WO2000072896A9 - Dispositif pour medication a revetement polymere superficiel de protection contre l'adhesion des proteines - Google Patents

Dispositif pour medication a revetement polymere superficiel de protection contre l'adhesion des proteines

Info

Publication number
WO2000072896A9
WO2000072896A9 PCT/US2000/014642 US0014642W WO0072896A9 WO 2000072896 A9 WO2000072896 A9 WO 2000072896A9 US 0014642 W US0014642 W US 0014642W WO 0072896 A9 WO0072896 A9 WO 0072896A9
Authority
WO
WIPO (PCT)
Prior art keywords
medical device
medication
hydrophilic
polymeric
polymeric material
Prior art date
Application number
PCT/US2000/014642
Other languages
English (en)
Other versions
WO2000072896A1 (fr
Inventor
Antwerp William P Van
Original Assignee
Minimed Inc
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 Minimed Inc filed Critical Minimed Inc
Priority to AU51682/00A priority Critical patent/AU5168200A/en
Publication of WO2000072896A1 publication Critical patent/WO2000072896A1/fr
Publication of WO2000072896A9 publication Critical patent/WO2000072896A9/fr

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
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/06—Use of 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
    • A61L29/08—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
    • 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

Definitions

  • This invention relates generally to reusable and disposable medical devices that are used to store, contain or deliver protein-based medications. More particularly, this invention relates to improved medical devices that have one or more protein-contacting surfaces treated to reduce the protein adsorption and denaturation that can occur on an untreated surface.
  • Medication infusion pumps are generally known in the art for use in delivering a selected medication to a patient in a preprogrammed or patient- programmed manner. In recent years, infusion pumps have been developed in
  • Medication infusion pumps have also been used to deliver a wide variety of other drugs to a patient.
  • Such medications or drugs include, for example, baclofen, morphine and other pain medications, various antibiotics, and a number of
  • medication contacting surfaces are typically constructed from materials, such as metals,
  • polymers or other materials that have low free surface energies, typically on the order of about 40 dyne/cm 2 .
  • protein-based medications can be adsorbed quite readily and can subsequently denature on the medication contacting surfaces. Once denaturing occurs, the protein-based substances can aggregate to a form that is generally not bio-available to the patient and may in some cases lead to undesired immunological response.
  • the present invention provides an improved medical device having a hydrophilic internal surface coating or coatings, resulting in device surfaces that are highly stable in the presence of complex protein-based medications.
  • a medical device having a non-metallic surface contacted by a selected protein- based medication.
  • the surface has a covalently attached surface treatment that defines a surface contact angle less than about 45 degrees, and also exhibits a protein adso ⁇ tion profile of less than about 1.0 microgram per square centimeter when measured with either albumin or insulin.
  • the medical device is a medication infusion pump.
  • the medication infusion pump can be reusable or disposable, and can be externally worn or implantable.
  • the medical device according to the invention is not limited to a medication infusion pump, however, but can also be a device such as a prefilled medication cartridge, a syringe, a catheter, an IV bag, and the like.
  • the non-metallic surface is a polymeric surface, such as a rubber, a polyurethane, a polyethylene, a polypropylene or a polyvinylchloride.
  • the polymeric surface is comprised of a bromobutyl rubber or a chlorobutyl rubber.
  • the surface treatment is a coating comprised of polymeric materials such as hydrophilic polyurethanes, polyureas, acrylics, polycarbonates or other hydrophilic materials, in particular materials such as polyethylene glycols, polyethylene/polypropylene glycol copolymers or other poloxamers which are chemically (covalently) attached to the treated surface.
  • polymeric materials such as hydrophilic polyurethanes, polyureas, acrylics, polycarbonates or other hydrophilic materials, in particular materials such as polyethylene glycols, polyethylene/polypropylene glycol copolymers or other poloxamers which are chemically (covalently) attached to the treated surface.
  • a medication infusion device for contacting a selected protein-based medication, the device having a non-metallic surface for contacting the medication.
  • the non-metallic surface has a coating to reduce the surface contact angle and protein adso ⁇ tion profile.
  • the non-metallic surface is a polymeric surface as set forth above, and the coating is a polymeric material as set forth above.
  • a component for use in a medication infusion device as described herein has a non-metallic surface having a covalently attached surface treatment that defines a surface contact angle less than about 45 degrees and exhibits a protein adso ⁇ tion profile of less than about 1.0 microgram per square centimeter when measured with albumin or insulin.
