27 2013-07-02 Cubist Pharmaceuticals, Inc. Tazobactam arginine compositions
US9566372B2 (en) 2012-09-28 2017-02-14 The Regents Of The University Of Michigan Sustained nitric oxide release coating using diazeniumdiolate-doped polymer matrix with ester capped poly(lactic-co-glycolic acid) additive
WO2014055127A1 (en) 2012-10-03 2014-04-10 Ribbeck Katharina Methods of inhibiting surface attachment of microorganisms
IN2015DN02960A (zh) 2012-10-09 2015-09-18 Dentsply Int Inc
US20150299345A1 (en) 2012-10-16 2015-10-22 University Of Maryland, Baltimore Antibacterial monomers, antibacterial resins and dental composites comprising the antibacterial resins
WO2014066674A1 (en) 2012-10-24 2014-05-01 Kci Licensing, Inc. Amine-functionalized polymeric compositions for medical devices
JP6334550B2 (ja) 2012-11-06 2018-05-30 インベッド バイオサイエンシズ，インコーポレイテッド 創傷治癒の方法と組成物
US11352551B2 (en) 2012-11-26 2022-06-07 Agienic, Inc. Proppant coatings containing antimicrobial agents
BR112015012123A8 (pt) 2012-11-26 2018-01-23 Borody Thomas J composições para a recuperação de uma microbiota fecal e métodos para produzir e usar as mesmas.
US10208241B2 (en) 2012-11-26 2019-02-19 Agienic, Inc. Resin coated proppants with antimicrobial additives
US9642829B2 (en) 2012-12-04 2017-05-09 The University Of Hong Kong Antifungal compound and uses thereof
JP2014113082A (ja) 2012-12-07 2014-06-26 Fujifilm Corp 液面上での微細藻類の培養方法において、液面上の微細藻類から種藻を採取し、別の培養容器で培養を行う方法
US20140308317A1 (en) 2012-12-10 2014-10-16 Cellceutix Corporation Polymeric Compounds And Methods Of Making And Using The Same
WO2014093231A2 (en) 2012-12-10 2014-06-19 Cellceutix Corporation Hybrid compounds and methods of making and using the same
WO2014092747A1 (en) 2012-12-12 2014-06-19 William Wingfield Metal oxide complexes and infusion of complexes into polymer compounds
CN104995261B (zh) 2012-12-13 2018-09-21 工业研究与发展基金会有限公司 疏水和疏油表面及其用途
WO2014099923A1 (en) 2012-12-18 2014-06-26 Basf Se Improved antimicrobial effects in polymers
BR112015014831A2 (pt) 2012-12-19 2017-07-11 Johnson & Johnson Consumer Companies Inc partículas anidras de pó a líquido
US9770418B2 (en) 2013-01-07 2017-09-26 Bar-Ilan University Dopamine nanocapsules and uses thereof
AU2014206502B2 (en) 2013-01-16 2019-10-03 The State Of Israel, Ministry Of Agriculture & Rural Development, Agricultural Research Organization (Aro) (Volcani Center) Melanoidins and their use for improving properties of plants
KR20150110554A (ko) 2013-01-25 2015-10-02 케미라 오와이제이 살생물제 조성물 및 수처리 방법
US9862837B2 (en) 2013-01-31 2018-01-09 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd Antifouling materials
CA2899384A1 (en) 2013-01-31 2014-08-07 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Antifouling materials
RU2723946C2 (ru) 2013-02-05 2020-06-18 Юниверсити Оф Сэскэтчевэн Эндофитные микробные симбионты в пренатальном уходе за растениями
EP2953660B1 (en) 2013-02-07 2020-04-01 The Regents Of The University Of Michigan Thromboresistant/bactericidal s-nitroso-n-acetylpenicillamine (snap)-doped nitric oxide release polymers with enhanced stability
US20150044147A1 (en) 2013-02-18 2015-02-12 King Abdullah International Medical Research Center Composition for management of periodontal disease
US20140234380A1 (en) 2013-02-18 2014-08-21 King Abdullah International Medical Research Center Composition for management of periodontal disease
CA2902157A1 (en) 2013-02-25 2014-08-28 University Of Rochester Nanoparticles for controlled release of anti-biofilm agents
US9855211B2 (en) 2013-02-28 2018-01-02 Novan, Inc. Topical compositions and methods of using the same
US10357470B2 (en) 2013-03-07 2019-07-23 Kane Biotech Inc. Antimicrobial-antibiofilm compositions and methods of use thereof
WO2014134731A1 (en) 2013-03-07 2014-09-12 Kane Biotech Inc. Antimicrobial-antibiofilm compositions and methods of use thereof
WO2014164694A1 (en) 2013-03-11 2014-10-09 University Of Florida Research Foundation, Inc. Application of biofilm formation inhibiting compounds enhances control of citrus canker
EP2968080B1 (en) 2013-03-12 2023-05-10 Synedgen, Inc. Oral formulation of polyglucosamine derivatives in combination with a non-fermentable sugar
EP2968083B1 (en) 2013-03-12 2021-09-22 Primal Therapies, Inc. Dental composition comprising chelator and base
US9423532B2 (en) 2013-03-12 2016-08-23 Intermolecular, Inc. Anti-reflection coatings with aqueous particle dispersions and methods for forming the same
US9439803B2 (en) 2013-03-13 2016-09-13 Carefusion 2200, Inc. Patient warming device with patient access
US20140276254A1 (en) 2013-03-13 2014-09-18 Carefusion 2200, Inc. Patient warming and dvt prevention system
US9433527B2 (en) 2013-03-13 2016-09-06 Carefusion 2200, Inc. Compressive patient warming device
US10202631B2 (en) 2013-03-14 2019-02-12 University Of Cincinnati Multi-tiered, high through-put screen for compounds effective against bacterial biofilm compounds effective for inhibiting and eradicating bacterial biofilm
US10272098B2 (en) 2013-03-14 2019-04-30 Drexel University Chelated drug delivery systems
CA3123075C (en) 2013-03-14 2023-09-19 The Regents Of The University Of California Thiosaccharide mucolytic agents
US9872906B2 (en) 2013-03-15 2018-01-23 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions
US20160045841A1 (en) 2013-03-15 2016-02-18 Transtar Group, Ltd. New and improved system for processing various chemicals and materials
US9775853B2 (en) 2013-03-15 2017-10-03 Biomet Manufacturing, Llc. Hemostatic compositions and methods
