CN1192057C - 抗菌素-聚合物复合物 - Google Patents
抗菌素-聚合物复合物 Download PDFInfo
- Publication number
- CN1192057C CN1192057C CNB021080313A CN02108031A CN1192057C CN 1192057 C CN1192057 C CN 1192057C CN B021080313 A CNB021080313 A CN B021080313A CN 02108031 A CN02108031 A CN 02108031A CN 1192057 C CN1192057 C CN 1192057C
- Authority
- CN
- China
- Prior art keywords
- antibiotics
- antibiotic
- application
- ketone
- described mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
Abstract
本发明涉及一种在生理条件下保证连续释放抗菌素数天时间并可用于人类医学及兽医学的抗菌素-聚合物复合物。本发明抗菌素-聚合物复合物的特征在于,在一种由一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯、甲基丙烯酸酯-丙烯酸酯共聚物这类疏水聚合物和一种或多种选自聚醚这类亲水聚合物组成的聚合物均匀混合物中,悬浮一种或者多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素、喹诺酮类抗菌素这类水难溶抗菌素,一种视需要择用并选自氨基甙类抗菌素、林可酰胺类抗菌素、β-内酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及视需要择用的一种有机辅助材料,并使该悬浮液形成一种复合物。
Description
技术领域
本发明涉及一种在生理条件下保证连续释放抗菌素数天时间并可用于人类医学及兽医学的抗菌素-聚合物复合物。
背景技术
人类医学及兽医学领域中,人们将引流管、导尿管、覆膜及网纱形式的塑料医用产品作为临时或者耐久植入物,以便进行分泌物吸出、冲洗、敷覆及固定。但这里的问题是,微生物尤其会通过导液管和导尿管的塑料软管进入机体,从而引起局部的感染,进而继续侵袭机体。在体外使用固定夹时也会出现类似的问题。这时微生物可以相同的方式沿着销接件进入机体。对于齿科植入物而言,植入表面出现感染的问题也已是不争的事实。所以就有必要在使用这些医用植入物时,对感染进行预防或进行消炎。从原则上讲,消炎需用适当的抗菌素进行全身或局部消炎。全身用抗菌素会出现一系列问题。为能全身达到抗微生物有效的抗菌素浓度,就要求用较高的抗菌素剂量。这样尤其对氨基甙类抗菌素和四环素类的抗菌素,由于其对肾或耳的毒性,常会引起不希望的伤害。所以通过局部采用抗菌素来消炎更好些,因为它能达到局部抗菌素有效浓度,而避免了很高的全身抗菌素浓度。
抗菌聚合物复合物的制备和使用,多年来一直是许多专利研究的目标。Shepherd和Gould就公布了用亲水的聚甲基丙烯酸酯和聚丙烯酸酯来涂覆导尿管,在该专利中未详细规定用抗菌素来治疗感染(T.H.Shepherd、F.E.Gould:导管,1971年3月3日,US 3566874)。Shepherd和Gould同样还在七十年代,根据亲水的羟基丙烯酸酯和羟基甲基丙烯酸酯聚合成抗菌模制体的原理,提出了抑制系。(T.H.Shepherd、F.E.Gould:干式亲水丙烯酸酯或甲基丙烯酸酯聚合延长释放药用植入物,1974年12月31日,US 3857932)。Klemm介绍了用聚甲基丙烯酸酯和聚丙烯酸酯制作的塑料粒子来治疗骨髓炎(K.Klemm:外科合成树脂材料和骨髓炎的治疗方法,1975年5月13日,US 3882858)。这种塑料粒子含有庆大霉素或另一种抗菌素。Gross等人对含有庆大霉素的骨粘固剂的制备提出了进一步的建议(A.Gross、R.Sch fer、S.Reiss:含有庆大霉素的骨粘固剂组合物,1977年11月22日,US 4059684),在此使用了水易溶的盐类作为辅料,如氯化钠、氯化钾、溴化钠和溴化钾加入到由甲基丙烯酸甲酯和丙烯酸甲酯、甲基丙烯酸甲酯、盐酸庆大霉素和/或硫酸庆大霉素的粉末共聚物组成的混合料中。以过氧化物使该混合料进行聚合。将骨粘固剂加入到生理环境后,水易溶的盐类便溶解并留出空隙。Batich等人根据使用的弱酸单体合成共聚物的原理,提出了一个新的释放系。这种单聚体从pH值8.5起开始溶涨,这样就能从封闭的药物有效成分中释放出生物活性物质(C.D.Batich、M.S.Cohen、K.Forster:活性成分受控释放的成分与设备,1996年10月10日,US 5554147)。
一系列其它研究工作的对象是将抗菌聚合物涂覆到医用品上。于是Conway等人便研究出一种硅酮聚合物基质,硝基呋喃基料中的水溶性生物活性物质细散地分布于其中(A.J.Conway、P.J.Conway、R.D.FryarJr.:持久释放的杀菌插管,1993年11月16日,US 5261896)。使用由聚氨酯、硅酮和可生物降解聚合物组成的一种基体聚合物,其中悬浮了一种由银盐和洗必太组成的混合物,用它来制作抗感染的医用品(C.L.FoxJr.、S.M.Modak、L.A.Sampath:消炎组合物、医疗器械和表面及其制备与使用方法,1991年5月28日,US 5019096)。Solomon、Byron和Parke根据聚氨酯和其中分散的洗必太,提出了一种类似的抗感染系统(D.D.Solomon、M.P.Byron:抗感染和抗血栓形成的医疗用品及其制备方法,1995年9月19日,US 5451424;D.D.Solomon、M.P.Parke:抗感染和抗血栓形成的医疗用品及其制备方法,1998年1月13口,US5707366;D.D.Solomon、M.P.Parke:抗感染和抗血栓形成的医疗用品及其制备方法,1998年1月13日,US 5165952)。这些系统可用熔液通过挤压制成模制体。同样也曾公布了由微量金属和聚合物组成的抗菌素组合物(D.Laurin,J.Stupar:抗微生物组合物,1984年7月29日,US 4603152)。建议将含有微量金属的ABS共聚物、聚氯乙烯、聚酯、聚氨酯、苯乙烯嵌段共聚物和橡胶作为聚合物用于抗感染。就是合成橡胶也能用于抗菌素。Allen就是这样通过向橡胶母料中添加活性成分便制作出高弹体-活性成分的组合物(D.L.Allen:含有治疗剂的弹性料组合物及其制成品,1991年5月28日,US 5019378)。母料的成分为橡胶、云母和二氧化钛。涂覆的抗菌素成分为分散到一种聚合物上的利福平和米诺四环素。Raad和Darouiche提出了如上提议(I.I.Raad、R.O.Darouiche:涂覆抗菌素的医用植入物,1993年6月8日,US 5217493)。该文未对聚合材料作详细阐述。De Leon等人公布了对植入物涂覆抗菌素的一种方法,先用硅油涂覆待涂表面(J.De Leon、T.H.Ferguson、D.S.Skinner Jr:涂覆有抗菌素的植入物的制作方法,1990年3月28日,US 4952419)。第二步,在硅油层上再涂粉状活性成分。这里将土霉素作为活性成分。Takigawa曾介绍了在硅油和聚(甲基丙烯酸酯)基质上的类似涂覆方法,从硅油和聚(甲基丙烯酸酯)的溶液延伸到松节油、N-癸烷、四氯甲烷、丁烷-2-酮、1,4-二恶烷和甲苯(B.Takigawa:含有硅油和聚甲基丙烯酸酯的涂覆溶液,1998年24日,US5721301)。