WO2001089595A1 - Surface polymere aux proprietes biologiquement actives et procedes permettant de la produire - Google Patents

Surface polymere aux proprietes biologiquement actives et procedes permettant de la produire Download PDF

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Publication number
WO2001089595A1
WO2001089595A1 PCT/DE2001/001951 DE0101951W WO0189595A1 WO 2001089595 A1 WO2001089595 A1 WO 2001089595A1 DE 0101951 W DE0101951 W DE 0101951W WO 0189595 A1 WO0189595 A1 WO 0189595A1
Authority
WO
WIPO (PCT)
Prior art keywords
biologically active
polymer surface
properties according
particles
active properties
Prior art date
Application number
PCT/DE2001/001951
Other languages
German (de)
English (en)
Inventor
Dieter Lohmann
Joachim Teller
Wolfgang SCHÜTT
Horst Klinkmann
Original Assignee
Research & Development Center Of Bioengineering Gmbh
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
Application filed by Research & Development Center Of Bioengineering Gmbh filed Critical Research & Development Center Of Bioengineering Gmbh
Publication of WO2001089595A1 publication Critical patent/WO2001089595A1/fr

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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
    • 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
    • A61L29/14—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
    • 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
    • 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
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/622—Microcapsules
    • 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
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/624—Nanocapsules
    • 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
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/626—Liposomes, micelles, vesicles