EP2967967B1 (en) 2013-03-15 2019-09-25 Griffith, Donald Systems and methods for microbial resistance zones
EP3100732A1 (en) 2013-03-15 2016-12-07 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions
GEP20237544B (en) 2013-03-15 2023-09-25 Jeneil Biosurfactant Company Llc Us Antimicrobial compositions and related methods of use
US20140274993A1 (en) 2013-03-15 2014-09-18 Cubist Pharmaceuticals, Inc. Ceftolozane-tazobactam pharmaceutical compositions
US9562254B2 (en) 2013-03-19 2017-02-07 Colgate-Palmolive Company Anti-biofilm screening assays
US9402394B2 (en) 2013-04-04 2016-08-02 University Of South Carolina Anion-paired cationic metallocene-containing compounds and polymers as antimicrobial agents
US10532202B2 (en) 2013-05-02 2020-01-14 Vomaris Innovations, Inc. Methods and devices for cellular activation
JP6142076B2 (ja) 2013-05-03 2017-06-07 マイクロバイオティックス・インコーポレーテッド 抗微生物性増強剤
JP2016525998A (ja) 2013-05-06 2016-09-01 バル・イラン・ユニバーシティＢａｒ Ｉｌａｎ Ｕｎｉｖｅｒｓｉｔｙ ドープ化金属酸化物ナノ粒子及びその使用
MX364942B (es) 2013-05-10 2019-05-15 Academisch Ziekenhuis Leiden Peptidos antimicrobianos.
AU2014266070A1 (en) 2013-05-17 2015-12-10 Alequident Limited Oral healthcare product
US9612246B2 (en) 2013-05-21 2017-04-04 University Of Washington Though Its Center For Commercialization Real-time analysis for cross-linked peptides
US9034927B2 (en) 2013-05-22 2015-05-19 Curza Global, Llc Methods of use for compositions comprising a biocidal polyamine
US9439433B2 (en) 2013-05-22 2016-09-13 Curza Global, Llc Compositions and methods comprising a biocidal polyamine
US9387189B2 (en) 2013-05-22 2016-07-12 Professional Compounding Centers Of America (Pcca) Antibiotic composition comprising a chemotactic agent and a nutrient dispersion
PE20160473A1 (es) 2013-05-29 2016-05-22 Aguas De Manizales S A E S P Composiciones para tratamiento de aguas y metodos para uso de las mismas
EP3003322B1 (en) 2013-05-30 2023-09-13 Washington University Mannose derivatives and their use in the treatment of bacterial infections
US9340802B2 (en) 2013-06-20 2016-05-17 Lanzatech New Zealand Limited Fermentation of gaseous substrates
US9744270B2 (en) 2013-06-20 2017-08-29 The Governors Of The University Of Alberta Nanocrystalline cellulose hydrogels for inhibition of bacterial adhesion
US10821178B2 (en) 2013-07-29 2020-11-03 Board Of Regents Of The University Of Nebraska Methods of treating biofilm infections comprising administering inhibitors of myeloid-derived suppressor cells
WO2015017258A1 (en) 2013-08-01 2015-02-05 Murphy Christopher J Method of characterizing wounds with raman spectroscopy
US9694114B2 (en) 2013-08-07 2017-07-04 Arrow International, Inc. Antimicrobial catheters with permeabilization agents
BR112016002387B1 (pt) 2013-08-08 2019-05-21 Novan, Inc. Composições farmacêuticas tópicas, e método para seu armazenamento
US10206947B2 (en) 2013-08-08 2019-02-19 Novan, Inc. Topical compositions and methods of using the same
WO2015038339A1 (en) 2013-08-27 2015-03-19 The University Of British Columbia Small cationic anti-biofilm and idr peptides
US11759186B2 (en) 2018-06-08 2023-09-19 David S. Goldsmith Ductus side-entry and prosthetic disorder response systems
US11013858B2 (en) 2016-01-12 2021-05-25 David S. Goldsmith Nonjacketing side-entry connectors and prosthetic disorder response systems
US20160113940A1 (en) 2013-09-03 2016-04-28 Biomimetix J.V., Llc Methods of treating biofilms
US10203329B2 (en) 2013-09-12 2019-02-12 The Johns Hopkins University Biofilm formation to define risk for colon cancer
US11684069B2 (en) 2013-09-13 2023-06-27 3M Innovative Properties Company Cationic antiseptic compositions
EP3831374A1 (en) 2013-09-24 2021-06-09 The Regents of The University of Michigan Compositions and method for destabilizing, altering, and dispersing biofilms
US10233234B2 (en) 2014-01-13 2019-03-19 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US20150197558A1 (en) 2013-09-26 2015-07-16 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US20150086561A1 (en) 2013-09-26 2015-03-26 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US20150299298A1 (en) 2013-09-26 2015-10-22 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US8906898B1 (en) 2013-09-27 2014-12-09 Calixa Therapeutics, Inc. Solid forms of ceftolozane
WO2015066238A2 (en) 2013-10-29 2015-05-07 Ultraviolet Interventions Inc. Systems and methods for sterilization using uv light
ES2908345T3 (es) 2013-11-03 2022-04-28 Univ California Líquidos iónicos para la administración transdérmica de medicamentos
CN106102730A (zh) 2013-11-05 2016-11-09 天普大学高等教育联合体 作为抗微生物剂的聚阳离子两亲物
US10398142B2 (en) 2013-11-05 2019-09-03 Temple University Of The Commonwealth System Of Higher Education Polycationic amphiphiles as antimicrobial agents
CN106061252A (zh) 2013-11-05 2016-10-26 天普大学高等教育联合体 作为抗微生物剂的双阳离子和三阳离子两亲物
GB201319621D0 (en) 2013-11-06 2013-12-18 Norwegian University Of Science And Technology Antimicrobial agents and their use in therapy
WO2015071413A1 (en) 2013-11-15 2015-05-21 Universitat Autonoma De Barcelona Wheat bran soluble extract as anti-biofilm agent
US10597314B2 (en) 2013-11-22 2020-03-24 General Electric Company Fatty acid biodispersant and methods of use
US20160296434A1 (en) 2013-11-22 2016-10-13 Colgate-Palmolive Company Tooth whitening oral care product
US20150147775A1 (en) 2013-11-25 2015-05-28 Corning Incorporated Test method for efficacy of silver surfaces as a sanitizer
FR3014336B1 (fr) 2013-12-05 2016-01-22 Commissariat Energie Atomique Utilisation d'un gel alcalin oxydant pour eliminer un biofilm sur une surface d'un substrat solide.