Mustacich等人介绍了一种抗微生物的聚合物,将脂酸和脂酸盐作为抗微生物剂加到可医用的聚合物上(R.V.Mustacich、D.S.Lucas、R.L.Stone:抗微生物聚合成分,1984年10月30日,US 4479795)。Whitbourne和Mangan公布了一种令人感兴趣的涂覆组合物,将季铵化合物作为抗微生物的试剂涂到不溶于水的聚合物上,例如纤维素酯(R.J.Whitbourne、M.A.Mangan:含有药剂的涂覆组合物,1996年6月11日,US 5525348)。Friedmann等人介绍了一系列有关齿漆的专利(M.Firedmann、D.Steinerg、A.Soskolne:长久释放的药物组合物,1991年6月11日,US 5023082;M.Friedman、A.Sintov:液态聚合物组合物和使用方法,1992年11月3日,US 5160737;M.Friedman、A.Sintov:齿漆组合物和使用方法;1994年7月15日,US 5648399;M.Friedman、A.Sintov:齿漆组合物和使用方法;1997年6月17日,US 5639795)。这些专利在内容上大同小异,主要抗微生物物质是季铵盐。在专利中介绍了清漆和聚合物溶液的配制,其主要成分如下:一种由甲基丙烯酸和甲基丙烯酸酯所构成、具有游离羧酸基的共聚物、一种由甲基丙烯酸和甲基丙烯酸甲酯构成、具有游离羧酸基的共聚物、一种由二甲胺基乙基丙烯酸酯和乙基甲基丙烯酸酯构成的共聚物,以及一种由甲基丙烯酸酯和氯三甲基铵乙基甲基丙烯酸构成的共聚物。饶有兴趣的是US 5648399,它向聚合物中加入了影响材料释放的试剂,而这种试剂是由横向交联试剂、多聚糖、脂类化合物、多羟基化合物、聚碳酸、二价阳离子、柠檬酸、柠檬酸钠、二十二酸钠、蛋白质、聚氧乙烯去水山梨糖醇单油酯酯和铵酸基组成的。
Bayston和Grove提出了一种制作抗微生物医用品的建议(R.Bayston、N.J.Grove:抗微生物设备和方法,1990年4月17日,US4917686)。它将抗菌素物质溶解在一种适当的有机溶剂中。使这种溶液作用于待改性的聚合物表面。聚合物通过溶剂的浸泡而膨胀,活性成分可渗入表面。Darouche和Raad对导尿管和其它医疗植入物的抗微生物浸渍提出了一种在原理上相同的方法,它同样是将抗微生物的活性成分溶解在一种有机溶剂中(R.Darouche、I.Raad:抗微生物的浸渍导管与其它医用植入物以及对抗微生物剂导管和其它医用植入物的浸渍方法,1997年4月29日,US 5624704)。这些溶剂可作用于待治疗的表面,活性成分渗入材料中并在那儿沉积。
Lee记叙的用阳离子型抗菌素涂覆表面的方法,是迄今为止所记载的各种系统中一种可选用的方法(C.C.Lee:用阳离子抗菌素涂覆医疗器械,1990年1月23日,US 4895566)。这种方法是在需涂覆的表面涂一层荷负电的肝素,待粘合后再积聚阳离子抗菌素。Greco等人也提出了类似的溶液,先将阴离子型表面活性物质的溶液作用于涂覆表面(R.S.Greco、R.A.Harvey、S.Z.Trooskin:粘有药物的修复体与制作程序,1989年11月7日,US 4879135)。这时阴离子型分子吸附在表面上。然后,再静电接合阳离子型生物活性物质如庆大霉素。对后二种引用的方法都需注意,单位面积上抗菌素的涂覆密度极有限,这种涂层的粘接强度被视为是至关重要的。
发明内容
所要解决的技术问题
本发明所要解决的技术问题是研制出一种在生理条件下能在几天至几周时间中连续释放抗菌素并能用于人类医学和兽医学领域的柔性抗菌素-聚合物复合物。这种抗菌素-聚合物复合物能以简单的方式粘附于医用塑料和金属植入物的表面。尤其重要的是,涂层是柔软且富有弹性,不会排放有毒的成分。此外,这种柔性抗菌素-聚合物复合物也适合于制作抗菌素纱线、薄膜和模制体。
本发明令人信服的依据是:由一种或多种选自聚(甲基丙烯酸酯)、聚(丙烯酸酯)、甲基丙烯酸酯-丙烯酸酯共聚物的疏水聚合物和一种或多种聚醚类亲水聚合物所组成的均质聚合物混合物,其中悬浮一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素和喹诺酮类抗菌素基的水难溶抗菌素所形成的稳定的复合物,在含水环境中可持续释放抗菌素数日时间。下列说明是一种按下述设想所作的过程的说明性解释。在将复合物引入水性介质后,亲水性聚醚便溶解,进入溶液,而疏水的水不溶聚合物则保留下来。这样在剩下的疏水聚合基体中便产生了许多微孔、相互连通的空腔。也就是说在液态和生理条件下才产生作用,形成微孔、相互连通的空腔。在剩下的疏水聚合基体中,用物理方法封入水中不易溶解的抗菌素粒子。通过所形成的空腔,液体只有在形成后,才能达到水中不易溶解的抗菌素。在聚醚浸析时或浸析后才开始释放抗菌素。
这些亲水的聚合物在毒理学上是不予考虑的,其中的一些代表物已在欧洲药典上作了说明。这种抗菌素-聚合物复合物的优点特别是在于:悬浮于匀质聚合物混合液中的抗菌素在置于液态、生理条件下,是不会发生化学和机械作用的,例如磨损。只有在形成微孔互连的空腔后,抗菌素-聚合物复合物才会打开,释放出抗菌素。使用水难溶的抗菌素,使它极缓慢地从互连的空腔溶解。除此之外,匀质聚合混合物中的亲水聚醚组分也会影响到抗菌素的释放速度。
技术方案
本发明通过下列途径来完成这一任务:在一种由一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯、甲基丙烯酸酯-丙烯酸酯共聚物这类疏水聚合物和一种或多种选自聚醚这类亲水聚合物组成的聚合物均匀混合物中,悬浮一种或者多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素、喹诺酮类抗菌素这类微溶于水的抗菌素,一种视需要择用并选自氨基甙类抗菌素、林可酰胺类抗菌素、β-内酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及一种或者多种视需要择用的有机辅助材料,并使该悬浮液形成一种复合物。
下列实施方式已在实践中得到证实。
根据本发明,所述复合物由一种液态悬浮液经蒸发丙-2-酮和/或丁-2-酮而形成,所述悬浮液由一种丙-2-酮和/或丁-2-酮均匀混合物、一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯及甲基丙烯酸酯-丙烯酸酯共聚物的疏水聚合物和一种或多种选自聚醚的亲水聚合物组成,其中悬浮了一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素和喹诺酮类抗菌素的水微溶抗菌素,以及视需要择用的一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、β-内酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及视需要而择用的一种或多种有机辅料。
同样,根据本发明,所述复合物由一种熔融液形成,该熔融液由一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯及甲基丙烯酸酯-丙烯酸酯共聚物的疏水聚合物和一种或多种选自聚醚类的亲水聚合物组成,其中悬浮了其中悬浮了一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素和喹诺酮类抗菌素的水微溶抗菌素,视需要择用并选自一种选自氨基甙类抗菌素、林可酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及视需要而择用的一种或多种有机辅料。