Definitions

  • Silver compounds have only limited success in reducing the adhesion and colonization of bacteria.
  • JP 10 015 042 (Tokyo Kogyo KK, 1996)
  • JP 10 211 272 (Unitika, 1997)
  • JP 10248919 (Unitika, 1997)
  • JP 08 117 326 (Unitika, 1996)
  • the disadvantages of the known processes and technical solutions are:
  • the active substances are not released uniformly.
  • the timing of the drug release is not controllable.
  • the release of active substances from a mixture cannot be controlled.
  • the drug release cannot be influenced from the outside.
  • the invention was therefore based on the object of carrying out such a modification of a polymer surface to be used in vivo which avoids the disadvantages described.
  • small particles for example nanocapsules, microcapsules or liposomes, which contain biologically active substances
  • the biologically active substances are released from these fixed particles in a controllable manner after the medical technology materials equipped with them have been introduced into the body.
  • Mixtures of these particles, which release the biologically active substances over different times, can also be used, so that it is possible to achieve the required almost uniform active concentrations on the surface of the implanted or introduced biomaterials over a long period of time.
  • Mixtures can also be used These particles, each containing different biologically active substances with different chemical and physical properties and resulting different release kinetics, are used, so that it is possible to set the different active concentrations for the different biologically active substances on the surface of the medical materials.
  • nano- or microcapsules or liposomes with defined release behavior are produced with known substances.
  • the active substance-containing particles produced in this way are bound to the polymer surface by means of bifunctional spacer groups.
  • the selection of these spacer groups depends on the chemical properties of the polymer to be modified on the one hand and the particles to be fixed on the other hand and the medium in which the coupling takes place.
  • Spacers containing isocyanate, isothiocyanate, epoxy and amino groups and carboxylic acid derivatives are particularly suitable.
  • spacers both chemical structures with predominantly hydrophobic or extremely hydrophilic properties can be considered.
  • Spacer groups consisting of polyalkylene glycol derivatives, in particular of polyethylene glycol derivatives or their block polymers with polypropylene glycol units, have proven useful for a number of applications.
  • the biologically active substances selected for medical use are e.g. antimicrobial substances, hormonally active substances, immunologically active substances, e.g. counteract the rejection of implants, substances that influence tumor growth, substances that prevent or prevent the deposition of the body's own molecules, substances that influence blood coagulation, or mixtures of the listed substances.
  • the particles can be heated in a targeted manner by an external electromagnetic alternating field. Due to the higher permeability of the capsule wall of the particles, a defined release of the biologically active substances can be achieved.
  • the advantages of the invention are that by the choice of encapsulation materials and modification of its chemical properties, the time course of the Drug release can be designed to be controllable, and that when using particle mixtures with different, previously defined, defined release behavior of the individual particle types, active substance activities can be achieved over longer periods of time, preferably in weeks, at the desired location of the catheter position in the patient.
  • a further advantage is that, depending on the medical necessity, the individual types of particles of a particle mixture fixed on the polymer surface contain different biologically active substances and can be released with a corresponding time characteristic.
  • the advantage of the invention is also that the use of particles which contain magnetic domains gives the possibility of releasing the encapsulated biologically active substance or mixture thereof at a freely selectable point in time after insertion or implantation of the medical device in the patient to cause.
  • This advantage can be used, for example, in the case of suddenly occurring infections or defense reactions or when a staggered release of active substance is required.
  • a section of polyurethane (PUR) tube with a length of 4 cm is swirled with 4 ml of hexamethylene diisocyanate / petroleum ether (1: 4) for three days at room temperature and washed once with 4 ml of n-hexane.
  • PUR polyurethane
  • the polyurethane surface is modified analogously to Example 1.
  • the particles are coated with polymethacrylic acid.
  • 600 mg of the particles obtained are resuspended in 25 ml of water.
  • the suspension is rotated in a rotary evaporator for 1 hour.
  • 120 ul methacrylic acid, 12 ul ethylene glycol dimethacrylate and 24 mg potassium peroxydisulfate are added.
  • the surface coating takes place while rotating at 65 ° C overnight.
  • the particles are resuspended in 10 ml of water.
  • a section of PUR tube with a length of 4 cm is swirled with 4 ml of hexamethylene diisocyanate / petroleum ether (1: 4) for three days at room temperature, washed once with 4 ml / 7-hexane and dried in vacuo at room temperature for 3 hours.
  • the PUR hose section is then swung with 4 ml of water overnight at room temperature (gas evolution) and washed once with 10 ml of water.
  • the incubation with water is repeated two more times and the PUR tube section is then dried in vacuo at room temperature for 3 hours.
  • the tube section is reacted with 4 ml of polyethylene glycol diglycidyl ether / petroleum ether (1: 4) while swirling overnight and washed once with 4 ml of n-hexane.
  • the functionalized tube section is swirled in 4 ml of petroleum ether, which contains 100 mg of rifampizine-PLA microcapsules, at room temperature overnight.
  • the tube section is washed once with 4 ml of n-hexane and dried in vacuo at room temperature for 3 hours.
  • the polyurethane surface is modified analogously to Example 1.
  • the functionalized tube section is swirled in 4 ml of petroleum ether, which contains 100 mg of rifampizine-PLA microcapsules, at room temperature overnight.
  • the tube section is washed once with 4 ml of n-hexane and dried in vacuo at room temperature for 3 hours.
  • the immobilized PLA microcapsules show a continuous release of active ingredient upon incubation in the plasma of approximately 130 ⁇ g active ingredient from 50 mg capsule material.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne des surfaces polymères aux propriétés biologiquement actives et des procédés permettant de les produire. De petites particules, par exemple des nanocapsules, des microcapsules ou des liposomes contenant des substances biologiquement actives sont fixées chimiquement à la surface polymère. Selon le domaine d'application, les substances biologiquement actives sont libérées de ces particules fixées, de manière régulée, après introduction des instruments médicaux ainsi équipés dans le corps. Il est également possible d'utiliser des mélanges de ces particules qui libèrent les substances biologiquement actives sur différentes périodes, de manière à parvenir, sur une longue période, à atteindre les concentrations en principe actif requises approximativement homogènes, à la surface des instruments médicaux. Il est également possible d'utiliser des mélanges de ces particules, qui contiennent dans chaque cas différentes substances biologiquement actives, aux diverses propriétés chimiques et physiques et les différentes cinétiques de libération qui en résultent, de manière à ajuster également les différentes concentrations en principe actif pour les substances biologiquement actives à la surface des instruments médicaux.
PCT/DE2001/001951 2000-05-24 2001-05-22 Surface polymere aux proprietes biologiquement actives et procedes permettant de la produire WO2001089595A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10025803.4 2000-05-24
DE2000125803 DE10025803A1 (de) 2000-05-24 2000-05-24 Polymeroberfläche mit biologisch aktiven Eigenschaften und Verfahren zu ihrer Herstellung

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WO2001089595A1 true WO2001089595A1 (fr) 2001-11-29

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DE (1) DE10025803A1 (fr)
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002074355A1 (fr) * 2001-03-15 2002-09-26 Dot Gmbh Materiaux a base de phosphate de calcium contenant des substances actives
WO2003030879A1 (fr) * 2001-10-05 2003-04-17 Surmodics, Inc. Revetement a particules immobilisees et leur utilisation
US7638344B2 (en) 2006-06-28 2009-12-29 Surmodics, Inc. Active agent eluting matrices with particulates
US8663674B2 (en) 2006-01-13 2014-03-04 Surmodics, Inc. Microparticle containing matrices for drug delivery
CN104740690A (zh) * 2015-04-03 2015-07-01 青岛明药堂医疗股份有限公司 一种海洋生物载药纳米抗菌超滑涂层
CN107789675A (zh) * 2017-10-31 2018-03-13 无锡中科光远生物材料有限公司 一种用于减轻植入材料异物反应的多重药物纤维膜的制备方法
CN112089892A (zh) * 2020-08-13 2020-12-18 四川大学 一种仿生改性的瓣膜材料及其制备方法和应用
CN112875955A (zh) * 2021-04-29 2021-06-01 山东沃华远达环境科技股份有限公司 一种医疗污水整合处理反应槽