PT3087092T (pt) 2013-12-12 2018-11-09 Academisch Ziekenhuis Leiden Péptido antimicrobiano e utilizações do mesmo
US20170173186A9 (en) 2013-12-13 2017-06-22 Rebecca L. Pavlicek Murine wound model for testing pathogen viruence and therapeutic efficacy
US10092626B2 (en) 2013-12-17 2018-10-09 Yale University Anti-infective properties of antifreeze protein
CA2934523A1 (en) 2013-12-24 2015-07-02 University Of Florida Research Foundation, Inc. Phenazine derivatives as antimicrobial agents
US20150237870A1 (en) 2014-01-22 2015-08-27 The Board Of Regents Of The University Of Texas System Inhibition of biofilm formation with genetically engineered bacteriophages
EP3097128A4 (en) 2014-01-23 2017-08-16 Bar-Ilan University Polyamide nanoparticles and uses thereof
MX2016009898A (es) 2014-01-29 2017-01-23 Vyome Biosciences Pvt Ltd Tratamientos para acne resistente.
DE102014101663A1 (de) 2014-02-11 2015-08-13 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Synthetische artifizielle Peptide mit antimikrobieller Wirkung
US9782388B2 (en) 2014-02-25 2017-10-10 University Of South Florida BIS-cyclic guanidine compound compositions, methods of use and treatment thereof
ES2588395T3 (es) 2014-03-17 2016-11-02 Bonalive Biomaterials Oy Pasta implantable y su uso
US20170014437A1 (en) 2014-04-03 2017-01-19 Syracuse University Synthetic disugar hydrocarbons as natural analogs to control microbial behaviors
EP3126333B1 (en) 2014-04-03 2018-08-01 Helmholtz-Zentrum für Infektionsforschung GmbH Pqsr modulators
US20170173225A1 (en) 2014-04-16 2017-06-22 Biomet Manufacturing, Llc Methods for coating implant surfaces to treat surgical infections
US20150332151A1 (en) 2014-05-13 2015-11-19 Carnegie Mellon University Methods and Software For Determining An Optimal Combination Of Therapeutic Agents For Inhibiting Pathogenesis Or Growth Of A Cell Colony, And Methods Of Treating One Or More Cell Colonies
FR3020948B1 (fr) 2014-05-14 2018-04-06 Melipharm Composition antimicrobienne
US9271502B2 (en) 2014-05-23 2016-03-01 Robert Sabin Potentiation of fixed coppers and other pesticides containing copper and supplementing plant nutrition
US9718739B2 (en) 2014-05-23 2017-08-01 Robert Sabin Potentiation of fixed coppers and other pesticides containing copper and supplementing plant nutrition
US9586871B2 (en) 2014-05-23 2017-03-07 Robert Sabin Potentiation of fixed coppers and other pesticides containing copper and supplementing plant nutrition
US9854807B2 (en) 2014-05-23 2018-01-02 Robert Sabin Potentiation of fixed coppers and other pesticides containing copper and supplementing plant nutrition
US9247734B2 (en) 2014-05-23 2016-02-02 Robert Sabin Potentiation of fixed coppers and other pesticides containing copper and supplementing plant nutrition
US9487453B2 (en) 2014-05-23 2016-11-08 Robert Sabin Potentiation of fixed coppers and other pesticides containing copper and supplementing plant nutrition
KR20170008762A (ko) 2014-05-28 2017-01-24 오스페릭스 리미티드 항균제로서의 금 (i)-포스핀 화합물
EP3148554A1 (en) 2014-05-28 2017-04-05 Auspherix Limited Gold (i)-phosphine compounds as anti-bacterial agents
WO2015187870A1 (en) 2014-06-03 2015-12-10 Vomaris Innovations, Inc. Methods and devices for treating the skin
JP2017524344A (ja) 2014-06-06 2017-08-31 ザ・ホスピタル・フォー・シック・チルドレンＴｈｅ Ｈｏｓｐｉｔａｌ Ｆｏｒ Ｓｉｃｋ Ｃｈｉｌｄｒｅｎ バイオフィルムの阻害及び分散における可溶性細菌及び真菌タンパク質並びに方法並びにそれらの使用
US10155965B2 (en) 2014-06-16 2018-12-18 Institut Pasteur Production of 1-propanol
DK3160234T3 (da) 2014-06-27 2021-11-08 Kane Biotech Inc Sammensætning til anvendelse til forebyggelse og behandling af oftalmisk-, hånd- eller fodbiofilmvækst
US10370327B2 (en) 2014-07-02 2019-08-06 Board Of Regents, The University Of Texas System Ionic liquid films with multiple functionalities for surface modification of biomedical alloys
WO2016004321A1 (en) 2014-07-03 2016-01-07 Board Of Regents, The University Of Texas System Compounds for treating biofilm infection
US10023602B2 (en) 2014-07-08 2018-07-17 Universiteit Gent Hamamelitannin analogues and uses thereof
US9872893B2 (en) 2014-07-10 2018-01-23 University Of Maryland College Park Endolysins active against Staphylococcus bacteria, pharmaceutical compositions, and methods relating thereto
US10322082B2 (en) 2014-07-11 2019-06-18 Novan, Inc. Topical antiviral compositions and methods of using the same
EP3166959A4 (en) 2014-07-11 2017-12-13 C3 Jian, Inc. Targeting peptides that bind s. mutans, constructs comprising such peptides and uses thereof