此外,根据本发明,均匀聚合物混合物中,亲水性聚合物的含量为0.1至60%(重量)之间。
根据本发明,优选使用平均分子量在120gmol-1至35,000gmol-1范围之内的聚乙二醇作聚醚。
同样,根据本发明,优选使用平均分子量在200gmol-1至35,000gmol-1范围之内的聚丙二醇作聚醚。
根据本发明,优选使用平均分子量在200gmol-1至600gmol-1范围之内的聚乙二醇作聚醚。
根据本发明,优选采用平均分子量为20,000gmol-1至1,000,000gmol-1的聚(甲基丙烯酸甲酯)、聚(甲基丙烯酸乙酯)、聚(甲基丙烯酸丙酯)、聚(甲基丙烯酸正丁酯)、聚(甲基丙烯酸正己酯)、聚(甲基丙烯酸环己酯)、聚(丙烯酸甲酯)、聚(丙烯酸乙酯)、聚(丙烯酸丙酯)、聚(丙烯酸丁酯)及聚(丙烯酸环己酯)作疏水性聚合物。
还根据本发明,优选采用分子量为20,000gmol-1至1,000,000gmol-1的共聚物及三元共聚物作疏水聚合物,该疏水聚合物由丙烯酸甲酯、丙烯酸乙酯、丙烯酸丙酯、丙烯酸-正己酯、丙烯酸环己酯、甲基丙烯酸甲酯、甲基丙烯酸乙酯、甲基丙烯酸丙酯、甲基丙烯酸丁酯、甲基丙烯酸正己酯以及甲基丙烯酸环己酯制得。
根据本发明,优选采用使用磺胺药和/或消炎药和/或麻醉药和/或万古霉素作有机辅助材料。
根据本发明,所述可流动悬浮液在丙烷-2-酮和/或丁烷-2-酮蒸发条件下,纺成纱线状的复合物;
根据本发明,所述可流动悬浮液在丙-2-酮和/或丁-2-酮蒸发条件下,经浇铸制成箔片状复合物。
根据本发明,所述可流动悬浮液在丙-2-酮和/或丁-2-酮蒸发条件下,经喷雾法制成粉末以及颗粒状复合物。
根据本发明,所述复合物经由压制、挤压以及压延制成模制体及箔片。
根据本发明,用包覆以所述复合物的塑料软管、塑料纤维、塑料箔片、球形塑料形体物、圆筒形塑料形体物以及链状塑料形体物作医用植入物。
根据本发明,以所述复合物包覆导管、气管套管针头及腹膜内营养用软管。
根据本发明,以所述复合物包覆可植入的金属板、金属钉、金属螺钉。
此外,根据本发明,使用所述复合物来粘合医用塑料形体物、塑料箔片、塑料纱线、金属板以及金属管。
根据本发明,用所述复合物作粘合剂来制造由塑料颗粒、塑料粉末、可吸收玻璃粉、不可吸收玻玻璃粉末以及石英粉末制成的抗菌模制体。
根据本发明,所述可流动悬浮液经由浸涂、喷涂、刮涂、刷涂及辊涂,涂覆到塑料和/或金属表面上,并经蒸发丙-2-酮和/或丁-2-酮,制成一种覆层形式的复合物。
根据本发明,将所述复合物以覆层形式涂覆到医用塑料纱线、塑料箔片、塑料软管、塑料袋及塑料瓶上。
根据本发明,将所述复合物以覆层形式涂覆到由塑料和/或金属构成的球形模制体、圆筒形模制体及链状模制体上。
根据本发明,将所述复合物以覆层形式涂覆到由聚甲基丙烯酸酯、聚丙烯酸酯、甲基丙烯酸酯-丙烯酸酯共聚物、聚氯乙烯、聚偏二氯乙烯、聚硅氧烷、聚苯乙烯及聚碳酸酯制成的模制体、箔片及丝线上。
同样,根据本发明,也用所述复合物作粘合剂来制造抗菌层压制品。
此外,根据本发明,还将所述复合物经烧结以覆层形式涂覆到金属和/或塑料表面上。
具体实施方式
借助于下列三个实施例可以更详细地阐明本发明。
实施例1
制备一种由1.5g聚(甲基丙烯酸甲酯)、120mg聚乙二醇600及5ml丙酮组成的溶液。将300mg细粉状庆大霉素-五个-十六烷基磺酸盐及300mg庆大霉素硫酸盐悬浮于该溶液中。将该悬浮液倾倒在玻璃板上。令丙酮蒸发。与此同时产生一种半透明弹性薄膜,可从玻璃板上将其剥离下来。
实施例2
制备一种由1.5g聚(甲基丙烯酸甲酯)、120mg聚乙二醇600及5ml丙酮组成的溶液。将300mg细粉状庆大霉素-五个-十二烷基硫酸盐及300mg庆大霉素硫酸盐悬浮于该溶液中。将一段3厘米长的聚氯乙烯软管(管径4mm)浸入该悬浮液中。接着,令包覆过的聚氯乙烯软管在室温下干燥。在聚氯乙烯软管上得到一种粘附力强的弹性覆层。
实施例3
在一种由2g甲基丙烯酸-丙烯酸甲酯共聚物及200mg聚乙二醇600组成的熔融液(150℃)中,置入200mg细粉状庆大霉素-五个-十二烷基硫酸盐,并使之均匀分布。熔融液冷却后,得到一种乳白色不透明的固体复合物。
Claims (26)
1.抗菌素-聚合物复合物,其特征在于,所述复合物由一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯、甲基丙烯酸酯-丙烯酸酯共聚物的疏水聚合物和一种或多种选自聚乙二醇或聚丙二醇的聚醚亲水聚合物以及一种或者多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素、喹诺酮类抗菌素的微溶于水的抗菌素、任选的一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、β-内酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及任选的一种或者多种有机辅助材料所组成。
2.如权利要求1所述的抗菌素-聚合物复合物,其特征在于,在所述疏水聚合物和亲水聚合物的混合物中,亲水聚合物的重量含量在0.1至60%之间。
3.如权利要求1所述的抗菌素-聚合物复合物,其特征在于,聚乙二醇的平均分子量在120gmol-1至35000gmol-1范围之内。
4.如权利要求3所述的抗菌素-聚合物复合物,其特征在于,聚乙二醇的平均分子量在120gmol-1至600gmol-1范围之内。
5.如权利要求1所述的抗菌素-聚合物复合物,其特征在于,聚丙二醇的平均分子量在200gmol-1至35000gmol-1范围之内。
6.如权利要求1所述的抗菌素-聚合物复合物,其特征在于,所述疏水性聚合物选自平均分子量在20000gmol-1至1000000gmol-1范围之内的聚甲基丙烯酸甲酯、聚甲基丙烯酸乙酯、聚甲基丙烯酸丙酯、聚甲基丙烯酸正丁酯、聚甲基丙烯酸正己酯、聚甲基丙烯酸环己酯、聚丙烯酸甲酯、聚丙烯酸乙酯、聚丙烯酸丙酯、聚丙烯酸丁酯及聚丙烯酸环己酯。
7.如权利要求1所述的抗菌素-聚合物复合物,其特征在于,所述疏水性聚合物为分子量为20000gmol-1至1000000gmol-1的共聚物或三元共聚物,其由丙烯酸甲酯、丙烯酸乙酯、丙烯酸丙酯、丙烯酸正己酯、丙烯酸环己酯、甲基丙烯酸甲酯、甲基丙烯酸乙酯、甲基丙烯酸丙酯、甲基丙烯酸丁酯、甲基丙烯酸正己酯以及甲基丙烯酸环己酯制得。
8.如权利要求1所述的抗菌素-聚合物复合物,其特征在于,有机辅助材料为磺胺药和/或消炎药和/或麻醉药和/或万古霉素。
9.一种制备权利要求1-8中任意一项抗菌素-聚合物复合物的方法,其特征在于,所述复合物由一种液态悬浮液经蒸发丙-2-酮和/或丁-2-酮而形成,所述悬浮液由一种丙-2-酮和/或丁-2-酮均匀混合物、一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯及甲基丙烯酸酯-丙烯酸酯共聚物的疏水聚合物和一种或多种选自聚乙二醇或聚丙二醇的聚醚亲水聚合物组成,其中悬浮了一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素、喹诺酮类抗菌素的水微溶抗菌素,以及任选的一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、β-内酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及任选的一种或者多种有机辅料。