  • a method of treating a non-metallic surface for use in a medical device for contacting a selected protein-based medication includes the step of treating the non-metallic surface to produce a covalently attached surface treatment that defines a surface contact angle less than about 45 degrees and exhibits a protein adso ⁇ tion profile of less than about 1.0 microgram per centimeter when measured with albumin or insulin.
  • the non-metallic surface is a polymeric surface as set forth above, and the treating step includes the application of a coating of a polymeric material as set forth above to the polymeric surface.
  • the polymeric material is applied to the surface by dipping, spraying, pre-polymerization followed by polymeric attachment, RP-plasma attachment, grafting, or silane-based primer attachment, and subsequently cured, preferably by exposure to actinic radiation (e.g., UV radiation), free radicals, elevated temperature, RF energy, or by other chemical reactions. If needed, the application and curing steps are repeated to ensure that the entire surface is provided with the coating.
  • actinic radiation e.g., UV radiation
  • free radicals e.g., UV radiation
  • elevated temperature RF energy
  • FIG. 1 is side sectional view depicting a typical externally mountable infusion device
  • FIG. 2 is a side sectional perspective view, partially in phantom, of a medicament reservoir used with an infusion device.
  • the present invention is related to the subject matter of U.S. Patent Application Serial No. 08/742,377, filed November 1, 1996, which pertains in part to the treatment of metallic surfaces such as titanium.
  • the disclosure of the foregoing application is inco ⁇ orated in its entirety herein by reference.
  • a medication device includes one or more internal surfaces bearing a hydrophilic coating or otherwise treated to exhibit hydrophilic characteristics, which have been found to substantially reduce or eliminate accumulation of undesired medication deposits particularly when the medication device is used to deliver complex protein based medications such as insulin and the like.
  • the hydrophilic internal surfaces have been found to significantly reduce and/or eliminate undesired adso ⁇ tion of proteins on internal pump surfaces.
  • the invention can be applied to a wide range of different types of pumps, including both reusable and non-reusable pumps, as well as to both implantable and externally worn pumps.
  • the invention is applicable to an externally worn, gas powered infusion device as described in U.S. Patent No. 5,785,688; an implantable constant-flow medication infusion pump as described in U.S. Patent Application Serial No. 08/871,830; and the pumps described in U.S. Patent Application Serial No. 09/253,382 (attorney docket no. PD-0296) and Serial No. 09/253,383 (attorney docket no.
  • PD-0297 the disclosures of which are inco ⁇ orated herein in their entireties by reference, as well as other medical devices that employ flexible displaceable membranes.
  • These exemplary medical devices include flexible non-metallic internal membranes which separate medicament reservoirs from propellant reservoirs.
  • Such pumps can be driven by an elastomeric sponge surrounding the medicament reservoir (e.g., from Science Inco ⁇ orated); in which a propellant reservoir is prefilled with a gas or chemical solution to generate a gas (e.g., from River Medical); or in which a gas is generated electrochemically within the propellant reservoir (e.g., from Elan Co ⁇ oration or CeramTec, Inc.).
  • the invention can further be applied to a variety of pump surfaces including both metallic and non-metallic surfaces to reduce the surface contact angle for hydrophilic characteristics.
  • the invention is not limited to pumps, but is also suitable for application to any medical device having one or more components that are contacted by a selected protein-based medication.
  • medical devices include, without limitation, prefilled medication cartridges having internal pistons; polymeric syringe bodies, reservoirs, plungers and plunger O-rings; polymeric catheters; IV bags; polymeric bottles and other storage containers; or the like.
  • Additional exemplary medical devices include replaceable or disposable syringes or reservoirs for medication infusion pumps, such as those commercially available from MiniMed Inc. and Disetronic.
  • medication infusion pumps such as those commercially available from MiniMed Inc. and Disetronic.
  • U.S. Patent 4,373,527 and 4,573,994 both of which are inco ⁇ orated by reference herein.
  • U.S. Patents 4,568,520; 4,569,241; 4,636,150; and 4,714,234 all of which are inco ⁇ orated by reference herein.
  • the present invention relates to a medication device wherein one or more internal surfaces are coated to achieve a significant reduction in surface free energy.
  • an externally worn medication infusion pump 10 includes propellant reservoir 12 and medicament reservoir 14 separated by flexible non-metallic (e.g, polymeric) membrane 16.
  • Membrane 16 has a surface 18 in contact with the medicament in reservoir 14. Surface 18 is provided with a surface treatment according to the present invention.