BR112017000456B1 (pt) 2014-07-11 2022-12-13 Novan, Inc Uso de um ingrediente farmacêutico ativo de liberação de óxido nítrico e composição tópica para tratamento e/ou prevenção de uma infecção viral
US20160022595A1 (en) 2014-07-24 2016-01-28 Rhinotopic, LLC Bioadhesive and biodegradable and formulations that provide sustained release of antimicrobials, bacteriophages and anti-inflammatory medications for inactivation of biofilms and the treatment of rhinosinusitis and other infections
JP2017522122A (ja) 2014-07-24 2017-08-10 シノプシス サージカル インコーポレイテッドＳｉｎｏｐｓｙｓ Ｓｕｒｇｉｃａｌ，Ｉｎｃ． 副鼻腔アクセスインプラントデバイスおよび関連する製品ならびに方法
US20170202752A1 (en) 2014-07-25 2017-07-20 University Of Maryland, Baltimore Protein-repellent dental materials and use thereof in dental applications
US20160051569A1 (en) 2014-08-20 2016-02-25 Professional Compounding Centers Of America (Pcca) Methods for Inhibiting the Development, Formation and/or Maturation of Bacterial and Fungal Biofilms
EP2987408A1 (en) 2014-08-20 2016-02-24 National University of Ireland, Galway Iodophor composition with improved stability in the presence of organic material
EP3183002B1 (en) 2014-08-21 2021-03-03 Walter Reed Army Institute of Research Monoclonal antibodies for treatment of microbial infections
US9987200B2 (en) 2014-09-04 2018-06-05 Syact, Llp Activated micro-bubble based root canal disinfection
WO2016040785A1 (en) 2014-09-12 2016-03-17 K10 Technologies, Inc. Compositions and methods for treating and preventing bacterial infections
WO2016044683A1 (en) 2014-09-19 2016-03-24 Tensive Controls, Inc. Anti-microbial peptides
US20160106689A1 (en) 2014-09-22 2016-04-21 Novabiotics Limited Use
KR101741251B1 (ko) 2014-09-24 2017-06-12 한국해양과학기술원 Pseudoalteromonas arctica PAMC 21717 유래의 저온성 단백질분해효소 및 이의 용도
EP3200930B1 (en) 2014-09-30 2023-10-04 Luxembourg Institute of Science and Technology Plasma deposition method for catechol/quinone functionalised layers
WO2016051013A1 (en) 2014-10-02 2016-04-07 University Of Helsinki Abietane-type diterpenoids
CA2909044A1 (en) 2014-10-10 2016-04-10 Queen's University At Kingston Rhomboid proteins and uses thereof
US10023481B2 (en) 2014-10-17 2018-07-17 Clemson University Materials and methods for reducing biofouling in water treatment membrane systems
US10024817B2 (en) 2014-10-17 2018-07-17 Pelogenix, Llc Method for detecting proteases and active infection in biological fluids and tissues
US10905118B2 (en) 2014-10-24 2021-02-02 James Madison Innovations, Inc. Triscationic amphiphile compounds, compositions, and methods for making same
US10273440B2 (en) 2014-11-05 2019-04-30 Jeffry B. Skiba Devices and methods for creating and testing microbes and biofilms
EA038595B1 (ru) 2014-12-16 2021-09-21 Си3Джей ТЕРАПЬЮТИКС, ИНК. Композиции и способы для конструирования вирусного генома in vitro
KR20170096032A (ko) 2014-12-18 2017-08-23 에코랍 유에스에이 인코퍼레이티드 다가 알콜 폼에이트를 통한 퍼옥시폼산의 생성
US10118844B2 (en) 2014-12-31 2018-11-06 Ecolab Usa Inc. Multifunctional method for membrane protection and biofouling control
GB201501334D0 (en) 2015-01-27 2015-03-11 Medtrade Products Ltd Composition for a wound dressing
GB201501333D0 (en) 2015-01-27 2015-03-11 Medtrade Products Ltd Composition for a wound dressing
GB201501330D0 (en) 2015-01-27 2015-03-11 Medtrade Products Ltd Composition for a wound dressing
WO2016123539A1 (en) 2015-01-29 2016-08-04 Wardell Mark R Wound healing compositions involving medicinal honey, mineral ions, and methylglyoxal, and methods of use
WO2016127250A1 (en) 2015-02-09 2016-08-18 Ionescu Dan Andrei Method and system for delivery of particles in a root canal system
WO2016130554A1 (en) 2015-02-09 2016-08-18 Osinski Marek A Methods and compositions for antimicrobial treatment
WO2016130985A1 (en) 2015-02-13 2016-08-18 The Trustees Of The University Of Pennsylvania Iron oxide nanoparticles and methods of use thereof
US9326925B1 (en) 2015-02-26 2016-05-03 Johnson & Johnson Consumer Inc. Compositions comprising combinations of organic acids
AU2016222693B2 (en) 2015-02-26 2020-10-29 Johnson & Johnson Consumer Inc. Compositions comprising combinations of organic acids
US9326924B1 (en) 2015-02-26 2016-05-03 Johnson & Johnson Consumer Inc. Compositions comprising combinations of organic acids
US10745450B2 (en) 2015-02-27 2020-08-18 Fundació Centre De Regulació Genómica (Crg) Peptides and uses thereof
GB201503566D0 (en) 2015-03-03 2015-04-15 Spheritech Ltd Microparticles
GB201505184D0 (en) 2015-03-26 2015-05-13 Technion Res And Dev Company Ltd And Carmel Olefins Ltd Hollow mineral tubes comprising essential oils and uses thereof