10.一种制备权利要求1-8中任意一项抗菌素-聚合物复合物的方法,其特征在于,所述复合物由一种熔融液形成,该熔融液由一种或多种选自聚甲基丙烯酸酯、聚丙烯酸酯及甲基丙烯酸酯-丙烯酸酯共聚物的疏水聚合物和一种或多种选自聚醚的亲水聚合物组成,其中悬浮了一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、四环素类抗菌素、喹诺酮类抗菌素的水微溶抗菌素,以及任选的一种或多种选自氨基甙类抗菌素、林可酰胺类抗菌素、β-内酰胺类抗菌素和四环素类抗菌素的水易溶抗菌素,以及任选的一种或者多种有机辅料。
11.如权利要求9所述的方法,其特征在于,所述悬浮液在丙-2-酮和/或丁-2-酮蒸发条件下,经由纺丝形成纱线形式的复合物。
12.如权利要求9所述的方法,其特征在于,所述悬浮液在丙-2-酮和/或丁-2-酮蒸发条件下,经浇铸制成箔片状复合物。
13.如权利要求9所述的方法,其特征在于,所述悬浮液在丙-2-酮和/或丁-2-酮蒸发条件下,经喷雾法制成粉末以及颗粒状复合物。
14.权利要求1-8中任意一项抗菌素-聚合物复合物作为医用植入物的应用。
15.如权利要求14所述的应用,其特征在于,所述的复合物为模制体及箔片。
16.如权利要求14所述的应用,其特征在于,将包覆所述复合物的塑料软管、塑料纤维、塑料箔片、球形塑料形体物、圆筒形塑料形体物以及链状塑料形体物作医用植入物。
17.如权利要求14所述的应用,其特征在于,以所述复合物包覆导管、气管套管针头及腹膜内营养用软管。
18.如权利要求14所述的应用,其特征在于,以所述复合物包覆可植入的金属板、金属钉、金属螺钉。
19.如权利要求14所述的应用,其特征在于,用所述复合物粘合医用塑料形体物、塑料箔片、塑料纱线、金属板以及金属管。
20.如权利要求14所述的应用,其特征在于,用所述复合物作粘合剂来制造由塑料颗粒、塑料粉末、可吸收玻璃粉、不可吸收玻璃粉、以及石英粉末制成的抗菌模制体。
21.如权利要求14所述的应用,其特征在于,用所述复合物作粘合剂来制造抗菌层压制品。
22.如权利要求14所述的应用,其特征在于,将所述复合物涂覆到塑料和/或金属表面上成为一种覆层形式的复合物。
23.如权利要求14所述的应用,其特征在于,将所述复合物以覆层形式涂覆到医用塑料纱线、塑料箔片、塑料软管、塑料袋及塑料瓶上。
24.如权利要求14所述的应用,其特征在于,将所述复合物以覆层形式涂覆到塑料和/或金属构成的球形模制体、圆筒形模制体及链状模制体上。
25.如权利要求14所述的应用,其特征在于,将所述复合物以覆层形式涂覆到由聚甲基丙烯酸酯、丙烯酸酯、甲基丙烯酸酯-丙烯酸酯共聚物、聚氯乙烯、聚偏二氯乙烯、聚硅氧烷、聚苯乙烯及聚碳酸酯制成的模制体、箔片及丝线上。
26.如权利要求14所述的应用,其特征在于,将所述复合物经烧结以覆层形式涂覆到金属和/或塑料表面上。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10114247.1 | 2001-03-22 | ||
DE10114247A DE10114247A1 (de) | 2001-03-22 | 2001-03-22 | Antibiotikum-/Antibiotika-Polymer-Kombination |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1376735A CN1376735A (zh) | 2002-10-30 |
CN1192057C true CN1192057C (zh) | 2005-03-09 |
Family
ID=7678694
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB021080313A Expired - Fee Related CN1192057C (zh) | 2001-03-22 | 2002-03-22 | 抗菌素-聚合物复合物 |
Country Status (32)
Country | Link |
---|---|
US (2) | US20020150549A1 (zh) |
EP (1) | EP1243259B1 (zh) |
JP (1) | JP3579676B2 (zh) |
CN (1) | CN1192057C (zh) |
AT (1) | ATE271857T1 (zh) |
AU (1) | AU772291B2 (zh) |
BG (1) | BG65475B1 (zh) |
BR (1) | BR0200879A (zh) |
CA (1) | CA2378487C (zh) |
CZ (1) | CZ2002867A3 (zh) |
DE (2) | DE10114247A1 (zh) |
DK (1) | DK1243259T3 (zh) |
EE (1) | EE200200154A (zh) |
ES (1) | ES2225670T3 (zh) |
GE (1) | GEP20053448B (zh) |
HR (1) | HRP20020241B1 (zh) |
HU (1) | HUP0201042A2 (zh) |
IL (1) | IL148704A (zh) |
IS (1) | IS2500B (zh) |
MD (1) | MD2380C2 (zh) |
MX (1) | MXPA02003005A (zh) |
NO (1) | NO20021388L (zh) |
NZ (1) | NZ517921A (zh) |
PL (1) | PL352921A1 (zh) |
PT (1) | PT1243259E (zh) |
RU (1) | RU2229896C2 (zh) |
SA (1) | SA02230034B1 (zh) |
SK (1) | SK286300B6 (zh) |
TR (1) | TR200402037T4 (zh) |
UA (1) | UA72271C2 (zh) |
YU (1) | YU18102A (zh) |
ZA (1) | ZA200202253B (zh) |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020163504A1 (en) * | 2001-03-13 | 2002-11-07 | Pallakoff Matthew G. | Hand-held device that supports fast text typing |
DE10261241A1 (de) * | 2002-12-20 | 2004-07-15 | 3M Espe Ag | Dentalmaterial mit bakteriostatischen und/oder bakteriziden Substanzen |
WO2004062588A2 (en) * | 2003-01-06 | 2004-07-29 | University Of Utah | Water-soluble polymeric bone-targeting drug delivery system |
WO2004075943A1 (en) | 2003-02-28 | 2004-09-10 | Biointeractions Ltd. | Polymeric network system for medical devices and methods of use |
US7279174B2 (en) * | 2003-05-08 | 2007-10-09 | Advanced Cardiovascular Systems, Inc. | Stent coatings comprising hydrophilic additives |