  • the propellant reservoir 12 contains a gas generated electrochemically or chemically to apply pressure to the membrane 16 in order to expel the medicament from the medicament reservoir 14.
  • the medicament is delivered to the patient via catheter 20 and an infusion set 22 having cannula 24.
  • a prefilled medicament cartridge 30 for use with a medicament infusion pump includes a non-metallic piston 32 driven by plunger 34 into reservoir 36.
  • Piston 32 has a surface 38 which is treated according to the invention.
  • Reservoir 36 which can be formed from a non-metallic material such as glass, a polymer or the like, has a surface 40 which also can be treated according to the invention.
  • the medicament within reservoir 36 is supplied via orifice 42 into the medicament infusion pump (not shown) in which cartridge 30 has been inserted.
  • Non-metallic surfaces can be comprised, for example, of a polymeric material, for example a rubber such as bromobutyl rubber or chlorobutyl rubber, a polyurethane, a polyethylene, a polypropylene, a polyvinylchloride, or other similar polymeric materials.
  • a polymeric material for example a rubber such as bromobutyl rubber or chlorobutyl rubber, a polyurethane, a polyethylene, a polypropylene, a polyvinylchloride, or other similar polymeric materials.
  • the medical device components can be made of a polymeric material, such as those listed above, or can be formed from a polymer laminate (e.g., two or more layers of different polymeric materials) or a metallized polymeric material, in which case the polymeric material has a non-metallized surface which has a surface treatment according to the invention.
  • the surface treatment according to the invention can be, for example, a coating formed from a polymeric material.
  • Specific polymeric materials useful to provide a surface treatment according to the invention include, without limitation, materials such as hydrophilic polyurethanes, polyureas, acrylics, as well as other hydrophilic components.
  • Particular materials include polyethylene glycols, polyethylene/polypropylene glycol copolymers and other poloxamers. These coatings preferably are covalently bonded to the surface which is being treated.
  • One particular method for forming the coating includes the steps of adsorbing the polymeric material to the surface, and then covalently attaching the polymeric material to the surface by exposure to UV radiation, RF energy, heat, X-ray radiation, gamma radiation, electron beams, or the like. If needed, the foregoing application and curing steps are carried out at least twice, more particularly at least three times, in order to avoid bubble formation and provide uniform surface coverage.
  • Another particular method includes the step of covalently attaching a linker molecule to the surface.
  • Linker molecules that are useful in this embodiment of the inventive method include, without limitation, silanes of the formula SiX 3 -R, wherein X is a methyl group or a halogen atom such as chlorine and R is a functional group which can be a coating material as described herein or a group which is reactive with a coating material.
  • Particular silane-terminated compounds include vinyl silanes, silane-terminated acrylics, silane-terminated polyethylene glycols (PEGs), silane-terminated isocyanates and silane-terminated alcohols.
  • the silanes can be reacted with the surface by various means known to those skilled in the art.
  • dichloro methyl vinyl silane can be reacted with the surface in aqueous ethanol.
  • the linker molecule strongly binds to the surface via -O-Si bonds or directly with the silicon atom.
  • the vinyl group of the silane can then be reacted with polymeric materials as described herein using appropriate conventional chemistries.
  • a methacrylate-terminated PEG can be reacted with the vinyl group of the silane, resulting in a PEG that is covalently bonded to the surface of the medication device.
  • a hydrophilic surfactant is applied to the selected surface of the medical device to significantly reduce adso ⁇ tion of a protein-based medication such as insulin.
  • a protein-based medication such as insulin.
  • hydrophilic surfactants are available for this pu ⁇ ose, including but not limited to Genapol, a block ethylene/propylene copolymer having a molecular weight of about 1800 Daltons, available from Hoechst Celanese Co. of Somerville, New Jersey.
  • Other hydrophilic surfactants include Tween, a polyoxyethylene sorbitan available from Sigma Biochemicals of St. Louis, Missouri, and Brij, a polyoxyethylene ether also available from Sigma Biochemicals of St. Louis, Missouri.
  • These hydrophilic surfactants include a polyethylene glycol (PEG) moiety as their hydrophilic segment and are generally compatible with medications such as insulin.
  • a 1.0% solution of Genapol is prepared in isopropanol and then contacted with the selected surface, such as a metal or elastomeric surface of a medication device (or reservoir) by filling the medication device (or reservoir) with the Genapol solution.
  • the Genapol surfactant which is non-ionic in nature binds to the surface, and the isopropanol solvent can be readily removed under mild conditions of heat and vacuum.
  • the treated surface is placed in a radio frequency (RF) chamber in the presence of oxygen, argon, or both, and 100-200 watts of RF power are applied to result in covalent attachment of the polymer to the surface. If required, this process is repeated at least once.
  • RF radio frequency
  • An exemplary RF chamber is available from Technics, Inc. of Newark, New Jersey.
  • the oxygen and/or argon plasma generates significant ultraviolet light which creates reactive polymer sites which then covalently attach to the surface.
  • each RF step proceeded for about 10 minutes using an RF frequency of about 100 KHz.
  • the surface contact angle is less than 10 degrees as measured by direct contact angle measurement.
  • the contact angle of water is a measure of its hydrophilic characteristics.
  • a low contact angle means that the surface is wetted, whereas a high contact angle means that the surface is non- wetted or hydrophobic.
  • the contact angle of an untreated or uncoated polymeric surface ranges from about 88 to 125 degrees.
  • Protein adso ⁇ tion is significantly reduced as a result of the inventive surface treatment, typically to about 1.0 microgram or less per square centimeter of the treated surface, more specifically when measured with albumin or insulin.
  • insulin adso ⁇ tion after the foregoing Genapol surface treatment is less than 0.1 microgram per square cm of the surface, as compared to an adso ⁇ tion of about 1.5 microgram per square cm for the uncoated surface.
  • Similar surface treatments using other hydrophilic surfactants such as those identified above yield results of similar magnitude, although Genapol is believed to provide the best reduction in insulin adso ⁇ tion.
  • a further alternative coating method in accordance with the invention utilizes a hydrophilic polyurethane, such as that marketed by Thermedics, Inc. of Woburn, Massachusetts, under the name Biomer.
  • Biomer is prepared in an approximate 7.0% solution with tetrahydrofuran (THF) and the surface to be coated is dipped therein. The dip coated surface is subsequently dried for about six hours at about 45 degrees Celsius. Subsequent hydration as by exposure to water for about one hour results in a surface contact angle and insulin adso ⁇ tion profile that is too low to measure, i.e., less than about 0.04 micrograms per square centimeter.
  • a hydrophilic surface coating can also be prepared by the use of bovine serum albumin (BSA) dissolved in a phosphate buffered saline (PBS) solution with a concentration of about 5 milligrams per milliliter.
  • BSA bovine serum albumin
  • PBS phosphate buffered saline
  • the medication device surface to be coated is dipped into this solution and allowed to dry. After drying, the coated surface is dipped a second time into the BSA solution and then immediately dipped into a solution of glutaraldehyde in deionized water with a concentration of about 2.5% which functions to cross link the protein both to the surface and also to itself. After drying for about two hours, at about 37 degrees Celsius, the resultant surface contact angle is about 30 degrees, and it is believed that a comparable reduction in insulin adso ⁇ tion will result.
  • BSA bovine serum albumin
  • PBS phosphate buffered saline
  • a hydrophilic coating to the surface of the medication device.
  • these methods include radiation, electron beam and photo induced grafting, polymerization chemical grafting and plasma deposition of polymers.
  • these methods involve an energy source and a monomer of the desired hydrophilic polymer.
  • acrylonitrile can be grafted onto a surface by irradiation of acrylonitrile vapor in contact with the surface.
  • PAN polyacrylonitrile
  • a wide variety of polymers can be produced in this manner, the only requirement being that the monomer be available in reasonable purity with enough vapor pressure to be reactive in the deposition system.
  • the present invention provides a treated surface exhibiting significant hydrophilic properties, with a reduced surface contact angle, preferably of less than about 45 degrees, and more preferably less than about 35 degrees.
  • This treated surface has a low free energy and has provided demonstrated protein stability.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Vascular Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Materials Engineering (AREA)
  • Hematology (AREA)
  • Materials For Medical Uses (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne un dispositif médical comprenant une surface non métallique en contact avec une médication à base protéique choisie. Ladite surface présente un traitement superficiel fixé par covalence qui définit un angle de contact superficiel inférieur à environ 45 degrés et qui présente un profil d'adsorption de protéines inférieur à environ 1,0 microgramme par centimètre carré.
PCT/US2000/014642 1999-05-28 2000-05-26 Dispositif pour medication a revetement polymere superficiel de protection contre l'adhesion des proteines WO2000072896A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU51682/00A AU5168200A (en) 1999-05-28 2000-05-26 Medication device with polymeric surface coating protecting against protein adhesion

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US13670299P 1999-05-28 1999-05-28
US60/136,702 1999-05-28
US32478399A 1999-06-03 1999-06-03
US09/324,783 1999-06-03

Publications (2)

Publication Number Publication Date
WO2000072896A1 WO2000072896A1 (fr) 2000-12-07
WO2000072896A9 true WO2000072896A9 (fr) 2002-01-24

Family

ID=26834560

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/014642 WO2000072896A1 (fr) 1999-05-28 2000-05-26 Dispositif pour medication a revetement polymere superficiel de protection contre l'adhesion des proteines

Country Status (2)

Country Link
AU (1) AU5168200A (fr)
WO (1) WO2000072896A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020156434A1 (en) * 1998-03-13 2002-10-24 Minimed Inc. Stabilizing catheter for protein drug delivery
US6589591B1 (en) * 2001-07-10 2003-07-08 Baylor College Of Medicine Method for treating medical devices using glycerol and an antimicrobial agent
AU2005231417A1 (en) 2004-04-02 2005-10-20 Baylor College Of Medicine Novel modification of medical prostheses

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4626244A (en) * 1985-02-01 1986-12-02 Consolidated Controls Corporation Implantable medication infusion device
US4950256A (en) * 1988-04-07 1990-08-21 Luther Medical Products, Inc. Non-thrombogenic intravascular time release catheter
EP0433485B1 (fr) * 1989-12-21 1993-05-19 Siemens Aktiengesellschaft Dispositif pour remplir ou recharger de médicaments liquides un dispositif de dosage de médicaments implantable
US5328954A (en) * 1993-04-16 1994-07-12 Icet, Inc. Encrusting and bacterial resistant coatings for medical applications
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
DE69733307T2 (de) * 1996-11-01 2006-01-19 Medtronic MiniMed, Inc., Northridge Pumpe zur medikamentösen infusion mit einer durch ein protein stabilisierten beschichtung

Also Published As

Publication number Publication date
AU5168200A (en) 2000-12-18
WO2000072896A1 (fr) 2000-12-07

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