US10087241B2 (en) 2015-03-26 2018-10-02 Regents Of The University Of Minnesota Polypeptdes, cells, and methods for biofilm therapy and detection
JP2018509994A (ja) 2015-03-27 2018-04-12 エリアス・セラピューティクス・インコーポレイテッドＥｌｉａｚ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 患者選択的アフェレシス
US20170035955A1 (en) 2015-03-27 2017-02-09 Eliaz Therapeutics, Inc. Apheresis based treatment for kidney disease
GB201505767D0 (en) 2015-04-02 2015-05-20 James Hutton Inst And Cellucomp Ltd Nanocomposite material
CN107820440A (zh) 2015-04-16 2018-03-20 Bsn医疗有限公司 一氧化氮（no）积聚装置
US20180085392A1 (en) 2015-04-17 2018-03-29 Sens Research Foundation, Inc. Cyclodextrin compounds for the prevention and treatment of aging
WO2016172436A1 (en) 2015-04-23 2016-10-27 Temple University-Of The Commonwealth System Of Higher Education Polycationic amphiphiles and polymers thereof as antimicrobial agents and methods using same
US9648876B2 (en) 2015-04-24 2017-05-16 Research Foundation Of City University Of New York Method of inhibiting biofilm formation
US20180125066A1 (en) 2015-04-26 2018-05-10 The Trustees Of Princeton University Surfaces comprising attached quorum sensing modulators
US20160319224A1 (en) 2015-04-29 2016-11-03 The Procter & Gamble Company Method of treating a fabric
WO2016176280A1 (en) 2015-04-29 2016-11-03 The Procter & Gamble Company Method of treating a fabric
DK3088505T3 (da) 2015-04-29 2020-08-03 Procter & Gamble Fremgangsmåde til behandling af et tekstilstof
EP3088504B1 (en) 2015-04-29 2021-07-21 The Procter & Gamble Company Method of treating a fabric
CN107820515A (zh) 2015-04-29 2018-03-20 宝洁公司 洗涤剂组合物
US20160324531A1 (en) 2015-05-05 2016-11-10 Rainbow Medical Ltd. Sinus treatment
US20160338993A1 (en) 2015-05-21 2016-11-24 The Regents Of The University Of California Wound healing
US10206906B2 (en) 2015-05-22 2019-02-19 The Royal Institution For The Advancement Of Learning/Mcgill University Synergistic combination of a phenolic-rich maple syrup extract and an antibiotic
US10557044B2 (en) 2015-06-24 2020-02-11 Wisconsin Alumni Research Foundation Slippery anti-fouling surfaces fabricated from reactive polymer multilayers
US10195241B2 (en) 2015-06-26 2019-02-05 Emory University Botanical extracts and compounds from Castanea plants and methods of use
BR112018000699B1 (pt) 2015-07-14 2023-10-17 Silk Therapeutics, Inc Artigo e método para revestir um material
US20180312473A1 (en) 2015-07-15 2018-11-01 Robert William Huigens, III Phenazine derivatives as antimicrobial agents
KR102258415B1 (ko) 2015-07-20 2021-05-28 쿼럼 이노베이션즈 엘엘씨 면역 반응 및 피부 및/또는 점막 장벽 기능을 개선하기 위한 물질 및 방법
US20180200185A1 (en) 2015-07-23 2018-07-19 Novaflux, Inc Implants and constructs including hollow fibers
US9556109B1 (en) 2015-07-31 2017-01-31 James Madison Innovations, Inc. Triscationic amphiphile derivative compounds having a pendent alcohol group, compositions thereof, and methods for making same
WO2017030966A1 (en) 2015-08-14 2017-02-23 Worcester Polytechnic Institute Anti-microbial coatings and devices
US10272126B2 (en) 2015-08-21 2019-04-30 The University Of Massachusetts Nanoparticle-stabilized microcapsules, dispersions comprising nanoparticle-stabilized microcapsules, and method for the treatment of bacterial biofilms
US10485902B2 (en) 2015-08-28 2019-11-26 Thomas Jefferson University Antibiotic drug release sheath
US20170064966A1 (en) 2015-09-08 2017-03-09 Bar Ilan University Antimicrobial compositions and methods and uses thereof
DE102015115958A1 (de) 2015-09-22 2017-03-23 Schott Ag Medizinisches Glaselement
US11008290B2 (en) 2015-09-24 2021-05-18 University Of Florida Research Foundation, Incorporated Halogenated quinoline derivatives as antimicrobial agents
US20170095502A1 (en) 2015-10-06 2017-04-06 Shantha Sarangapani Antimicrobial Metal-Binding Polymers
US20170100348A1 (en) 2015-10-12 2017-04-13 Microbiome Solutions, LLC Treatment Regime for Chronic Sinusitis
US10172362B2 (en) 2015-10-26 2019-01-08 The Penn State Research Foundation Biofilms, components and methods of use to reduce biofouling and contamination
WO2017075320A1 (en) 2015-10-31 2017-05-04 Dermalink Technologies, Inc. Skin adhesives, antimicrobial compositions, articles, and methods for the use thereof
GB201519923D0 (en) 2015-11-11 2015-12-23 Biovotec Dac And Biovotec As Dry biocompatible disintegrateable films for delivering particulate egg shell membrane to a wound
WO2017087895A1 (en) 2015-11-19 2017-05-26 Bloom Holdings, Llc Algae-derived flexible foam, and a method of manufacturing the same