EP1646410B1 (en) * | 2003-07-17 | 2009-11-11 | Bioretec Oy | Synthetic, bioabsorbable polymer materials and implants |
AU2005325213B2 (en) | 2004-08-04 | 2010-10-07 | Evonik Corporation | Methods for manufacturing delivery devices and devices thereof |
US20070082029A1 (en) * | 2005-10-07 | 2007-04-12 | Aimutis William R | Fiber satiety compositions |
EP1787627A1 (en) * | 2005-11-17 | 2007-05-23 | 3M Innovative Properties Company | Anti-microbial dental impression material |
US11229746B2 (en) | 2006-06-22 | 2022-01-25 | Excelsior Medical Corporation | Antiseptic cap |
US9259535B2 (en) | 2006-06-22 | 2016-02-16 | Excelsior Medical Corporation | Antiseptic cap equipped syringe |
US8167847B2 (en) | 2006-06-22 | 2012-05-01 | Excelsior Medical Corporation | Antiseptic cap and antiseptic cap equipped plunger and syringe barrel assembly |
US9700710B2 (en) | 2006-06-22 | 2017-07-11 | Excelsior Medical Corporation | Antiseptic cap equipped syringe |
CA2743022C (en) * | 2007-01-21 | 2012-10-09 | Hemoteq Ag | Methods for coating catheter balloons with a defined quantity of active agent |
CN101636131B (zh) * | 2007-03-07 | 2012-03-14 | Med-El电气医疗器械有限公司 | 具有可移除磁铁的可植入装置 |
WO2008112592A1 (en) * | 2007-03-09 | 2008-09-18 | Anthem Orthopaedics Llc | Implantable medicament delivery device and delivery tool and method for use therewith |
US8124601B2 (en) * | 2007-11-21 | 2012-02-28 | Bristol-Myers Squibb Company | Compounds for the treatment of Hepatitis C |
ES2718612T3 (es) | 2007-12-20 | 2019-07-03 | Evonik Corp | Procedimiento para preparar micropartículas que tienen un bajo volumen de disolvente residual |
US9078992B2 (en) | 2008-10-27 | 2015-07-14 | Pursuit Vascular, Inc. | Medical device for applying antimicrobial to proximal end of catheter |
WO2010075298A2 (en) * | 2008-12-23 | 2010-07-01 | Surmodics Pharmaceuticals, Inc. | Implantable composites and compositions comprising releasable bioactive agents |
US20100215643A1 (en) * | 2009-02-25 | 2010-08-26 | Orthobond Corp. | Anti-infective functionalized surfaces and methods of making same |
US9114197B1 (en) | 2014-06-11 | 2015-08-25 | Silver Bullett Therapeutics, Inc. | Coatings for the controllable release of antimicrobial metal ions |
US8927004B1 (en) | 2014-06-11 | 2015-01-06 | Silver Bullet Therapeutics, Inc. | Bioabsorbable substrates and systems that controllably release antimicrobial metal ions |
US8221396B2 (en) | 2009-08-27 | 2012-07-17 | Silver Bullet Therapeutics, Inc. | Bone implants for the treatment of infection |
US9821094B2 (en) | 2014-06-11 | 2017-11-21 | Silver Bullet Therapeutics, Inc. | Coatings for the controllable release of antimicrobial metal ions |
US10265435B2 (en) | 2009-08-27 | 2019-04-23 | Silver Bullet Therapeutics, Inc. | Bone implant and systems and coatings for the controllable release of antimicrobial metal ions |
EP2637608B1 (en) | 2010-11-12 | 2016-03-02 | Silver Bullet Therapeutics Inc. | Bone implant and systems that controllably releases silver |
DE102011014386A1 (de) * | 2011-03-11 | 2012-09-13 | Hemoteq Ag | Endoprothese mit einer Wirkstoffbeschichtung |
WO2012162259A2 (en) | 2011-05-20 | 2012-11-29 | Excelsior Medical Corporation | Caps for cannula access devices |
US9867975B2 (en) * | 2011-05-23 | 2018-01-16 | Excelsior Medical Corporation | Antiseptic line cap |