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995003356A1 (fr) * 1993-07-23 1995-02-02 Massachusetts Institute Of Technology Nanoparticules et microparticules de copolymeres multibloc hydrophiles-hydrophobes non lineaires
WO1995020381A1 (fr) * 1994-01-28 1995-08-03 Fidia Advanced Biopolymers S.R.L. Revetement d'objets biomedicaux au moyen de microspheres composees de polymeres biocompatibles
WO1997047254A1 (fr) * 1996-06-12 1997-12-18 The Regents Of The University Of Michigan Compositions et procedes d'enrobage de dispositifs medicaux
US5718921A (en) * 1987-03-13 1998-02-17 Massachusetts Institute Of Technology Microspheres comprising polymer and drug dispersed there within
WO1998046287A2 (fr) * 1997-04-15 1998-10-22 Uroteq Inc. Administration de medicaments par l'intermediaire d'hydrogels therapeutiques
WO1999059556A1 (fr) * 1998-05-15 1999-11-25 Nasa/Johnson Space Center Microcapsules a declenchement exterieur
EP1080738A1 (fr) * 1999-08-05 2001-03-07 SORIN BIOMEDICA CARDIO S.p.A. Stent pour angioplastie

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5718921A (en) * 1987-03-13 1998-02-17 Massachusetts Institute Of Technology Microspheres comprising polymer and drug dispersed there within
WO1995003356A1 (fr) * 1993-07-23 1995-02-02 Massachusetts Institute Of Technology Nanoparticules et microparticules de copolymeres multibloc hydrophiles-hydrophobes non lineaires
WO1995020381A1 (fr) * 1994-01-28 1995-08-03 Fidia Advanced Biopolymers S.R.L. Revetement d'objets biomedicaux au moyen de microspheres composees de polymeres biocompatibles
WO1997047254A1 (fr) * 1996-06-12 1997-12-18 The Regents Of The University Of Michigan Compositions et procedes d'enrobage de dispositifs medicaux
WO1998046287A2 (fr) * 1997-04-15 1998-10-22 Uroteq Inc. Administration de medicaments par l'intermediaire d'hydrogels therapeutiques
WO1999059556A1 (fr) * 1998-05-15 1999-11-25 Nasa/Johnson Space Center Microcapsules a declenchement exterieur
EP1080738A1 (fr) * 1999-08-05 2001-03-07 SORIN BIOMEDICA CARDIO S.p.A. Stent pour angioplastie

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002074355A1 (fr) * 2001-03-15 2002-09-26 Dot Gmbh Materiaux a base de phosphate de calcium contenant des substances actives
US8679454B2 (en) 2001-10-05 2014-03-25 Surmodics, Inc. Particle immobilized coatings and uses thereof
US8158106B2 (en) 2001-10-05 2012-04-17 Surmodics, Inc. Particle immobilized coatings and uses thereof
WO2003030879A1 (fr) * 2001-10-05 2003-04-17 Surmodics, Inc. Revetement a particules immobilisees et leur utilisation
US8663674B2 (en) 2006-01-13 2014-03-04 Surmodics, Inc. Microparticle containing matrices for drug delivery
US7638344B2 (en) 2006-06-28 2009-12-29 Surmodics, Inc. Active agent eluting matrices with particulates
US8241921B2 (en) 2006-06-28 2012-08-14 Surmodics, Inc. Active agent eluting matrices with particulates
CN104740690A (zh) * 2015-04-03 2015-07-01 青岛明药堂医疗股份有限公司 一种海洋生物载药纳米抗菌超滑涂层
CN107789675A (zh) * 2017-10-31 2018-03-13 无锡中科光远生物材料有限公司 一种用于减轻植入材料异物反应的多重药物纤维膜的制备方法
CN112089892A (zh) * 2020-08-13 2020-12-18 四川大学 一种仿生改性的瓣膜材料及其制备方法和应用
CN112089892B (zh) * 2020-08-13 2021-08-31 四川大学 一种仿生改性的瓣膜材料及其制备方法和应用
CN112875955A (zh) * 2021-04-29 2021-06-01 山东沃华远达环境科技股份有限公司 一种医疗污水整合处理反应槽
CN112875955B (zh) * 2021-04-29 2021-07-16 山东沃华远达环境科技股份有限公司 一种医疗污水整合处理反应槽

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