US20190307726A1 (en) 2015-11-25 2019-10-10 Molecular Defenses Corporation Pharmaceutical formulations
GB201521238D0 (en) 2015-12-02 2016-01-13 Auspherix Ltd Anti-bacterial compounds
GB201521240D0 (en) 2015-12-02 2016-01-13 Auspherix Ltd Anti-bacterial compounds
CA3007778C (en) 2015-12-07 2023-09-26 Clean Chemistry, Inc. Methods of microbial control
WO2017109114A1 (en) 2015-12-23 2017-06-29 Diania Technologies Limited Thermoformed polymeric articles containing an additive
US20170182205A1 (en) 2015-12-28 2017-06-29 ProclaRx LLC Medical devices with biofilm disruptors
US20170183469A1 (en) 2015-12-28 2017-06-29 Bloom Holdings, Llc Algae-derived antimicrobial plastic substrates, and a method of manufacturing the same
US10301664B2 (en) 2015-12-31 2019-05-28 Purdue Research Foundation Repurposing non-antimicrobial drugs and clinical molecules to treat bacterial infections
EP3413942B1 (en) 2016-02-12 2023-01-11 Medical Components, Inc. Catheter locking solution and catheter locking therapy
US20170232048A1 (en) 2016-02-17 2017-08-17 Renuzoral Llc Adherent Dental Synbiotic Lozenge for Oral and General Health
US10226550B2 (en) 2016-03-11 2019-03-12 Brigham Young University Cationic steroidal antimicrobial compositions for the treatment of dermal tissue
EP3430125A4 (en) 2016-03-16 2020-03-25 Spogen Biotech Inc. FUSION PROTEINS, RECOMBINANT BACTERIA AND EXOSPORIUM FRAGMENTS FOR USE IN ANIMAL HEALTH AND AQUACULTURE
US20170273301A1 (en) 2016-03-24 2017-09-28 Keith Benson Hyperprotonation Compositions And Methods Of Use For Cleaning, Disinfection, And Sterilization
EP3436467A4 (en) 2016-03-30 2020-03-18 Ayuvis Research, Inc. NEW COMPOSITIONS AND THERAPEUTIC METHODS
CN109310722A (zh) 2016-04-01 2019-02-05 塔夫斯大学 用于预防弧菌感染的方法和组合物
US20200296971A1 (en) 2016-04-01 2020-09-24 Texas State University Compositions and methods for dispersing biofilms
JP2019518785A (ja) 2016-04-01 2019-07-04 デンツプライシロナ インコーポレイテッド バイオフィルム形成を阻害および妨害するための組成物および方法
US20170290789A1 (en) 2016-04-11 2017-10-12 Frank DiCosmo Wound irrigation solutions
US11446398B2 (en) 2016-04-11 2022-09-20 Obsidian Therapeutics, Inc. Regulated biocircuit systems
CA3020824C (en) 2016-04-15 2021-06-15 Ecolab Usa Inc. Performic acid biofilm prevention for industrial co2 scrubbers
MX2018013271A (es) 2016-05-02 2019-03-28 Paratek Pharm Innc Compuestos 9-aminometil minociclina y metodos para utilizarlos en el tratamiento de infeccion de vias urinarias (ivu).
WO2017195135A1 (en) 2016-05-11 2017-11-16 Nestec Sa Compositions and methods for reducing or preventing dental calculus accumulation in companion animals
KR20190017871A (ko) 2016-06-17 2019-02-20 칼리스타, 인코포레이티드 가스 공급 발효 반응기, 시스템 및 프로세스
CA3026166A1 (en) 2016-06-20 2017-12-28 Dentsply Sirona Inc. Three-dimensional fabricating material systems and methods for producing layered dental products
US11147746B2 (en) 2016-06-24 2021-10-19 Regents Of The University Of Minnesota Hydrophobic dental surfaces
US20180030403A1 (en) 2016-07-28 2018-02-01 Bobban Subhadra Devices, systems and methods for the production of humanized gut commensal microbiota
KR20240025050A (ko) 2016-07-29 2024-02-26 임베드 바이오사이언시스 아이엔씨. 상처 치유를 위한 방법 및 조성물
CA3032667C (en) 2016-07-31 2021-04-27 Sterilex, Llc Aluminum-compatible compositions for 2-part alkaline disinfectants and sanitizers
ES2833899T3 (es) 2016-08-10 2021-06-16 Adv Med Solutions Ltd Apósito para heridas
BR112019002366B1 (pt) 2016-08-11 2022-11-29 Colgate-Palmolive Company Composição para higiene bucal, método para fabricar a referida e método para tratar e/ou inibir mancha química, erosão dental, doença gengival, halitose e/ou formação de biofilme
US10144767B2 (en) 2016-08-18 2018-12-04 Board Of Regents Of The University Of Nebraska Anti-microbial peptides and coatings
GB201615047D0 (en) 2016-09-05 2016-10-19 Spheritech Ltd Microparticle composition and use thereof
US10266550B2 (en) 2016-09-16 2019-04-23 The Florida International University Board Of Trustees Bacterial topoisomerase I inhibitors with antibacterial activity
US10201518B2 (en) 2016-09-28 2019-02-12 The University Of Hong Kong Bismuth(III) compounds and methods thereof
CN110167955B (zh) 2016-09-29 2024-04-02 梅哈里医学院 细菌抑制剂
US10266793B2 (en) 2016-09-30 2019-04-23 Novaflux, Inc. Compositions for cleaning and decontamination
US11040037B2 (en) 2016-10-04 2021-06-22 Pop Test Oncology Llc Therapeutic agents and methods
US10293080B2 (en) 2016-10-05 2019-05-21 The Arizona Board Of Regents On Behalf Of Northern Arizona University Ionic liquids that sterilize and prevent biofilm formation in skin wound healing devices