US10166381B2 (en) | 2011-05-23 | 2019-01-01 | Excelsior Medical Corporation | Antiseptic cap |
EP2731658B1 (en) | 2011-07-12 | 2020-04-01 | Pursuit Vascular, Inc. | Device for delivery of antimicrobial agent into trans-dermal catheter |
US8834772B2 (en) | 2011-12-07 | 2014-09-16 | Biomet Manufacturing, Llc | Antimicrobial methacrylate cements |
CN103212087A (zh) * | 2013-04-19 | 2013-07-24 | 西北农林科技大学 | 抗生素-壳聚糖共价复合物及其制备方法和在制备抗肿瘤药物中的应用 |
ES2755352T3 (es) | 2014-05-02 | 2020-04-22 | Excelsior Medical Corp | Paquete en tira para tapón antiséptico |
US9452242B2 (en) | 2014-06-11 | 2016-09-27 | Silver Bullet Therapeutics, Inc. | Enhancement of antimicrobial silver, silver coatings, or silver platings |
CN104629279B (zh) * | 2015-02-03 | 2016-04-06 | 安徽民祯生物工程有限公司 | 一种细菌素抑菌保鲜生物复合膜 |
MD4399C1 (ro) * | 2015-02-19 | 2016-09-30 | Государственный Университет Молд0 | Material polimeric cu proprietăţi antibacteriene |
CA2982456A1 (en) | 2015-05-08 | 2016-11-17 | Icu Medical, Inc. | Medical connectors configured to receive emitters of therapeutic agents |
EP3984568A1 (en) | 2016-07-14 | 2022-04-20 | Hollister Incorporated | Hygienic medical devices having hydrophilic coatings and methods of forming the same |
SI3525865T1 (sl) | 2016-10-14 | 2023-01-31 | Icu Medical, Inc. | Razkuževalni pokrovčki za medicinske konektorje |
WO2018204206A2 (en) | 2017-05-01 | 2018-11-08 | Icu Medical, Inc. | Medical fluid connectors and methods for providing additives in medical fluid lines |
JP2021516075A (ja) * | 2018-01-31 | 2021-07-01 | ケラメッド インコーポレーテッド | 眼内インプラント用の抗微生物性ポリマ |
US11541221B2 (en) | 2018-11-07 | 2023-01-03 | Icu Medical, Inc. | Tubing set with antimicrobial properties |
US11400195B2 (en) | 2018-11-07 | 2022-08-02 | Icu Medical, Inc. | Peritoneal dialysis transfer set with antimicrobial properties |
US11541220B2 (en) | 2018-11-07 | 2023-01-03 | Icu Medical, Inc. | Needleless connector with antimicrobial properties |
US11517732B2 (en) | 2018-11-07 | 2022-12-06 | Icu Medical, Inc. | Syringe with antimicrobial properties |
US11534595B2 (en) | 2018-11-07 | 2022-12-27 | Icu Medical, Inc. | Device for delivering an antimicrobial composition into an infusion device |
CA3118905A1 (en) | 2018-11-21 | 2020-05-28 | Icu Medical, Inc. | Antimicrobial device comprising a cap with ring and insert |
CA3204371A1 (en) | 2020-12-07 | 2022-06-16 | Icu Medical, Inc. | Peritoneal dialysis caps, systems and methods |
CN114732019A (zh) * | 2022-05-09 | 2022-07-12 | 中国科学院城市环境研究所 | 一种组合物及应用和抑制或消杀金黄色葡萄球菌的方法 |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3566874A (en) * | 1968-08-13 | 1971-03-02 | Nat Patent Dev Corp | Catheter |
US3857932A (en) * | 1970-09-09 | 1974-12-31 | F Gould | Dry hydrophilic acrylate or methacrylate polymer prolonged release drug implants |
DE2320373B2 (de) * | 1973-04-21 | 1978-04-06 | Merck Patent Gmbh, 6100 Darmstadt | Antibioticahaltiges Mittel und seine Verwendung als chirurgisches Kunststoffmaterial |
DE2511122B2 (de) * | 1975-03-14 | 1977-06-08 | Vorprodukt fuer die zubereitung von knochenzement | |
DE2920500A1 (de) * | 1979-05-21 | 1980-11-27 | Boehringer Sohn Ingelheim | Pharmazeutische zubereitung in form eines polyacrylatfilmes |
US4479795A (en) * | 1979-06-29 | 1984-10-30 | The Procter & Gamble Company | Antimicrobial polymer compositions |
DE3204551A1 (de) * | 1982-02-10 | 1983-08-18 | Boehringer Ingelheim KG, 6507 Ingelheim | Verfahren zur herstellung einer pharmazeutischen zubereitung in form eines polyacrylat-films |
US4603152A (en) * | 1982-11-05 | 1986-07-29 | Baxter Travenol Laboratories, Inc. | Antimicrobial compositions |
US4917686A (en) * | 1985-12-16 | 1990-04-17 | Colorado Biomedical, Inc. | Antimicrobial device and method |
IL78826A (en) * | 1986-05-19 | 1991-05-12 | Yissum Res Dev Co | Precursor composition for the preparation of a biodegradable implant for the sustained release of an active material and such implants prepared therefrom |
US4846844A (en) * | 1987-08-31 | 1989-07-11 | Eli Lilly And Company | Antimicrobial coated implants |
US5019378A (en) * | 1987-12-29 | 1991-05-28 | Cuno, Incorporated | Elastomeric composition containing therapeutic agents and articles manufactured therefrom |
US5019096A (en) * | 1988-02-11 | 1991-05-28 | Trustees Of Columbia University In The City Of New York | Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same |
US5330746A (en) * | 1988-05-03 | 1994-07-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Dental varnish composition, and method of use |
US5438076A (en) * | 1988-05-03 | 1995-08-01 | Perio Products, Ltd. | Liquid polymer composition, and method of use |
US5160737A (en) * | 1988-05-03 | 1992-11-03 | Perio Products Ltd. | Liquid polymer composition, and method of use |
US5165952A (en) * | 1989-01-18 | 1992-11-24 | Becton, Dickinson And Company | Anti-infective and antithrombogenic medical articles and method for their preparation |
US5525348A (en) * | 1989-11-02 | 1996-06-11 | Sts Biopolymers, Inc. | Coating compositions comprising pharmaceutical agents |
US5261896A (en) * | 1990-01-10 | 1993-11-16 | Rochester Medical Corporation | Sustained release bactericidal cannula |
AU657514B2 (en) * | 1991-01-03 | 1995-03-16 | Glaxo Canada Inc. | Method for production of solid pharmaceutical preparation |
US5217493A (en) * | 1992-03-11 | 1993-06-08 | Board Of Regents, The University Of Texas System | Antibacterial coated medical implants |
US5554147A (en) * | 1994-02-01 | 1996-09-10 | Caphco, Inc. | Compositions and devices for controlled release of active ingredients |
JP3087105B2 (ja) * | 1995-04-20 | 2000-09-11 | 敏 瀧川 | シリコンオイルとポリメタアクリル酸アルキルエステルよりなる塗剤 |
WO1997006833A1 (en) * | 1995-08-11 | 1997-02-27 | Dendritech, Inc. | Hyper comb-branched polymer conjugates |
US5681289A (en) * | 1995-08-14 | 1997-10-28 | Medicinelodge Inc. | Chemical dispensing system |
US6110483A (en) * | 1997-06-23 | 2000-08-29 | Sts Biopolymers, Inc. | Adherent, flexible hydrogel and medicated coatings |
-
2001
- 2001-03-22 DE DE10114247A patent/DE10114247A1/de not_active Withdrawn
-
2002
- 2002-02-13 MD MDA20020072A patent/MD2380C2/ro not_active IP Right Cessation
- 2002-02-15 IS IS6272A patent/IS2500B/is unknown
- 2002-02-19 GE GE4859A patent/GEP20053448B/en unknown
- 2002-02-27 BG BG106455A patent/BG65475B1/bg unknown
- 2002-03-06 ES ES02004978T patent/ES2225670T3/es not_active Expired - Lifetime
- 2002-03-06 DE DE50200680T patent/DE50200680D1/de not_active Expired - Lifetime
- 2002-03-06 DK DK02004978T patent/DK1243259T3/da active
- 2002-03-06 PT PT02004978T patent/PT1243259E/pt unknown
- 2002-03-06 AT AT02004978T patent/ATE271857T1/de not_active IP Right Cessation
- 2002-03-06 EP EP02004978A patent/EP1243259B1/de not_active Expired - Lifetime
- 2002-03-06 TR TR2004/02037T patent/TR200402037T4/xx unknown
- 2002-03-08 CZ CZ2002867A patent/CZ2002867A3/cs unknown
- 2002-03-13 YU YU18102A patent/YU18102A/sh unknown
- 2002-03-14 IL IL148704A patent/IL148704A/en not_active IP Right Cessation
- 2002-03-18 SK SK390-2002A patent/SK286300B6/sk not_active IP Right Cessation
- 2002-03-19 US US10/100,865 patent/US20020150549A1/en not_active Abandoned
- 2002-03-19 JP JP2002076876A patent/JP3579676B2/ja not_active Expired - Fee Related
- 2002-03-20 MX MXPA02003005A patent/MXPA02003005A/es active IP Right Grant
- 2002-03-20 ZA ZA200202253A patent/ZA200202253B/xx unknown
- 2002-03-20 NO NO20021388A patent/NO20021388L/no not_active Application Discontinuation
- 2002-03-21 UA UA2002032262A patent/UA72271C2/uk unknown
- 2002-03-21 HR HR20020241A patent/HRP20020241B1/xx not_active IP Right Cessation
- 2002-03-21 HU HU0201042A patent/HUP0201042A2/hu unknown
- 2002-03-21 NZ NZ517921A patent/NZ517921A/en unknown
- 2002-03-21 AU AU27558/02A patent/AU772291B2/en not_active Ceased
- 2002-03-21 RU RU2002107209/15A patent/RU2229896C2/ru not_active IP Right Cessation
- 2002-03-21 BR BR0200879-3A patent/BR0200879A/pt not_active IP Right Cessation
- 2002-03-21 PL PL02352921A patent/PL352921A1/xx unknown
- 2002-03-22 CN CNB021080313A patent/CN1192057C/zh not_active Expired - Fee Related
- 2002-03-22 CA CA002378487A patent/CA2378487C/en not_active Expired - Fee Related
- 2002-03-22 EE EEP200200154A patent/EE200200154A/xx unknown
- 2002-04-02 SA SA02230034A patent/SA02230034B1/ar unknown
-
2007
- 2007-10-31 US US11/931,895 patent/US20080058733A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1192057C (zh) | 抗菌素-聚合物复合物 | |
Aggarwal et al. | Drug-loaded biomaterials for orthopedic applications: A review | |
CN102202700B (zh) | 聚合材料 | |
CA2438346C (en) | Polymer composite comprising a continuous release antibiotic | |
Carvalho et al. | Doxycycline release and antibacterial activity from PMMA/PEO electrospun fiber mats | |
WO1998007458A1 (en) | Surface coating method for metal implants | |
Wang et al. | 3D printing of multi-functional artificial conduits against acute thrombosis and clinical infection | |
Ning et al. | Recent developments in controlled release of antibiotics | |
US20080081060A1 (en) | Chitosan-coated calcium sulfate based medicament delivery system | |
Bračič et al. | Polysaccharides in medical applications | |
WO2018082722A1 (en) | Polymeric thermoplastic biodegradable composition for production of inserts for treatment and prevention of local infections and a method of preparation thereof | |
WO2009054854A1 (en) | Loadable polymeric particles for bone augmentation and methods of preparing and using the same | |
WO2023183872A1 (en) | Delmopinol and delmopinol salt containing nanoparticles and uses thereof | |
KR100402053B1 (ko) | 항생제의 서방성 임플란트 제제 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
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 | ||
C17 | Cessation of patent right | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20050309 Termination date: 20110322 |