CA3039062A1 (en) 2016-10-20 2018-04-26 Colgate-Palmolive Company Antimicrobial compositions for oral care or cleansing, and methods for anti-attachment polymers and coatings
US11111216B2 (en) 2016-10-26 2021-09-07 Temple University-Of The Commonwealth System Of Higher Education Polycationic amphiphiles as antimicrobial agents and methods using same
WO2018081740A1 (en) 2016-10-28 2018-05-03 The Regents Of The University Of California Tumescent antibiotic injection for treatment of chronic skin and soft tissue infections
US20200069777A1 (en) 2016-11-15 2020-03-05 Matoke Holdings Limited Antimicrobial compositions and formulations
KR102632424B1 (ko) 2016-11-30 2024-01-31 루브리졸 어드밴스드 머티어리얼스, 인코포레이티드 피부, 헤어, 네일 및/또는 점막의 치료 및/또는 케어를 위해 유용한 화합물
US11419335B2 (en) 2016-12-07 2022-08-23 University Of Florida Research Foundation, Incorporated N-arylated analogues and uses thereof
US20180184656A1 (en) 2017-01-05 2018-07-05 Cormedix Inc. Antimicrobial compositions, including antimicrobial hydrogels, effective against mature biofilms
RU2761409C2 (ru) 2017-01-10 2021-12-08 Калиста, Инк. Реакторы, системы и способы ферментации с подачей газа с применением зоны вертикального потока
US11053205B2 (en) 2017-02-17 2021-07-06 University Of Florida Research Foundation, Incorporated Phenazine derivatives as antimicrobial agents
AU2018249550B2 (en) 2017-04-05 2023-11-30 Curza, Inc. Compositions and methods comprising a triaryl polyamine
JP6821827B2 (ja) 2017-04-12 2021-01-27 ザ プロクター アンド ギャンブル カンパニーＴｈｅ Ｐｒｏｃｔｅｒ ＆ Ｇａｍｂｌｅ Ｃｏｍｐａｎｙ 布地柔軟剤組成物
EP3614842A4 (en) 2017-04-29 2021-02-24 Nevada Naturals, Inc. BIOFILM PENETRATING COMPOSITIONS AND PROCESSES
JP7210476B2 (ja) 2017-05-22 2023-01-23 インスメッド インコーポレイテッド リポ‐グリコペプチド可切断性誘導体及びその使用
EP3638274A1 (en) 2017-06-13 2020-04-22 Aobiome LLC Ammonia oxidizing microorganisms for dispersing biofilms
US20190008784A1 (en) 2017-07-07 2019-01-10 Symbiomix Therapeutics, Llc Novel secnidazole soft gelatin capsule formulations and uses thereof
EP3652318A1 (en) 2017-07-11 2020-05-20 Actym Therapeutics, Inc. Engineered immunostimulatory bacterial strains and uses thereof
TW201918252A (zh) 2017-07-18 2019-05-16 美商微辰生命有限公司 供使用及遞送至呼吸系統之微生物
CN111107919B (zh) 2017-08-14 2021-12-21 凯利斯塔公司 利用气/液分离容器的进气发酵反应器、系统和方法
US11390988B2 (en) 2017-09-27 2022-07-19 Evolved By Nature, Inc. Silk coated fabrics and products and methods of preparing the same
US20200306163A1 (en) 2017-09-27 2020-10-01 Evolved By Nature, Inc. Materials comprising recombinant silk and methods of preparing the same
US20190125825A1 (en) 2017-10-12 2019-05-02 High Point University Small-molecule adjuvants for antibiotics to address antibiotic resistance
US10835556B2 (en) 2018-02-28 2020-11-17 Board Of Trustees Of The University Of Illinois Hydrolyzed tetravalent metal salts and methods of biofilm inhibition
US11541105B2 (en) 2018-06-01 2023-01-03 The Research Foundation For The State University Of New York Compositions and methods for disrupting biofilm formation and maintenance
BR112021000315A2 (pt) 2018-07-11 2021-08-03 Actym Therapeutics, Inc. cepas bacterianas imunoestimulantes modificadas geneticamente e seus usos
WO2020047161A2 (en) 2018-08-28 2020-03-05 Actym Therapeutics, Inc. Engineered immunostimulatory bacterial strains and uses thereof
US11318149B2 (en) 2018-09-27 2022-05-03 Board Of Trustees Of Michigan State University Compositions and methods for inhibiting biofilm-forming bacteria
US20200121715A1 (en) 2018-10-20 2020-04-23 MC Technology Holdings, LLC Composition comprising aqueous medium with reduced size water clusters to improve bioavailability of the aqueous medium and methods for making and using the compositions
WO2020092802A1 (en) 2018-11-01 2020-05-07 The University Of Memphis Research Foundation Controlling biofilms with cyclopropanated fatty acids
US11167036B2 (en) 2018-11-27 2021-11-09 International Business Machines Corporation Techniques for enhancing the selectivity and efficacy of antimicrobial and anticancer polymer agents
US11698304B2 (en) 2019-02-15 2023-07-11 Wayne State University Apparatuses, systems, and methods for detecting materials based on Raman spectroscopy
US20200270613A1 (en) 2019-02-27 2020-08-27 Actym Therapeutics, Inc. Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment
SG11202108709PA (en) 2019-02-27 2021-09-29 The Fynder Group Inc Food materials comprising filamentous fungal particles and membrane bioreactor design
US11896612B2 (en) 2019-03-29 2024-02-13 Board Of Trustees Of Michigan State University Resurrection of antibiotics that MRSA resists by silver-doped bioactive glass-ceramic particles
US11224760B2 (en) 2019-04-16 2022-01-18 The Procter & Gamble Company Semisolid oral dispersions comprising bleaching agents
US11712408B2 (en) 2019-04-16 2023-08-01 The Procter & Gamble Company Semisolid oral dispersions comprising active agents
US10849729B2 (en) 2019-04-16 2020-12-01 The Procter & Gamble Company Multi-phase oral care compositions
US11559473B2 (en) 2019-04-16 2023-01-24 The Procter & Gamble Company Semisolid oral dispersions comprising active agents
US20200345585A1 (en) 2019-04-30 2020-11-05 Karl P. Dresdner, Jr. Process for making aqueous therapeutic particle having stable exterior water clustering with nanosized thickness
WO2020231786A1 (en) 2019-05-10 2020-11-19 Locus Ip Company, Llc Compositions and methods for treating biofilm-related lung conditions

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104056820A (zh) * 2014-05-12 2014-09-24 曹俊彪 耳鼻喉科用内镜消毒装置
CN104056820B (zh) * 2014-05-12 2016-03-09 曹俊彪 耳鼻喉科用内镜消毒装置
CN106390201A (zh) * 2016-09-21 2017-02-15 天津欧尔克医药科技有限公司 一种可吸收医用生物膜及其制备方法
CN110573192A (zh) * 2017-01-05 2019-12-13 科医公司 针对成熟生物膜有效的包括抗微生物水凝胶的抗微生物组合物
CN110229763A (zh) * 2019-04-30 2019-09-13 宁波大学 一株絮凝剂生产菌及其在对虾生物絮团养殖和染料脱色中应用
CN110229763B (zh) * 2019-04-30 2022-01-18 宁波大学 一株絮凝剂生产菌及其在对虾生物絮团养殖和染料脱色中应用
CN116903155A (zh) * 2023-09-13 2023-10-20 上海同济工程咨询有限公司 一种水质改良剂及其制备方法、水体养护方法
CN116903155B (zh) * 2023-09-13 2023-11-28 上海同济工程咨询有限公司 一种水质改良剂及其制备方法、水体养护方法

Also Published As

Publication number Publication date
US11452291B2 (en) 2022-09-27
BRPI0811530A2 (pt) 2014-11-18
JP5548121B2 (ja) 2014-07-16
US20200275653A1 (en) 2020-09-03
US8513305B2 (en) 2013-08-20
CA2684150C (en) 2016-10-04
US10653140B2 (en) 2020-05-19
GB2463181A (en) 2010-03-10
JP2010529952A (ja) 2010-09-02
GB0920909D0 (en) 2010-01-13
DE112008001301T5 (de) 2010-04-29
WO2008143889A1 (en) 2008-11-27
CA2684150A1 (en) 2008-11-27
US20080317815A1 (en) 2008-12-25
BRPI0811530B1 (pt) 2019-01-02
US20130302390A1 (en) 2013-11-14
CN101801521B (zh) 2015-06-17
DK200970201A (en) 2009-11-11
GB2463181B (en) 2013-03-27

Similar Documents

Publication Publication Date Title
CN101801521B (zh) 生物膜中细菌细胞内的生理学分散响应诱导
Lee et al. Anti-cariogenic effect of a cetylpyridinium chloride-containing nanoemulsion
CN104135856A (zh) 杀菌剂组合物
CN105916486A (zh) 含有羧酸的益生元口腔护理组合物
Nelson-Filho et al. Effect of triclosan dentifrice on toothbrush contamination
CN106029062A (zh) 用于破坏生物膜稳定性、改变生物膜和分散生物膜的组合物和方法
Liaqat et al. Biofilm, dental unit water line and its control
US20130216637A1 (en) Induction of a physiological dispersion response in bacterial cells in a biofilm
US20220211906A1 (en) Method for coating a medical device and coated medical device
CN109700751A (zh) 一种抑菌牙膏及其制备方法
CN104606085B (zh) 一种抗菌的醋酸洗必泰纳米乳漱口液及其制备方法
CN102234622B (zh) 改善口腔内细菌群的发酵乳酸杆菌sg-a95及其保健组合物
CN110478265A (zh) 一种生物活性物质植酸氨钠及其在口腔护理产品中的应用
Schlafer et al. Calcium-phosphate-osteopontin particles for caries control
Kim et al. Chamaecyparis obtusa suppresses virulence genes in Streptococcus mutans
Khudhair et al. Preparation and Evaluation of the Effectiveness of Mouthwash Prepared from Few Types of Plant Extracts against Some Types of Pathogenic Bacteria Isolated from Mouth
CN116836240A (zh) 益生菌以及抗菌肽在制备口腔组合物中的用途
CN116831970A (zh) 一种含有益生菌以及抗菌肽的口腔组合物
Poluan et al. The effectiveness test of 0.9 m nacl solution and 0.2% chlorhexidine gluconate on bacterial growth in the oral cavity of students batch 2018 at medical faculty, Universitas Kristen Indonesia
Murdiyanto et al. Tootpaste Formulation of Telang Flower (Clitoria Ternatea L.) Ethanol Extract as an Antibacterial for Streptococcus Mutans and Antifungal for Candida Albicans in the Oral Cavity
El Magrahi et al. Efficacy and effect of Salvadora persica (Miswak), Toothbrush and Toothpaste on colonization of Oral Microbial Flora
Rapiuddin et al. DEVELOPMENT OF TOOTHPASTE FORMULATION MODEL OF MANALAGI APPLE PEEL EXTRACT (Malus Sylvetris) WITH DIFFERENT CONCENTRATIONS AGAINST THE GROWTH OF STREPTOCOCCUS BACTERIA MUTANS IN VITRO AND IN VIVO
Tua-Ngam et al. Evaluation of Newly Formulated Chlorhexidine Mouthwash
Al-Hilu et al. Antibacterial efficacy against Streptococcus mutans and lactobacillus acidophilus in fluoride-containing pastes available in the market
Mohamad In vitro investigations into the antimicrobial and microecological effects of selected anti-plaque agents

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant