US20020133072A1 - Graft polymerization of substrate surfaces - Google Patents

Graft polymerization of substrate surfaces Download PDF

Info

Publication number
US20020133072A1
US20020133072A1 US10/035,561 US3556101A US2002133072A1 US 20020133072 A1 US20020133072 A1 US 20020133072A1 US 3556101 A US3556101 A US 3556101A US 2002133072 A1 US2002133072 A1 US 2002133072A1
Authority
US
United States
Prior art keywords
substrate
method
group consisting
selected
di
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.)
Abandoned
Application number
US10/035,561
Inventor
Guo-Bin Wang
Xianping Zhang
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.)
Angiotech BioCoatings Corp
Original Assignee
Angiotech BioCoatings Corp
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
Priority to US09/394,577 priority Critical patent/US6358557B1/en
Application filed by Angiotech BioCoatings Corp filed Critical Angiotech BioCoatings Corp
Priority to US10/035,561 priority patent/US20020133072A1/en
Assigned to STS BIOPOLYMERS, INC. reassignment STS BIOPOLYMERS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ZHANG, XIANPING, WANG, GUO-BIN
Publication of US20020133072A1 publication Critical patent/US20020133072A1/en
Assigned to CREDIT SUISSE, AS COLLATERAL AGENT reassignment CREDIT SUISSE, AS COLLATERAL AGENT SECURITY AGREEMENT Assignors: ANGIOTECH BIOCOATINGS CORP.
Assigned to ANGIOTECH BIOCOATINGS CORP. reassignment ANGIOTECH BIOCOATINGS CORP. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: STS BIOPOLYMERS, INC.
Assigned to ANGIOTECH BIOCOATINGS, INC. reassignment ANGIOTECH BIOCOATINGS, INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: CREDIT SUISSE
Assigned to ANGIOTECH BIOCOATINGS CORP. reassignment ANGIOTECH BIOCOATINGS CORP. CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED ON REEL 018606 FRAME 0632. ASSIGNOR(S) HEREBY CONFIRMS THE RELEASE OF SECURITY INTEREST. Assignors: CREDIT SUISSE
Application status is Abandoned legal-status Critical

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING LIQUIDS OR OTHER FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING LIQUIDS OR OTHER FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00Processes for applying liquids or other fluent materials
    • B05D1/18Processes for applying liquids or other fluent materials performed by dipping
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08Materials for coatings
    • A61L29/085Macromolecular materials

Abstract

The invention includes a method of coating a substrate, comprising exposing a substrate to an initiator capable of initiating a graft polymerization reaction on the substrate, to generate reactive radical sites on the surface of the substrate; contacting the substrate with a composition comprising one or more monomers in a medium which has different hydrophilicity compared to the substrate, and grafting monomer molecules onto the substrate by forming covalent bonds between monomer molecules and the substrate at reactive radical sites on the substrate surface. With the invention, novel coated articles can be obtained which are particularly useful as medical products such as catheters.

Description

    FIELD OF THE INVENTION
  • The present invention relates to methods for grafting polymers and copolymers onto polymer substrates. [0001]
  • BACKGROUND OF THE INVENTION
  • It is desirable for substrates such as those used in certain medical devices, including but not limited to catheters and tubes which are inserted into blood vessels, body cavities or tissues, or into the respiratory tract including the trachea, or inserted through other catheters or tubes, to have smoothness to ensure that such devices may be introduced without causing trauma to tissue encountered during their placement. The surfaces may be further enhanced by having lubricity for preventing injury or inflammation of mucous membranes or other surrounding tissues that may be caused when the devices remain in place. [0002]
  • In some instances, it is advantageous for medical device surfaces to have the capability to serve as a depot for various physiologically or pharmacologically active agents. Antithrombogenic materials, such as complexes of heparin with quaternary ammonium compounds, have been used on medical device surfaces to prevent thrombus formation on the surface of a medical device, as described in U.S. Pat. No. 5,069,899. In order to control nosocomial infections, anti-microbial agents including penicillins, cephalosporins, fluoroquinolones, aminoglycosides, silver compounds, phenols, biguanides, and others, have been proposed for use in surface coatings on the surfaces of implanted prostheses, as described in U.S. Pat. Nos. 5,069,899 and 4,442,133. [0003]
  • Many of the plastic materials of which such devices are ordinarily constructed are not easily treated with conventional surface enhancing methods. Materials used to make catheters are mostly hydrophobic and resist to one degree or another treatments designed to make them more biocompatible. Polymers such as silicones, latex rubbers, polyolefins, and many polyesters and polyamides have very low surface energies, often less than 40 dynes/cm[0004] 2. Furthermore, these surfaces are often very resistant to dissolution in or swelling by solvents that ordinarily are used in the coating industry. Also, these surfaces often lack functional groups susceptible to interactions such as hydrogen bonding or Van der Waals forces, which are commonly utilized to promote improved adhesion of surface layers. Technologies that have been proposed to overcome these shortcomings fail to address a number of the difficulties associated with the surface treatment of such medical devices.
  • Flame treatments are widely applied in surface modification to introduce oxygen-containing functions at polyolefin surfaces, mainly to improve printability or paintability. (F. Garbassi, M. Morra, E. Occhiello, [0005] Polymer Surfaces, From Physics to Technology, John Wiley & Sons, Chichester, (1994)). Active species formed by the high temperatures include radicals, ions, and molecules in excited states. Such treatments have not been used widely in the medical device industry. The harsh conditions of flame treatments generally could be harmful to the relatively fragile devices, and they have not been useful in treating device lumens.
  • Corona treatments exploit the corona affect, i.e. the formation of high energy electromagnetic fields close to thin wires or points, with consequent ionization in their proximity, even at atmospheric pressure and relatively low temperatures. Excited species (ions, radicals, electrons, molecules in excited states, etc.) are present in the ionized region, and are active in surface modification, typically the introduction of oxygen-containing functions. (F. Garbassi, M. Morra, E. Occhiello, [0006] Polymer Surfaces, From Physics to Technology, John Wiley & Sons, Chichester, (1994)). Although this process may be suitable for treating film webs, it is not suitable for treating device lumens and has not found wide application in the medical device industry.
  • “Cold Plasma” treatments require low pressure to be sustained at low temperatures. An ionized region is formed, including high energy photons, electron, ions, radicals, and excited species, with its composition depending on a gas feed. Low pressure plasmas can be employed for surface activation by the introduction of oxygen-containing functional groups, etching by formation of gaseous species (e.g., carbon oxides or fluorides in CF[0007] 3/O2 plasmas), or coating deposition by plasma polymerization (e.g., of fluorine or silicon-containing monomers). (F. Garbassi, M. Morra, E. Occhiello, Polymer Surfaces, From Physics to Technology, John Wiley & Sons, Chichester, (1994)). Cold plasma treatments have been used in the medical device industry but generally have not been effective at treating device lumens that are long or of small diameter.
  • “Hot Plasma” treatments are performed at atmospheric pressure at very high temperatures (5,000 to 10,000° K.). While these treatments have gained widespread use in the metallurgy industry, they generally are not useful with polymeric medical devices because of the extremely high temperatures that are required. [0008]
  • Ultraviolet (UV) treatments employ photons, usually having low wavelength and high energy, which are used to activate a variety of chemical reactions. A typical example of UV action on polymer surfaces is surface degradation by sun exposure. UV lamps have been used for the treatment of polymer surfaces, with the apparatus involving a lamp and sample illumination devices. A review of literature on UV-cured coatings can be found in C. -M. Chan, T. -M. Ko, and H. Hiraoka, [0009] Surf. Sci. Rep., 24,1 (1996), and R. R. Rye, J. Polym. Sci. Phys. Ed. 26, 2133 (1988). UV-induced graft polymerization is used to treat and modify medical devices. However such treatment has limited application. Many medical devices are deliberately treated to make them opaque to such radiation, and it is difficult to treat device lumens, especially smaller, longer lumens, unless the device is transparent to the UV radiation.
  • Free radical graft copolymerization has been used to modify material surfaces. Highly reactive free radical transferring creates reactive radical sites on the substrate surface, which are able to initiate copolymerization with available monomers, or reactive oligomers, thereby generating a graft polymer layer. Two major difficulties with such an approach are the ability to create a substantial number of substrate radicals, and to significantly reduce the amount of homopolymerization initiated by initiator radicals along with the graft copolymerization. (M. P. Stevens, Polymer chemistry: an introduction, Addison-Wesley, London (1975)). [0010]
  • Graft polymerization of medical catheters and other medical devices has been utilized to provide surfaces having different properties from the bulk polymers forming the body of the device. Such treatments typically use plasma or UV as a source of energy to promote the graft polymer formation and attendant covalent bonding to the surface. [0011]
  • In U.S. Pat. No. 5,447,799, Loh, et al. describe a process for depositing polymeric materials on surfaces, first by providing a layer of polymeric material on the surface by glow discharge polymerization of a mixture of silane and a vaporizable hydrocarbon monomer or a vaporizable organosilane monomer, and then providing a second layer of another polymeric material, on the first polymeric material, by vapor deposition polymerization of aromatic hydrocarbons or unsaturated hydrocarbons. [0012]
  • Kolesinski et al. U.S. Pat. No. 5,211,993 describes a method of preparing chromatographically active support material by coating surfaces of a comminuted inorganic substrate material with a monomer which, when polymerized, has chromatographic properties. Such monomers are said to include vinyl stearate, polyethylene glycol 1000 monomethacrylate, and stearyl methacrylate. Such treatments have the shortcoming of requiring expensive plasma generating apparatus to modify the device surface. [0013]
  • U.S. Pat. No. 5,741,551 describes methods for providing a polymer coating on a solid substrate by applying a coating of reactive chemicals having photo-activatable ketones covalently bonded to them, and irradiating with UV light to induce covalent bonding of the reactive chemicals to the substrate, followed by reacting a layer of monomer, oligomer, or polymer with the covalently bound reactive chemicals to produce a polymeric layer which is covalently bound to the substrate. U.S. Pat. No. 5,002,582 describes a method of applying a polymer coating onto a substrate that involves coating a surface with a mixture of polymer and polymer having covalently bound photo-activatable groups, and irradiating the material with UV light to induce covalent bonding of the coating to the substrate. These methods require radiation sources and are not suitable for the effective application of lumen coatings. [0014]
  • Lee, et al. U.S. Pat. No. 5,663,237 describes that graft polymer layers can be created on plastic surfaces by heating a mixture of monomer(s), polymerization initiator, and a supercritical solvent which is capable of at least superficial penetration into the device plastic surface in a pressure reactor. Disadvantages of the method include the need for high pressure and temperature, the presence of harmful reactive polymerization initiator in the graft polymer layer, the need for “supercritical” solvents to penetrate the device surface, and the inability to use the technique on surfaces for which supercritical solvents are unavailable. [0015]
  • A need exists for a means of providing polymer coatings on surfaces, particularly on surfaces such as polyolefins (such as polyethylene), silicones, polyamides, latex rubber, etc., onto which it is difficult for conventionally applied coatings to adhere. There is a particular need for providing polymer coatings in a convenient, inexpensive manner, and to apply coatings to the exterior and interior surfaces of devices. [0016]
  • SUMMARY OF THE INVENTION
  • The present invention relates to polymeric substrates and treatments which form polymers and modify the surface properties of the substrate. The invention includes a method of coating a substrate, comprising exposing a substrate with an initiator capable of initiating a graft polymerization reaction on the substrate; generating reactive radical sites on the surface of the substrate; contacting the substrate with a composition comprising a monomer in a medium which optionally has reversed phase properties compared to the substrate, in terms of hydrophilicity; and grafting the monomers onto the substrate by forming covalent bonding at reactive radical sites on the substrate surface, and accomplishing graft polymerization. [0017]
  • Preferably, the invention employs a salting out effect to favor graft polymerization instead of homopolymerization of the monomers. The invention permits graft polymerization of substrates at relatively low operating and capital costs, can accommodate polymerization of substrates of varied shapes, and can be utilized in relatively large batch operations. The invention is particularly useful in coating the lumen of polymeric substrates of varying dimensions, which are useful as medical devices. [0018]
  • The invention comprises a method of providing a solid surface with desired characteristics comprising contacting a substrate with an initiator of similar hydrophilicity as the substrate, and contacting the substrate with a medium having a surface tension that differs from the surface energy of the substrate, and in which the initiator is poorly soluble. Optionally the medium has reversed phase properties in terms of hydrophilicity, compared to the substrate. The medium preferably contains monomers having desired surface characteristics for the polymer substrate. The medium preferably is subject to mixing during contact with the substrate, to promote uniform dispersion of the monomer. The reaction preferably is performed at temperatures from about 20° C. to about 100° C. and at pressures from about 0.5 atmosphere to about 50 atmospheres. Optionally, the medium can contain salts or other materials having a relatively high solubility in the medium. [0019]
  • Suitable media include, but are not limited to, organic solvents and aqueous solutions, optionally containing dissolved ions or other substances which are very soluble in the medium and which will encourage graft polymerization. Suitable initiators include but are not limited to peroxide initiators, azo initiators, redox initiators, and photo-initiators/photosensitizers/thermal initiators. Hydrophilic or hydrophobic monomers can be used. Optionally, one or more cross-linking agents can be employed, such as cross-linking agents containing di- or multi-unsaturated functional groups. One embodiment of the present invention comprises a method of coating a lumen of a device by a reverse phase graft polymerization method described herein. [0020]
  • The present invention is applicable to a variety of substrates, including medical devices comprising silicone, polyethylene, polyamide and latex. With the invention, such devices can undergo surface modification by reversed phase graft polymerization, providing the device with altered surface characteristics, such as improved lubriciousness, and/or the ability to serve as a drug reservoir. [0021]
  • Thus, according to the invention, polymers and copolymers can be grafted onto polymer substrates to provide a surface with various functions, including but not limited to hydrophilicity, lubricity, ability to serve as a primer or tie coat, and ability to serve as a reservoir for physiologically or pharmacologically active agents. The reversed-phase graft polymerization of the instant invention permits hydrophilic polymer coatings on difficult-to-adhere-to surfaces, is capable of being applied to both interior an exterior surfaces of devices, and is relatively convenient and inexpensive. [0022]
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • The invention provides methods for graft polymerization, preferably reversed-phase graft polymerization, enabling the grafting of polymers and copolymers onto polymer substrates in order to serve a variety of functions. Examples include, but are not limited to, the use of a graft polymer capable of absorbing large quantities of water in order to provide moisture absorption or lubricity; the use of the graft polymer as a tie coat in order to allow succeeding layers to adhere; the use of the graft polymer to provide functional groups to attach physiologically or pharmacologically active agents; and the use of the graft polymer as a drug depot permitting the delivery of various drugs from the graft polymer. Optionally drugs can be mixed in with the polymer or bound to the functional groups with ionic forces. [0023]
  • Devices that could be provided with different surface characteristics by this method include but are not limited to medical devices, including but not limited to catheters, guide wires and medical instruments. Examples include, but are not limited to, PTCA catheters, cardiology catheters, central venous catheters, urinary catheters, drain catheters, and dialysis catheters. [0024]
  • Properties which can be provided to devices of the invention include, but are not limited to, hydrophobic coatings on hydrophilic substrates, hydrophilic coatings on hydrophobic substrates, non-conductive coatings on conductive surfaces, conductive coatings on non-conductive surfaces., acidic or basic coatings on pH-neutral substrates, non-thrombogenic coatings on thrombogenic substrates, thrombogenic coatings on non-thrombogenic substrates, and coatings with radio-isotopic magnetic, antibiotic and anticancer properties. According to the invention, a graft polymerization is performed by selecting an appropriate initiator and a polymerization medium, based on the nature of the substrate and the required surface properties. Appropriate initiators preferably will orient free radicals to attack the substrate surface and create the reactive radical sites on the substrate necessary to initiate graft polymerization. The graft polymerization generates a surface polymer layer as a surface coating which adheres well to various substrates, including polymer substrate surfaces which are difficult to adhere to. [0025]
  • Many inert surface materials have low surface energy. In the present invention, media with surface tensions of a magnitude differing from the surface energy of the substrate are selected in order to perform the process of modifying this group of materials. Optionally, for hydrophobic substrates, hydrophobic initiators and hydrophilic media are selected. Most preferably, the medium, on the one hand, and the substrate and the initiator, on the other hand, have a sufficiently different hydrophilicity so that the reaction will favor graft polymerization on the substrate instead of homopolymerization in the medium. The properties of the modified surface reflect the properties of the graft copolymer which in turn depend on the monomers chosen. The monomers preferably are sufficiently dissolved in the medium to permit the graft polymerization reaction to occur. Alternatively, monomers can be dispersed in the medium by suspension. Preferably, if the substrate is hydrophilic, hydrophilic initiators are used, if hydrophobic, preferably hydrophobic initiators are used. [0026]
  • The substrate can be of any suitable form or shape, including but not limited to tubing, sheets, fibers, strips, films, plates, filaments, pellet resins, powders, and extruded, molded or cast articles. Optionally, the substrate can comprise a medical device, including but not limited to catheters and drains. The substrate can be hydrophobic or hydrophilic. [0027]
  • The method of the present invention preferably comprises dissolving or dispersing one or more monomers in a medium containing an appropriate solvent or solvent mixture. The substrate or substrates are coated or otherwise contacted with the initiator, such as a solution containing the initiator, and optionally then dried. Optionally, the solution containing the initiator can contain a small amount of polymer which is soluble in the medium to adhere the initiator on the substrate temporarily. Preferably, the initiator is coated or otherwise placed onto the substrate surface prior to contacting the substrate with the medium. However, the initiator optionally can be placed in the medium, either alone or in conjunction with coating or otherwise placing it on the substrate. [0028]
  • The monomer solution comprises suitable concentrations of appropriate monomers, preferably at a concentration from about 2 to about 6 w/w %, in a medium selected based on the properties of the substrate and monomer. Preferably, an initiator-coated substrate is placed in a reaction vessel which contains the monomer solution. Optionally, the substrate, uncoated with initiator, can be placed into a reaction vessel which contains the initiator in the medium. Preferred reaction vessels include those having glass or stainless steel surfaces. [0029]
  • Preferably, the system is degassed by vacuum to prevent air bubbles forming between the reversed-phase substrate-solution interface, and then the graft polymerization reaction is allowed to proceed. However, degassing is not required. The presence of oxygen is not believed to significantly affect the graft polymerization reaction. Preferably, the reaction is conducted under an ambient atmospheric gas mixture. However, the reaction can be conducted under any suitable gas mixture, including nitrogen, argon, helium and neon. [0030]
  • The graft polymerization reaction pressure preferably is less than about 50 atmospheres, preferably from about 0.5 to about 50 atmospheres, more preferably from about 0.5 to about 10 atmospheres;, and even more preferably from about 0.75 to about 3 atmospheres. A reaction pressure of about 1 atmosphere is most preferred. [0031]
  • The graft polymerization reaction preferably is conducted at a temperature in the range from about from about 10° C. to about the boiling point of the medium solvent at the employed pressure. At atmospheric pressure, using an aqueous solvent, the reaction temperature preferably is less than about 100° C. More preferably, the reaction temperature is from about 40° C. to about 90° C., and most preferably from about 80° C. to about 90° C., at atmospheric pressure. At pressures higher than atmospheric, the reaction can take place at higher temperatures. Suitable reaction times can range from about ten minutes up to several hours, or longer. Monomer reactivity and initiator decomposition are related to temperature. Generally, the reaction rate is increased with increased temperature, allowing a shorter reaction time. The upper limit of the reaction temperature is governed by the boiling point of the medium, and the thermal tolerance of the substrate, at the reaction pressure. [0032]
  • The process can be accelerated by removing any inhibitor which was included with the monomer source to prolong monomer shelf life, especially when high levels of inhibitors or low reactivity monomers are used. However, generally it is unnecessary to remove the inhibitor contained in the monomer. [0033]
  • Preferably, the medium is stirred during the time it is in contact with the substrate to promote graft polymerization. If the substrate is in the form of a hollow tube, or contains a lumen, preferably the medium is pumped through the lumen in order to promote graft polymerization of the interior surface or lumen of the substrate. The reaction system often contains solid substrate and liquid medium and in that sense is heterogeneous. Also, differences in hydrophilicity between the medium and the substrate can cause the heterogeneous nature of the system. Promoting homogeneity of the medium and availability of monomers in the region surrounding the substrate, e.g., by maintaining a relatively uniform temperature, can contribute to the uniformity of the graft coating. Therefore, moderate, continued stirring of the medium preferably is maintained during the reaction. However, overly vigorous stirring can slow graft polymerization, and is disfavored. [0034]
  • After the reaction has been completed to a sufficient degree, the substrate can be removed from reaction with the medium, either by removing the substrate from the vessel, or by removing the medium from the vessel. Any undesired monomers or polymers remaining in the graft layer may be removed by washing. Although initiators tend to remain attached to the substrate surface, they can decompose at elevated temperatures and become smaller fragments which can be removed easily. Any residual monomer, homopolymer, initiator, and decomposed fragments of initiator which are present on the substrate can be removed by washing in appropriate solvents at elevated temperature, and discarded. Suitable washing solvents include those which can dissolve monomers, homopolymers, initiator or initiator fragments but do not deform the substrate. [0035]
  • Hydrophobic substrates useful in this invention include but are not limited to solid synthetic or natural polymer materials. The substrate preferably is a solid, but the invention can include other suitable substrates, for example, cross-linked hydrogels. The preferred solid substrate materials include, but are not limited to: polyolefins, including but not limited to polyolefins such as polyethylene and polypropylene, polyisobutylene and ethylene-alphaolefin copolymers; silicone polymers; acrylic polymers and copolymers, including but not limited to polyacrylonitrile, polymethylmethacrylate, polyethylmethacrylate, polyethylacrylate, and other polyesteracrylates and polyestermethacrylates; fluoropolymers, including but not limited to polytetrafluoroethylene, chlorotrifluoroethylene, fluorinated ethylene-propylene, and polyvinyl fluoride; vinyl polymers, including but not limited to polyvinyl chloride, polyvinyl methyl ether, polystyrene, polyvinyl acetate, and polyvinyl ketones; vinyl monomer-containing copolymers, including but not limited to ABS; natural and synthetic rubbers, including but not limited to latex rubber, butadiene-styrene copolymer, polyisoprene, polybutadiene, butadiene-acrylonitrile copolymers, polychloroprene polymers, polyisobutylene rubber, ethylene-propylenediene copolymers, and polyisobutylene-isoprene; polyurethanes, including but not limited to polyetherurethanes, polyesterurethanes, polycarbonateurethanes and polysiloxaneurethanes; and polyamides, including but not limited to Nylon 6, Nylon 66, Nylon 10, and Nylon 11; polyesters; epoxy polymers; wool; cotton; silk; rayon; cellulose; and modified celluloses. [0036]
  • Hydrophilic substrates preferably are solids and include, but are not limited to: hydrophilic acrylic polymers, including but not limited to polyacrylamide, poly-2-hydroxyethylacrylate, poly-N,N′-dimethylacrylamide, polyacrylic acid, and polymethacrylic acid; vinyl polymers, including but not limited to poly-N-vinylpyrrolidone, and polyvinylpyridine; polymaleic acid; poly-2-hydroxyethyl fumarate; maleic anhydride; starch and polyvinyl alcohol. [0037]
  • The medium is selected according to the nature of the substrate and the particular substrate surface modification desired. The medium preferably does not appreciably dissolve the substrate, and most preferably does not result in any dissolution or swelling of the substrate. It is particularly preferred that the medium and substrate have significant differences in their relative hydrophilicity. For example, if a hydrophilic substrate is used, a hydrophobic medium preferably is chosen and if a hydrophobic substrate is used, a hydrophilic medium preferably is chosen. One benefit of employing substrate and medium materials with different relative hydrophilicity, such as materials with reversed phase properties in terms of hydrophilicity, is that this can increase the efficiency of generating substrate radicals. Also, homopolymerization of the monomer can be limited by the lack of the radicals in the medium. Although not wishing to be bound by theory, it is believed that, as a result of differences in hydrophilicity in the system, initiator radicals or organic propagating radicals are directed to and attack the substrate, rather than the monomers in the medium. [0038]
  • In a preferred embodiment, the invention includes a salting out effect to favor graft polymerization. To employ a salting out effect, materials, such as salts, that are characterized by relatively high solubility in the medium are included in, or added to, the medium to force the monomer(s) toward the substrate phase. Preferred salting agents include, but are not limited to, sodium, ammonium, and potassium salts. [0039]
  • In processes for modification of the surface of a hydrophobic substrate, a hydrophilic media preferably is employed. Aqueous solutions preferably are used as the media, more preferably containing ion strength reinforcing agents. Preferably, ions or buffers, including sodium, ammonium, potassium, chloride, phosphate, and acetate are used. In processes for modifying hydrophilic substrates, a hydrophobic medium preferably is used. In such processes, the preferred media is an organic solvent, preferably containing one or more of toluene, hexane, cyclohexane, benzene, xylene, tetrahydrofuran, and aliphatic alcohols. Although preferred, it is not necessary that the solvent be non-toxic. [0040]
  • The initiator should have an affinity for, and preferably similar hydrophilicity to, the selected substrate, and should be relatively insoluble or poorly soluble in the medium in order to reduce homopolymerization in the medium. The initiator should be capable of generating at least one, and preferably two or more, free-radicals with an affinity for the substrate, permitting the free radicals to attack the substrate surface to create functional groups capable of reacting with the monomer. [0041]
  • If highly hydrophobic organic initiators with symmetrical structures can generate two hydrophobic initiator free-radicals, this class of initiators can have a higher efficiency of initiator free-radical transference to the hydrophobic substrate than initiators that generate only one hydrophobic initiator radical. The insolubility or poor solubility of the initiator in the medium can limit initiator free-radical diffusion into the medium, and thereby inhibit initiation of homopolymerization of the monomers in the medium. Initiators that can be used in the practice of the present invention include, but are not limited to peroxides, azo initiators, redox initiators, photo initiators and photosensitizers which can be thermally initiated. Particularly preferred initiators include organic peroxides. [0042]
  • Optionally, thermal initiators (including but not limited to peroxide and azo initiators), and redox initiators can be used to perform graft polymerization on inner surfaces of the substrate, including but not limited to lumen surfaces if the devices comprising the substrate are hollow. Under appropriate initiation conditions, these initiators permit both the free radicals and monomers in the liquid medium to access the lumen and to perform graft polymerization. Thermal initiators can give relatively constant initiation rates during the process, while the initiation rate for redox initiators can decline quickly because of the rapid consumption of initiator components. Initiation by radiation, with and without proteolytic initiators, also can be useful in the invention, although such initiators can be somewhat limited in usefulness in lumens, since the penetration of the radiation through the wall of the lumen reduces the intensity of the radiation. [0043]
  • Preferred peroxide initiators include, but are not limited to, peroxyesters, including but not limited to 1,1-dimethyl-3-hydroxybutyl peroxyneodecanoate, α-cumyl peroxyneodecanoate, α-cumyl peroxyneoheptanoate, t-amyl peroxyneodecanoate, t-butyl peroxyneodecanoate, t-amyl peroxypivalate, t-butyl peroxypivalate, 2,5-dimethyl 2,5-di(2-ethylhexanoylperoxy)hexane, t-butylperoxy-2 ethylhexanoate, t-butylperoxyacetate, t-amylperoxyacetate, t-butylperbenzoate, t-amylperbenzoate, and t-butyl-1-(2-ethylhexyl)monoperoxycarbonate; peroxyketals, including but not limited to, 1,1-di(t-butylperoxy)-3,3,5-trimethyl-cyclohexane, 1,1-di(t-butylperoxy)-cyclohexane, 1,1-di(t-amylperoxy)-cyclohexane, ethyl-3,3-di(t-butylperoxy)-butyrate, and ethyl-3,3-di(t-amylperoxy)-butylperoxy)-butylrate; peroxydicarbonates, including but not limited to di(n-propyl)peroxydicarbonates, di(sec-butyl)peroxydicarbonates, and di(2-ethylhexyl)peroxydicarbonates; ketone peroxides, including but not limited to 2,4-pentanedione peroxide; hydroperoxides, including but not limited to cumene hydroperoxide, butyl hydroperoxide, and amyl hydroperoxide; dialkyl peroxides, including but not limited to dicumyl peroxide, dibutylperoxide, and diamylperoxide; diacyl peroxide, including but not limited to decanoyl peroxide, lauroyl peroxide, and benzoyl peroxide; and inorganic peroxides, including but not limited to hydrogen peroxide and potassium persulfate, and mixtures of the above. [0044]
  • Preferred azo initiators include but are not limited to azobisisobutyronitrile, azobiscumene, azo-bisiso-1,1,1-tricyclopropylmethane, 4-nitrophenyl-azo-triphenylmethane, and phenyl-azo-triphenylmethane. Preferred redox initiators include, but are not limited to, peroxide-amine systems, peroxide-metal ion systems, and boronalkyl-oxygen systems, such as are described in Hans-Georg Elias, [0045] Macromolecules, Plenum Press (New York, 1984). Photo initiators/photosensitizers which can be thermally initiated, include, but are not limited to, organic peroxide and azo initiators, benzophenone, benzophenone derivatives, and camphorquinone-N,N dimethyl-amino-ethyl-methacrylate.
  • The monomers in the present invention preferably should be selected so as to accomplish the desired graft polymerization reaction, and to provide compatibility with the substrate, and to impart the desired properties to the substrate. The term monomer is used to refer to both monomeric and oligomeric forms of molecules. Free radical polymerizable monomers or oligomers can be used in the invention. Preferably, vinyl monomers, and more preferably acrylic monomers, are used in the invention. To perform the graft coating if the monomers used are relatively, or even completely, insoluble in the medium, monomer suspensions could be made using dispersing agents, including but not limited to polyvinyl alcohol, and barium sulfate. Optionally, the addition of alcohol could increase the solubility of the monomers, to achieve the desired concentration in the medium. [0046]
  • Suitable hydrophilic monomers include, but are not limited to, hydroxyl substituted ester acrylate and ester methacrylate, including but not limited to 2-hydroxyethylacrylate, 2- and 3-hydroxypropylacrylate, 2,3-dihydroxypropylacrylate, polyethoxyethyl-, and polyethoxypropylacrylates; acrylamide, methacrylamide and its derivatives, including but not limited to N-methylacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N,N-dimethyl-aminoethyl, N,.N-diethyl-aminoethyl, 2-acrylamido-2-methyl-1-propanesulfonic acid, N-[3-dimethylamino)propyl]acrylamide, and 2-(N,N-diethylamino)ethyl methacrylamide; polyethylene glycol acrylates, polyethylene glycol methacrylates, polyethylene glycol diacrylates, polyethylene glycol dimethacrylates; polypropylene glycol acrylates, polypropylene glycol methacrylates, polypropylene glycol diacrylates, polypropylene glycol dimethacrylates; acrylic acid; methacrylic acid; 2- and 4-vinylpyridine; 4- and 2-methyl-5-vinylpyridine; N-methyl-4-vinylpiperidine; 2-methyl-1-vinylimidazole; dimethylaminoethyl vinyl ether; N-vinylpyrrolidone; itaconic, crotonic, fumaric and maleic acids, and mixtures thereof. [0047]
  • Hydrophobic monomers include, but are not limited to, ester acrylates and ester methacrylates including but not limited to methyl, ethyl, propyl, butyl, phenyl, benzyl, cyclohexyl, ethoxyethyl, methoxyethyl, ethoxypropyl, hexafluoroisopropyl and n-octyl-acrylates and -methacrylates; acrylamides and methacrylamides; dimethyl fumarate, dimethyl maleate, diethyl fumarate, methyl vinyl ether, ethoxyethyl vinyl ether, vinyl acetate, vinyl propionate, vinyl benzoate, acrylonitrile, styrene, alpha-methylstyrene, 1-hexene, vinyl chloride, vinyl methyl ketone, vinyl stearate, 2-hexene and 2-ethylhexyl methacrylate, and mixtures thereof. [0048]
  • Optionally, cross-linking agents can be used to provide a cross-linked polymer structure. Suitable agents include, but are not limited to, monomers having di- or multi-unsaturated functional groups, including but not limited to diacrylates and dimethylacrylates of -polyethylene glycol and -polypropylene glycol, trimethylolpropane triacrylate and trimethacrylate, di-trimethylolpropane, tetraacrylate, pentaerythritol tetraacrylate, and tetramethacrylate, divinylbenzene, divinyl sulfone silicone-containing diacrylates and dimethacrylates. [0049]
  • Many polymeric polymer devices are made of polymers, such as silicone rubber, polyethylene, and polypropylene, which have a hydrophobic surface. In many applications for these devices, it is desirable that the device have a hydrophilic, lubricious surface. For example, catheters used in angioplasty and angiographic procedures preferably are lubricious and hydrophilic, to promote ease of transport from the point of insertion to the desired position for imaging or treatment, such as a cardiac ventricle. With the invention, hydrophilic monomers, such as N-vinylpyrrolidone, acrylamide and derivatives, can form wet lubricious polymer coatings on the surface of a hydrophobic medical device, by reversed phase graft polymerization. Since the present invention allows the monomer solution to contact the inner lumen of hollow devices, lumen surface modification is readily performed. [0050]
  • With the invention, monomers substituted containing functional groups can be used, to provide functional groups on the polymer surface. Two significant applications for providing such functional groups on the polymer surface are to attach physiologically or pharmacologically active agents to the polymer and to employ the graft polymer as a tie coat for other coatings which otherwise might not adhere to the substrate. With the present invention, graft polymers can be created which contain functional groups to which biological agents such as penicillins, cephalosporins, fluoroquinolones, aminoglycosides, silver compounds, phenols, and biguanides can be attached. Monomers having functional groups including, but not limited to, carboxylic acid, amine, hydroxyl, and polyethylene glycol could be used in order to provide these functional groups on the surface after graft coating. [0051]
  • With the invention, monomers may also be used that may or may not contain functional groups and which can serve to provide the surface with properties such as wet lubricity, hardness, softness, or other physical properties. Such graft layers may also be used as a reservoir so that materials, such as drugs, can be entrapped in the graft layer and can be leached out when placed in moist environments, such as inside human patients. This can provide targeted drug delivery to various sites within the body. Typical drugs which can be entrapped within the graft layers include, but are not limited to, anti-infective agents, such as antibiotics (including aminoglycosides such as gentimicin and amikacin), antimicrobial agents, such as benzalkonium chloride, 2-bromo-2-nitropropane-1,3-diol (Cosmosil), and polyhexanide (Bronopol); antithrombogenic compounds, such as benzalkoniumheparinate, and trididecylmethylammonium heparinate; anticancer agents, such as paclitaxel, merbarone, and methotraxate; anti-inflammatories, such as dexamethasone; and other agents as may be desired. In this way, the agents may be entrapped with or without covalent interactions with functional groups that may or may not exist on the graft polymer(s), and one or both mechanisms (entrapment and covalent bonding) could be operating within a layer simultaneously. Also, the graft polymers can act as tie coats to other layers which can serve as drug reservoirs. [0052]
  • Since the coating is covalently bonded to the substrate, the surface coating in the present invention has strong adhesion to the substrate. The yield of graft polymer can be controlled, by changing the surface area and factors such as initiation rate, temperature, and monomer concentration, which influence molecular weight in traditional free radical polymerization. Accordingly, the amount and size of side chains can be controlled with the invention. [0053]
  • A preferred embodiment of the present invention comprises treating a silicone substrate by dip-coating the substrate with an initiator comprising an organic peroxide solution, preferably a 1 to 10% solution, in tetrahydrofuran (THF). Thereafter, the substrate is air-dried and placed in a medium comprising about 3.9 w/w % N,N-dimethylacrylamide and about 0.19 w/w % acrylamide, about 0.25 w/w % diacrylate crosslinker, about 15% w/w sodium chloride and about 0.02 w/w % polyvinylpyrrolidone. The system is optionally degassed and the reaction is performed at a temperature from about 20° C. to about 100° C., more preferably from about 80° C. to about 90° C., most preferably from about 85° C. to about 89° C., and at a pressure from about 0.5 atmospheres to about 50 atmospheres, more preferably from about 0.5 atmospheres to about 3 atmospheres. The reaction preferably is permitted to proceed for up to about 3 hours while there is gentle mixing of the medium by a magnetic stirrer. This system provides graft layers of reasonable smoothness on the substrate surface; a longer reaction could produce thicker, rougher coats. [0054]
  • Another preferred embodiment of the present invention comprises coating a silicone substrate with an initiator comprising organic peroxide solution, at a concentration of about 1 to 10 w/w %, preferably about 6 w/w %, in tetrahydrofuran (THF). The substrate can be air dried and then placed into a medium comprising 1.9 w/w % acrylamide, 4.3 w/w % polyethylene glycol acrylate, 14.5 w/w % sodium chloride, and 2.0 w/w % polyvinylpyrrolidone. The reaction is performed at a temperature from about 20° C. to about 100° C., more preferably from about 80° C. to about 90° C., most preferably from about 85° C. to about 89° C., and at a pressure from about 0.5 atmospheres to about 50 atmospheres, more preferably from about 0.5 atmospheres to about 3 atmospheres. At a temperature of about 85° C. to about 89° C., and a pressure of about 1 atmosphere, the reaction is permitted to proceed for up to about 50 minutes while there is gentle mixing of the medium. [0055]
  • In another preferred embodiment, reverse phase graft polymerization is used to produce a surface coating on a substrate for use as a primer, or tie coat. A preferred method includes coating a substrate, such as a silicone substrate with an initiator comprising organic peroxide solution, about 1 to 10 w/w %, preferably about 6 w/w %, in tetrahydrofuran (THF), followed by dip-coating in a solution comprising 1 w/w % polyurethane, 12% acrylic polymer, 1.2% epoxy polymer, 64.1% THF, 10.2% methyl ethyl ketone, 10% ethylene glycol monobutyl ether and 1.5% polyethylene glycol, and then drying, preferably at about 85° C. for up to about 4 hours. [0056]
  • In another preferred embodiment, non-reverse phase graft coating is used to produce a surface coating on a difficult to adhere to substrate for use as a primer, or tie coat. A preferred method could include coating a substrate, such as a silicone substrate with an initiator comprising organic peroxide such as benzoyl peroxide, 1 to 10 w/w % in tetrahydrofuran, allowing to air dry. The treated substrate could then be dipped in a solution comprising 10 to 15 w/w % acrylic monomer(s) in 64.1% THF, 10.2% methylethylketone, 1.5% polyethylene glycol, 5% hydroxyethylmethacrylate, and the balance ethylene glycol monobutyl ether at 60° C., for a period of four hours in a reflux condenser. This would produce a graft polymer layer on the silicone surface to which various polymer coatings would adhere well. Such polymer layers would include but not be limited to polyurethanes, acrylics, polyamides, cellulosics and others. [0057]
  • The following Examples are illustrative of the invention, and are not intended to limit the scope of the invention.[0058]
  • EXAMPLE 1
  • Medical-grade colorless silicone tubing (Helix Medical, 3.18 mm outer diameter×1.58 mm internal diameter×20 cm length), was first treated by standard dip-coating in an 8 w/w % benzoyl peroxide solution in tetrahydrofuran (THF) for 30 seconds. The tubing was air dried and then placed in a 6 cm×40 cm glass cylinder, open at one end, containing 800 gm of an aqueous monomer solution composed of 3.9 w/w % N,N-dimethylacrylamide and 0.19 w/w % acrylamide, 0.25 w/w % diacrylate crosslinker, 15 w/w % sodium chloride and 0.02 w/w % polyvinylpyrrolidone. The system was degassed at 1.0 mm Hg for 10 minutes. The reactor was placed in a water bath at 87° C. for 3 hours, and the reaction system was stirred gently on a magnetic stirrer. After 3 hours, the tubing was removed from the reactor and washed with water. [0059]
  • The treated tubing was tested for lubricity. This coating was strongly adherent to the substrate and decreased the coefficient of friction to 6.8% of the original coefficient, from 183 g for the uncoated substrate to 12.5 g after coating, when the samples were pulled with 70.8 g weight against polyvinyl chloride under deionized water. [0060]
    TABLE 1
    Contact angles (θ) of graft coated
    silicone rubber and silicone rubber control
    Samples Control Graft Coating
    Measurement Advancing θ Receding θ Advancing θ Receding θ
    Run 1 108.36 78.08 103.9  26.68
    Run 2 109.22 81.63 101.26 28.33
    Run 3 107.99 78.02 106.66 37.74
  • A sample of the graft-coated tubing also was dipped in 2.0 w/w % of solution of gentian violet in water and alcohol, then taken out immediately and rinsed under a running tap of deionized water for 5 minutes. Following the rinse, the coating had a blue staining indicating a hydrophilic surface. [0061]
  • EXAMPLE 2
  • Medical-grade colorless silicone tubing (Helix Medical, 3.18 mm outer diameter×1.58 mm internal diameter×20 cm length), was treated by standard dip-coating in 8 w/w % benzoyl peroxide in tetrahydrofuran (THF) for 30 seconds. The tubing was air dried and then placed in a 6 cm×40 cm glass cylinder, open at one end containing 800 gm of an aqueous monomer solution composed of 1.9 w/w % acrylamide, 4.3 w/w % polyethylene glycol acrylate, 14.5 w/w % sodium chloride and 2.0 w/w % polyvinylpyrrolidone. The system was degassed at 1.0 mm Hg for 10 minutes. The reactor was placed in a water bath at 87° C. for 50 minutes and the reaction system was stirred gently on a magnetic stirrer. After 50 minutes the tubing was removed from the reactor and washed with water. [0062]
  • A sample of the tubing was stained using the method described in Example 1, and showed a blue staining which indicated the presence of a hydrophilic surface on the substrate. After drying, the sample then was elongated up to 350%. After elongation, the sample returned to its original configuration with no evidence of cracking, crumbling, or delamination, and the visual appearance of the sample remained the same as prior to elongation. [0063]
  • The graft coated and stretched sample of the tubing was tested for graft adhesion. A strip of adhesive tape (Scotch tape (3M)) was pressed firmly over the sample and removed quickly. No blue coating spots adhered to the tape. [0064]
  • Unstretched coated samples were soaked for 5 minutes in aqueous solutions containing antimicrobial agents with w/w concentrations as shown in Table 2, and then rinsed with deionized water. They were air dried and then incubated for 24 hours at 37° C. on standard method agar against [0065] S. aureus, and evaluated by zone of inhibition. The inhibition zone diameter of the treated samples against S. aureus is given in Table 2.
    TABLE 2
    Inhibition zone diameter (four runs) against S. aureus
    Zone size (mm)
    Uncoated silicone tubing Graft coated silicone
    Antimicrobial (control) tubing
    4.8% rifamycin 17, 19, 20, 26 32, 33, 33, 35
    1.9% gentamicin lauryl Not tested 12, 12, 12, 13
    sulfate
    2% vantocil 0, 0, 0, small 9, 9, 10, 10
    4.8% benzalkonium 0, 0, small, small 16, 16, 16, 16
    chloride
    2% 2-bromo-2- Not tested 38, 38, 38, 38
    nitropropane-1,3-diol
    2% silver nitrate Not tested 11, 12, 12, 12
    2% Germall plus Not tested 8, 8, 8, 8
    1% methotraxate Not tested 10, 11, 11, 11
    1% paclitaxel Not tested 6, 6, 6, 7
  • EXAMPLE 3
  • Interior coated samples made according to Example 1 were placed in a monomer solution made according to Example 2, composed of 1.9 w/w % acrylamide, 4.3 w/w % polyethylene glycol acrylate, 14.5 w/w % sodium chloride, and 2.0 w/w % polyvinylpyrrolidone. A graft polymerization reaction was performed using the procedure set forth in Example 1, except that instead of stirring, the reaction solution was circulated vertically upwardly through the tubing by a roller pump. After 50 minutes the tubing was removed from the reactor, and washed with water. [0066]
  • A sample of the tubing was stained using the method described in Example 1, and a blue color on the interior surface of the tubing indicated the presence of the coating on the inner surface of the tubing. [0067]
  • EXAMPLE 4
  • Initiator-coated samples made according to Example 1 and silicone tubing samples without initiator coating were placed in a monomer solution made according to Example 2. Graft polymerization was performed according to the procedure used in Example 1. After graft polymerization, the samples that were not coated with initiator were rinsed and stained using the method of Example 1. The blue dyed surface indicated the presence of the graft coating on these samples. This demonstrates that initiator can diffuse through the medium and cause graft polymerization without inducing significant homopolymerization [0068]
  • EXAMPLE 5
  • Samples cut from a latex rubber glove (VWR Scientific Products, Inc.) were dip-coated with an initiator solution, in the same method set forth in Example 1. Then, graft polymerization was performed using an aqueous monomer solution composed of 1.9 w/w % acrylamide, 4.3 w/w % of polyethylene glycol acrylate, 14.5 w/w % sodium chloride, and 2.0 w/w % polyvinylpyrrolidone, using the procedures set forth in Example 1. After polymerization, the samples were stained as described in Example 1. The blue stain demonstrated that a graft coating was obtained. [0069]
  • EXAMPLE 6
  • Pieces of polyurethane tubing (Thermedics Inc.) were graft coated using the method described in Example 5. The coated samples were stained according to the method of Example 1. The significant blue staining demonstrated that graft coating on the surface. [0070]
  • EXAMPLE 7
  • Pieces of polyethylene tubing were dip-coated with an initiator solution comprising 8 w/w % benzoyl peroxide in tetrahydrofuran (THF) for 30 seconds. The tubing was air dried and then placed in a long reactor containing an aqueous medium comprising 30.0 w/w % acrylamide, 2.0 w/w % polyvinylpyrrolidone, 15.0 w/w % sodium chloride. The system was degassed at 1.0 mm Hg for 10 minutes. The reactor was placed in a water bath at 85° C. for 40 minutes and the reaction system was stirred gently on a magnetic stirrer. After 40 minutes the tubing was removed from the reactor and washed with water. The sample was stained according to the method described in Example 1, which indicated a hydrophilic coating on the surface. [0071]
  • EXAMPLE 8
  • Samples of medical-grade colorless silicone tubing (Helix Medical, 3.18 mm outer diameter×1.58 mm internal diameter×20 cm length) were treated according to the method described in Example 2. The dry tubing samples were dip-coated in a solution comprising 1 w/w % polyurethane, 12% acrylic polymer, 1.2% epoxy polymer, 64.1% THF, 10.2% methyl ethyl ketone, 10% ethylene glycol monobutyl ether and 1.5% polyethylene glycol, and then dried at 85° C. for 4 hours. An adhesion test was conducted according to the method of Example 1, and the samples passed the test. [0072]
  • EXAMPLE 9
  • A piece of medical grade Tygon tubing (polyvinylchloride) was graft-coated according to Example 1. The sample was then stain tested according to Example 1, and the staining demonstrated the presence of a hydrophilic graft-coating of the sample surface. [0073]

Claims (35)

What is claimed is:
1. A method of coating a substrate, comprising:
exposing a substrate to an initiator capable of initiating a graft polymerization reaction on the substrate, to generate reactive radical sites on the surface of the substrate;
contacting the substrate with a composition comprising one or more monomers in a medium which has reversed phase properties compared to the substrate, in terms of hydrophilicity; and
graft polymerizing onto the substrate by forming covalent bonds between monomer molecules and the substrate it reactive radical sites on the substrate surface.
2. The method of claim 1, further comprising mixing the composition so that a plurality of said molecules remain in proximity to said reactive radical site.
3. The method of claim 1, wherein the monomers are grafted onto the substrate at a pressure less than about 50 atmospheres.
4. The method of claim 1, wherein the monomers are grafted onto the substrate at a temperature from about 10° C. to about 100° C.
5. The method of claim 1, wherein the substrate is selected from the group consisting of solid synthetic polymers and solid natural polymers.
6. The method of claim 5, wherein the substrate is selected from the group consisting of polyolefin, silicone polymer, acrylic polymer, acrylic copolymer, polyesteracrylate, polyestermethacrylate, fluoropolymer, vinyl polymer, vinyl monomer-containing copolymer, natural rubber, synthetic rubber, polyurethane, polyamide, polyester, epoxy polymer, wool, cotton, silk, rayon, and cellulose.
7. The method of claim 6, wherein the substrate is selected from the group consisting of polyethylene, polypropylene, polyisobutylene, ethylene-alphaolefin copolymer, polyacrylonitrile, polymethylmethacrylate, polyethylmethacrylate, polyethylacrylate, polytetrafluoroethylene, chlorotrifluoroethylene, fluorinated ethylene-propylene, polyvinyl fluoride, polyvinyl chloride, polyvinyl methyl ether, polystyrene, polyvinyl acetate, polyvinyl ketone, ABS, latex rubber, butadiene-styrene copolymer, polyisoprene, polybutadiene, butadiene-acrylonitrile copolymer, polychloroprene polymer, polyisobutylene rubber, ethylene-propylenediene copolymer, polyisobutylene-isoprene, polyetherurethane, polyesterurethane, polycarbonateurethane and polysiloxaneurethane, Nylon 6, Nylon 66, Nylon 10, Nylon 11, modified cellulose, polyacrylamide, poly2-hydroxyethylacrylate, polyN,N′-dimethylacrylamide, polyacrylic acid, polymethacrylic acid, polyN-vinylpyrrolidone, polyvinylpyridine, polymaleic acid, poly2-hydroxyethyl fumarate, maleic anhydride, starch, and polyvinyl alcohol.
8. The method of claim 1, wherein the medium is a hydrophilic aqueous solution.
9. The method of claim 8, wherein the medium contains one or more ions selected from the group consisting of sodium, ammonium, potassium, chloride, phosphate, and acetate buffers.
10. The method of claim 1, wherein the medium is hydrophobic, and comprises an organic solvent.
11. The method of claim 10, wherein the medium comprises a solvent selected from the group consisting of toluene, hexane, cyclohexane, and mixtures thereof.
12. The method of claim 1, wherein the initiator is selected from the group consisting of peroxide initiators, azo initiators, redox initiators, and photo-initiators/photosensitizers which can be thermally initiated.
13. The method of claim 12, wherein the initiator is a peroxide initiator selected from the group consisting of peroxyester, peroxyketal, peroxydicarbonate, ketone peroxide, dialkyl peroxide, diacyl peroxide, an inorganic peroxide, and mixtures thereof.
14. The method of claim 13, wherein the initiator is selected from the group consisting of 1,1-dimethyl-3-hydroxybutyl peroxyneodecanoate, α-cumyl peroxyneodecanoate, α-cumyl peroxyneoheptanoate, t-amyl peroxyneodecanoate, t-butyl peroxyneodecanoate, t-amyl peroxypivalate, t-butyl peroxypivalate, 2,5-dimethyl 2,5-di(2-ethylhexanoylperoxy)hexane, t-butylperoxy-2-ethylhexanoate, t-butylperoxyacetate, t-amylperoxyacetate, t-butylperbenzoate, t-amylperbenzoate, t-butyl-1-(2-ethylhexyl)monoperoxycarbonate, 1,1-di(t-butylperoxy)-3,3,5-trimethyl-cyclohexane, 1,1-di(t-butylperoxy)-cyclohexane, 1,1-di(t-amylperoxy)-cyclohexane, ethyl-3,3-di(t-butylperoxy)-butyrate, ethyl-3,3-di(t-amylperoxy)-butylperoxy)-butylrate, di(n-propyl)peroxydicarbonate, di(sec-butyl)perosydicarbonate, di(2-ethylhexyl)peroxydicarbonate, 2,4-pentanedione peroxide, cumene hydroperoxide, butyl hydroperoxide, amyl hydroperoxide, dicumyl peroxide, dibutylperoxide, diamylperoxide, decanoyl peroxide, lauroyl peroxide, benzoyl peroxide, hydrogen peroxide, potassium persulfate, and mixtures thereof.
15. The method of claim 12, wherein the initiator is an azo initiator selected from the group consisting of azobisisobutyronitrile, azobiscumene, azo-bisiso-1,1,1-tricyclopropylmethane, 4-nitrophenyl-azo-triphenylmethane phenyl-azo-triphenylmethane, and mixtures thereof.
16. The method claim 12, wherein the initiator is a redox initiator selected from the group consisting of peroxide-amine systems, peroxide-metal ion systems, and boronalkyl-oxygen systems.
17. The method of claim 12, wherein the initiator is selected from the group consisting of 1,1-dimethyl-3-hydroxybutyl peroxyneodecanoate, α-cumyl peroxyneodecanoate, (α-cumyl peroxyneoheptanoate, t-amyl peroxyneodecanoate, t-butyl peroxyneodecanoate, t-amyl peroxypivalate, t-butyl peroxypivalate, 2,5-dimethyl 2,5-di(2-ethylhexanoylperoxy)hexane, t-butylperoxy-2ethylhexanoate, t-butylperoxyacetate, t-amylperoxyacetate, t-butylperbenzoate, t-amylperbenzoate, t-butyl-1-(2-ethylhexyl)monoperoxycarbonate, 1,1-di(t-butylperoxy)-3,3,5-trimethyl-cyclohexane, 1,1-di(t-butylperoxy)-cyclohexane, 1,1-di(t-amylperoxy)-cyclohexane, ethyl-3,3-di(t-butylperoxy)-butyrate, ethyl-3,3-di(t-amylperoxy)-butylperoxy)-butylrate, di(n-propyl)peroxydicarbonate, di(sec-butyl)peroxydicarbonate, di(2-ethylhexyl)perosydicarbonate, 2,4-pentanedione peroxide, cumene hydroperoxide, butyl hydroperoxide, amyl hydroperoxide, dicumyl peroxide, dibutylperoxide, diamylperoxide, decanoyl peroxide, lauroyl peroxide, benzoyl peroxide, azobisisobutyronitrile, azobiscumene, azo-bisiso-1,1,1-tricyclopropylmethane, 4-nitrophenyl-azo-triphenylmethane, phenyl-azo-triphenylmethane, benzophenone, benzophenone derivatives, camphorquinone-N,N dimethyl-amino-ethyl-methacrylate, and mixtures thereof.
18. The method of claim 1, wherein the monomer is selected from the group consisting of hydrophilic monomers and hydrophobic monomers.
19. The method of claim 18, wherein the monomer comprises a hydrophilic monomer selected from the group consisting of hydroxyl substituted ester acrylate, ester methacrylate, 2-hydroxyethylacrylate, 2-hydroxypropylacrylate, 3-hydroxypropylacrylate, 2,3-dihydroxypropylacrylate, polyethoxyethylacrylate, polyethoxypropylacrylate, acrylamide, methacrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N,N-dimethyl-aminoethyl, 2-acrylamido-2-methyl-1-propanesulfonic acid, N,N-diethyl-aminoethyl, 2-acrylamido-2-methyl-1-propanesulfonic acid, N-[3-dimethylamino)propyl]acrylamide, 2-(N,N-diethylamino)ethyl methacrylamide, polyethylene glycol acrylate, polyethylene glycol methacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate; poly propylene glycol acrylate, polypropylene glycol methacrylate, polypropylene glycol diacrylate, polypropylene glycol dimethacrylate; acrylic acid, methacrylic acid, 2- and 4-vinylpyridine; 4- and 2-methyl-5-vinylpyridine, N-methyl-4-vinylpiperidine, 2-methyl-1-vinylimidazole, dimethylaminoethyl vinyl ether, N-vinylpyrrolidone, itaconic acid, crotonic acid, fumaric acid, maleic acid, and mixtures thereof.
20. The method of claim 18, wherein the monomer comprises a hydrophobic monomer selected from the group consisting of ester acrylates selected from the group consisting of methyl, ethyl, propyl, butyl, phenyl, benzyl, cyclohexyl, ethoxyethyl, methoxyethyl, ethoxypropyl, hexafluoroisopropyl and n-octyl-acrylates; ester methacrylates selected from the group consisting of methyl, ethyl, propyl, butyl, phenyl, benzyl, cyclohexyl, ethoxyethyl, methoxyethyl, ethoxypropyl, hexafluoroisopropyl and n-octyl-methacrylates; acrylamides; methacrylamides; dimethyl fumarate; dimethyl maleate; diethyl fumarate; methyl vinyl ether; ethoxyethyl vinyl ether; vinyl acetate; vinyl propionate; vinyl benzoate; acrylonitrile; styrene; alpha-methylstyrene; 1-hexene; vinyl chloride; vinyl methyl ketone; vinyl stearate; 2-hexene; 2-ethylhexyl methacrylate, and mixtures thereof.
21. A method of coating a substrate, comprising:
exposing a substrate to an initiator capable of initiating a graft polymerization reaction on the substrate, to generate reactive radical sites on the surface of the substrate;
contacting the substrate with a composition comprising one or more monomers in a medium which has reversed phase properties compared to the substrate, in terms of hydrophilicity, while mixing the composition;
graft polymerizing onto the substrate by forming covalent bonds between monomer molecules and the substrate at reactive radical sites on the substrate surface; and
contacting the substrate with a cross-linking agent.
22. The method of claim 21, wherein the cross-linking agent is selected from the group consisting monomers having di- or multi-unsaturated functional groups.
23. The method of claim 22, wherein the cross-linking agent is selected from the group consisting of diacrylates of polyethylene glycol, diacrylates of polypropylene glycol, dimethylacrylates of polyethylene glycol, dimethylacrylates of polypropylene glycol, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, di-trimethylolpropane, tetraacrylate, pentaerythritol tetraacrylate, tetramethacrylate, divinylbenzene, divinyl sulfone, silicone-containing diacrylates and dimethacrylates, and mixtures thereof.
24. The method of claim 1, wherein the substrate is silicone;
the initiator is an organic peroxide solution in tetrahydrofuran (THF);
the medium comprises from about 3% w/w to about 6% w/w acrylamide derivatives, from about 0.1% w/w to about 0.4% w/w diacrylate crosslinker, from about 10% w/w to about 20% w/w sodium chloride and from about 0.01% w/w to about 0.03% w/w polyvinylpyrrolidone; and,
the reaction is allowed to proceed at a temperature from about 80° C. to about 95° C. at atmospheric pressure.
25. The method of claim 1, wherein the substrate is silicone;
the initiator is an organic peroxide solution in tetrahydrofuran (THF);
the medium comprises from about 1.0% w/w to about 3.0% w/w acrylamide derivatives, from about 3.0% w/w to about 5% w/w polyethylene glycol acrylate, from about 10% w/w to about 20% w/w sodium chloride and from about 1.0% w/w to about 3.0% w/w polyvinylpyrrolidone; and
the reaction is allowed to proceed at a temperature from about 80° C. to about 95° C. at atmospheric pressure.
26. The method of claim 1, wherein the substrate is polyethylene;
the medium comprises from about 20% w/w to about 40% w/w acrylamide, from about 1% w/w to about 3% w/w polyvinylpyrrolidone, and from about 10% w/w to about 20% w/w sodium chloride; and
the reaction is allowed to proceed at a temperature from about 80° C. to about 95° C. at atmospheric pressure.
27. The method of claim 1, wherein the substrate is selected from the group consisting of silicone, polyethylene, polyamide and latex, and wherein the grafting coats the substrate surface with a coating having characteristics selected from the group consisting of lubricious, hydrophilic and elastic properties.
28. The method of claim 1, further comprising attaching to the coated substrate a biological agent selected from the group consisting of penicillins, cephalosporins, fluoroquinolones, aminoglycosides, silver compounds, phenols, and biguanides.
29. A method of coating a substrate, comprising:
exposing a substrate to an initiator capable of initiating a graft polymerization reaction on the substrate, to generate reactive radical sites on the surface of the substrate;
contacting the substrate with a composition comprising one or more monomers in a medium; and
graft polymerizing onto the substrate at a pressure less than about 50 atmospheres by forming covalent bonds between monomer molecules and the substrate at reactive radical sites on the substrate surface.
30. The method of claim 29, wherein said graft polymerization is accomplished at a pressure less than about 10 atmospheres.
31. A medical device comprising:
a substrate constructed and arranged for insertion into a patient; and
a plurality of monomer molecules graft polymerized onto the surface of the substrate from a medium having reversed phase properties from the substrate, in terms of hydrophilicity.
32. A medical device according to claim 31, wherein the substrate is selected from the group consisting of guide wires, and catheters selected from the group consisting of PTCA catheters, cardiology catheters, central venous catheters, urinary catheters, drain catheters, and dialysis catheters.
33. A medical device according to claim 31, wherein the substrate defines at least one lumen, at least a portion of which is coated with monomer molecules graft polymerized to the lumen surface.
34. A medical device according to claim 33, wherein the substrate defines both interior and exterior surfaces of a lumen, and at least a portion of both the interior and exterior of the lumen is coated with monomer molecules graft polymerized to the lumen surface.
35. A system for forming a graft polymerized medical device comprising:
a substrate constructed and arranged for insertion into a patient;
an initiator capable of initiating a graft polymerization reaction on the substrate, to generate reactive radical sites on the surface of the substrate; and
a composition comprising one or more monomers in a medium which has reversed phase properties compared to the substrate, in terms of hydrophilicity.
US10/035,561 1999-09-10 2001-11-07 Graft polymerization of substrate surfaces Abandoned US20020133072A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US09/394,577 US6358557B1 (en) 1999-09-10 1999-09-10 Graft polymerization of substrate surfaces
US10/035,561 US20020133072A1 (en) 1999-09-10 2001-11-07 Graft polymerization of substrate surfaces

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US10/035,561 US20020133072A1 (en) 1999-09-10 2001-11-07 Graft polymerization of substrate surfaces

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/394,577 Division US6358557B1 (en) 1999-09-10 1999-09-10 Graft polymerization of substrate surfaces

Publications (1)

Publication Number Publication Date
US20020133072A1 true US20020133072A1 (en) 2002-09-19

Family

ID=23559541

Family Applications (2)

Application Number Title Priority Date Filing Date
US09/394,577 Active US6358557B1 (en) 1999-09-10 1999-09-10 Graft polymerization of substrate surfaces
US10/035,561 Abandoned US20020133072A1 (en) 1999-09-10 2001-11-07 Graft polymerization of substrate surfaces

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/394,577 Active US6358557B1 (en) 1999-09-10 1999-09-10 Graft polymerization of substrate surfaces

Country Status (5)

Country Link
US (2) US6358557B1 (en)
EP (1) EP1214107A1 (en)
JP (1) JP2003510378A (en)
AU (1) AU6520600A (en)
WO (1) WO2001017575A1 (en)

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040071912A1 (en) * 2002-09-25 2004-04-15 Berth Jorgen Mikael Method for improving fire resistance of polyethylene tubing and polyethylene tubing manufactured according to said method
US20040225053A1 (en) * 2003-05-06 2004-11-11 Atofina Chemicals, Inc. Polymerization of fluoromonomers using a 3-allyloxy-2-hydroxy-1-propanesulfonic acid salt as surfactant
US20040267359A1 (en) * 2003-06-27 2004-12-30 Harish Makker IOL insertion apparatus and methods for making and using same
US20050013836A1 (en) * 2003-06-06 2005-01-20 Board Of Regents, The University Of Texas System Antimicrobial flush solutions
US20050197634A1 (en) * 2004-01-20 2005-09-08 Board Of Regents, The University Of Texas System Methods for coating and impregnating medical devices with antiseptic compositions
US20060142339A1 (en) * 2003-06-19 2006-06-29 Bosmans Jean-Paul R M Aminosulfonyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht 4-antagonists
US20070106232A1 (en) * 2003-06-16 2007-05-10 Rider Ii Deal L Method and apparatus for extending feeding tube longevity
US20070270447A1 (en) * 2002-05-24 2007-11-22 Angiotech International Ag Compositions and methods for coating medical implants
WO2008060522A3 (en) * 2006-11-10 2008-07-10 Univ California Atmospheric pressure plasma-induced graft polymerization
US20080183152A1 (en) * 2001-01-12 2008-07-31 Issam Raad Medical devices with broad spectrum antimicrobial activity
US20090062909A1 (en) * 2005-07-15 2009-03-05 Micell Technologies, Inc. Stent with polymer coating containing amorphous rapamycin
US20090123515A1 (en) * 2005-07-15 2009-05-14 Doug Taylor Polymer coatings containing drug powder of controlled morphology
US20090326165A1 (en) * 2007-09-25 2009-12-31 Patil Damodar R Method of making graft copolymers from sodium poly(aspartate) and the resulting graft copolymer
US20100030261A1 (en) * 2006-10-02 2010-02-04 Micell Technologies, Inc. Surgical Sutures Having Increased Strength
US20100236684A1 (en) * 2009-03-18 2010-09-23 Greg Garlough Plasma deposition to increase adhesion
US20100237043A1 (en) * 2009-03-18 2010-09-23 Greg Garlough Plasma deposition to increase adhesion
US20100255239A1 (en) * 2009-04-03 2010-10-07 Hammond Terry E Ultraviolet radiation curable pressure sensitive acrylic adhesive
WO2010111232A3 (en) * 2009-03-23 2011-04-21 Micell Technologies, Inc. Drug delivery medical device
US20120228262A1 (en) * 2009-09-25 2012-09-13 Kabushiki Kaisha Toshiba Pattern forming method
US8313760B2 (en) 2002-05-24 2012-11-20 Angiotech International Ag Compositions and methods for coating medical implants
US8795762B2 (en) 2010-03-26 2014-08-05 Battelle Memorial Institute System and method for enhanced electrostatic deposition and surface coatings
US8834913B2 (en) 2008-12-26 2014-09-16 Battelle Memorial Institute Medical implants and methods of making medical implants
US8852625B2 (en) 2006-04-26 2014-10-07 Micell Technologies, Inc. Coatings containing multiple drugs
US8900651B2 (en) 2007-05-25 2014-12-02 Micell Technologies, Inc. Polymer films for medical device coating
US9433516B2 (en) 2007-04-17 2016-09-06 Micell Technologies, Inc. Stents having controlled elution
US9486431B2 (en) 2008-07-17 2016-11-08 Micell Technologies, Inc. Drug delivery medical device
US9510856B2 (en) 2008-07-17 2016-12-06 Micell Technologies, Inc. Drug delivery medical device
US9539593B2 (en) 2006-10-23 2017-01-10 Micell Technologies, Inc. Holder for electrically charging a substrate during coating
AU2016200311B2 (en) * 2011-12-14 2017-06-29 Arrow International, Inc. Luminal modifications for catheters
US9737642B2 (en) 2007-01-08 2017-08-22 Micell Technologies, Inc. Stents having biodegradable layers
US9789233B2 (en) 2008-04-17 2017-10-17 Micell Technologies, Inc. Stents having bioabsorbable layers
US9795762B2 (en) 2011-12-14 2017-10-24 Arrow International, Inc. Surface modification for dialysis catheters
US9902830B2 (en) 2015-02-04 2018-02-27 Alltech, Inc. Aflatoxin templates, molecularly imprinted polymers, and methods of making and using the same
US9981072B2 (en) 2009-04-01 2018-05-29 Micell Technologies, Inc. Coated stents
US10117972B2 (en) 2011-07-15 2018-11-06 Micell Technologies, Inc. Drug delivery medical device
US10188772B2 (en) 2011-10-18 2019-01-29 Micell Technologies, Inc. Drug delivery medical device
US10232092B2 (en) 2010-04-22 2019-03-19 Micell Technologies, Inc. Stents and other devices having extracellular matrix coating

Families Citing this family (112)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6001067A (en) 1997-03-04 1999-12-14 Shults; Mark C. Device and method for determining analyte levels
US8527026B2 (en) 1997-03-04 2013-09-03 Dexcom, Inc. Device and method for determining analyte levels
DE69918568T2 (en) * 1999-09-22 2005-08-25 SurModics, Inc., Eden Prairie Initiation group carrying a water-soluble coating agent and coating processes
WO2001027749A1 (en) * 1999-10-14 2001-04-19 Advanced Micro Devices, Inc. Apparatus and method for caching alignment information
AU6260001A (en) * 2000-05-12 2001-11-20 Logstar Ror A/S Coating composition for high density polyethylene tubing
DE60201889T2 (en) * 2001-02-28 2006-04-06 Covalon Technologies Inc., , Mississauga A process for preparing an antimicrobial polymer surfaces
US6858248B2 (en) * 2001-05-30 2005-02-22 Novartis Ag Method for applying a coating to a medical device
US8101196B2 (en) 2001-06-26 2012-01-24 Biointeractions, Ltd. Polysaccharide biomaterials and methods of use thereof
AT324187T (en) * 2002-06-27 2006-05-15 Fuji Photo Film Co Ltd Upper-surface functional element
US20030032874A1 (en) * 2001-07-27 2003-02-13 Dexcom, Inc. Sensor head for use with implantable devices
AU2002367825A1 (en) * 2001-07-30 2003-10-13 Sts Biopolymers, Inc. Graft polymer matrices
US7682669B1 (en) * 2001-07-30 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device
CA2460928A1 (en) * 2001-09-18 2003-03-27 Eidgenossische Technische Hochschule Zurich Methods and apparatus for coating surfaces
US7091127B2 (en) * 2001-09-18 2006-08-15 Ecole Polytechnique Federale De Lausanne Methods and apparatus for patterning a surface
US7348055B2 (en) 2001-12-21 2008-03-25 Surmodics, Inc. Reagent and method for providing coatings on surfaces
EP1506239B1 (en) * 2002-01-25 2006-03-22 Phenomenex, Inc. Surface graft modified resins and formation thereof
US20030195610A1 (en) 2002-04-04 2003-10-16 Herrmann Robert A. Processes for producing polymer coatings through surface polymerization
US20050237480A1 (en) * 2002-05-13 2005-10-27 The Regents Of The University Of California Chemical modifications to polymer surfaces and the application of polymer grafting to biomaterials
US7828728B2 (en) 2003-07-25 2010-11-09 Dexcom, Inc. Analyte sensor
US7431888B2 (en) * 2002-09-20 2008-10-07 The Regents Of The University Of California Photoinitiated grafting of porous polymer monoliths and thermoplastic polymers for microfluidic devices
CA2500067A1 (en) * 2002-09-26 2004-04-08 Endovascular Devices, Inc. Apparatus and method for delivery of mitomycin through an eluting biocompatible implantable medical device
US6884829B2 (en) * 2002-10-18 2005-04-26 Robert L. Albright Hemocompatible coated polymer and related one-step methods
ITTO20030039A1 (en) * 2003-01-24 2004-07-25 Fresenius Hemocare Italia Srl Filter for separating leukocytes from whole blood and / or blood-derived preparations, process for the manufacture of the filter, device and utilization.
US7026014B2 (en) * 2003-02-07 2006-04-11 Clemson University Surface modification of substrates
JP4903555B2 (en) * 2003-02-20 2012-03-28 ウィルソン−クック・メディカル・インコーポレーテッドWilson−Cook Medical Incorporated Medical devices and a manufacturing method thereof with a sticky coating
WO2004078811A1 (en) * 2003-02-25 2004-09-16 Nisshinbo Industries,Inc. Solvent for polymerization reaction and process for producing polymer
IES20030294A2 (en) 2003-04-17 2004-10-20 Medtronic Vascular Connaught Coating for biomedical devices
JP4718766B2 (en) * 2003-06-03 2011-07-06 テルモ株式会社 Blood filter
WO2005011520A2 (en) 2003-07-25 2005-02-10 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
AT356515T (en) * 2003-09-03 2007-03-15 Research In Motion Ltd Methods and apparatus for displaying a home network called
US7566502B1 (en) 2003-09-17 2009-07-28 Allegiance Corporation Surface modification of elastomeric articles
US20070087168A1 (en) * 2004-10-13 2007-04-19 Naoyuki Toriumi Liquid transport film
WO2005081655A2 (en) * 2004-02-17 2005-09-09 The Children's Hospital Of Philadelphia Gene and cell delivery self expanding polymer stents
US20050186258A1 (en) * 2004-02-20 2005-08-25 Shiping Wang Antimicrobial medical gloves
US7767220B2 (en) * 2004-04-23 2010-08-03 Boston Scientific Scimed, Inc. Implantable or insertable medical articles having covalently modified, biocompatible surfaces
KR100741565B1 (en) 2004-04-28 2007-07-23 강길선 A manufacturing method of composite for acrylic bone cement
US8277713B2 (en) * 2004-05-03 2012-10-02 Dexcom, Inc. Implantable analyte sensor
US7185753B2 (en) * 2004-09-28 2007-03-06 Hartness International, Inc. Shuttle conveyor
JP4739749B2 (en) * 2004-12-27 2011-08-03 三菱レイヨン株式会社 Composite material and manufacturing method thereof
US7767251B2 (en) * 2005-03-16 2010-08-03 Shiping Wang Repellent elastomeric article
US20060240312A1 (en) * 2005-04-25 2006-10-26 Tao Xie Diffusion media, fuel cells, and fuel cell powered systems
US8744546B2 (en) 2005-05-05 2014-06-03 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
US7772393B2 (en) 2005-06-13 2010-08-10 Innovative Surface Technologies, Inc. Photochemical crosslinkers for polymer coatings and substrate tie-layer
US20070048249A1 (en) * 2005-08-24 2007-03-01 Purdue Research Foundation Hydrophilized bactericidal polymers
US8343473B2 (en) 2005-08-24 2013-01-01 Purdue Research Foundation Hydrophilized antimicrobial polymers
US20070190333A1 (en) * 2006-02-13 2007-08-16 Mitsui Chemicals, Inc. Polyolefin-based molded product coated with polar polymer, method for producing the same, and uses of the same
JP5391520B2 (en) * 2006-02-21 2014-01-15 東レ株式会社 Method for producing a modified substrate
US7465777B2 (en) 2006-03-02 2008-12-16 Boston Scientific Scimed, Inc. Hybrid polymer materials from reactive extrusion for medical devices
US7872068B2 (en) * 2006-05-30 2011-01-18 Incept Llc Materials formable in situ within a medical device
US8124188B2 (en) * 2006-08-18 2012-02-28 Commonwealth Scientific And Industrial Research Organisation Polymeric coatings and methods for forming them
US8795782B2 (en) 2006-08-18 2014-08-05 Commonwealth Scientific And Industrial Research Organisation Polymeric coatings and methods for forming them
KR20090086235A (en) * 2006-10-31 2009-08-11 에스알유 바이오시스템즈, 인코포레이티드 Method for blocking non-specific protein binding on a functionalized surface
US7854941B2 (en) * 2007-02-12 2010-12-21 The University Of Southern Mississippi Method of attaching drug compounds to non-reactive polymer surfaces
US8597630B2 (en) * 2007-04-19 2013-12-03 University Of Massachusetts Thermal-responsive polymer networks, compositions, and methods and applications related thereto
US20100286343A1 (en) * 2008-01-08 2010-11-11 Thomas Burghardt Surfaces containing coupling activator compounds and reinforced composites produced therefrom
US20110045275A1 (en) 2008-01-08 2011-02-24 Rajappa Tadepalli Fibers treated with polymerization compounds and fiber reinforced composites made therefrom
US8852732B2 (en) 2008-01-08 2014-10-07 Johns Manville Fiber-reinforced composite articles made from fibers having coupling-initiator compounds and methods of making the articles
US8378094B2 (en) * 2008-01-08 2013-02-19 Johns Manville Polymerization initiators for fiber-reinforced polymer composites and materials made from the composites
JP2009213661A (en) * 2008-03-10 2009-09-24 National Univ Corp Shizuoka Univ Method of manufacturing medical instrument
US8682408B2 (en) 2008-03-28 2014-03-25 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8583204B2 (en) 2008-03-28 2013-11-12 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8613834B2 (en) 2008-04-03 2013-12-24 Basf Se Paper coating or binding formulations and methods of making and using same
CN102203173B (en) 2008-09-19 2014-04-02 3M创新有限公司 Ligand graft functionalized substrates
EP2326944A4 (en) 2008-09-19 2013-11-13 Dexcom Inc Particle-containing membrane and particulate electrode for analyte sensors
JP2012509365A (en) 2008-11-17 2012-04-19 ディーエスエム アイピー アセッツ ビー.ブイ. Surface modification of polymers by surfactants and reactive end groups
JP6150267B2 (en) * 2008-12-05 2017-06-21 アロー インターナショナル インコーポレイテッド Anti-thrombogenic graft antimicrobial in non-fouling - Fromm composition
WO2010065958A1 (en) * 2008-12-05 2010-06-10 Semprus Biosciences Corp. Layered non-fouling, antimicrobial, antithrombogenic coatings
US8691983B2 (en) 2009-03-03 2014-04-08 Innovative Surface Technologies, Inc. Brush polymer coating by in situ polymerization from photoreactive surface
TWI402300B (en) * 2009-03-09 2013-07-21 Univ Nat Sun Yat Sen Method for patterning polymer surface
FR2954327B1 (en) * 2009-12-23 2012-11-30 Valois Sas surface treatment method for a fluid dispensing device.
FR2954330B1 (en) * 2009-12-23 2013-01-04 Valois Sas surface treatment method for a fluid dispensing device.
FR2954329B1 (en) * 2009-12-23 2013-01-18 Valois Sas surface processing method elastomer of a fluid dispensing device.
FR2954326B1 (en) * 2009-12-23 2013-01-18 Valois Sas surface treatment method for a fluid dispensing device.
FR2954328B1 (en) * 2009-12-23 2013-01-18 Valois Sas surface treatment method for a fluid dispensing device.
US8945156B2 (en) 2010-05-19 2015-02-03 University Of Utah Research Foundation Tissue fixation
US8858577B2 (en) 2010-05-19 2014-10-14 University Of Utah Research Foundation Tissue stabilization system
EP2579905A4 (en) 2010-06-09 2016-03-23 Arrow Int Inc Articles having non-fouling surfaces and processes for preparing the same including pretreatment of substrates
JP6083071B2 (en) * 2010-06-09 2017-02-22 アロー インターナショナル インコーポレイテッド Non-staining, antimicrobial, antithrombotic grafting from compositions
CA2799786A1 (en) 2010-06-09 2011-12-15 Semprus Biosciences Corp. Non-fouling, anti-microbial, anti-thrombogenic graft compositions
WO2012047755A2 (en) * 2010-10-06 2012-04-12 Ast Products, Inc. Functionalized hydrophilic and lubricious polymeric matrix and methods of using same
US10238776B2 (en) 2010-12-29 2019-03-26 St. Jude Medical, Atrial Fibrillation Division, Inc. Hydrophobic catheter and composition
US8852214B2 (en) 2011-02-04 2014-10-07 University Of Utah Research Foundation System for tissue fixation to bone
EP2716669B1 (en) 2011-06-03 2018-11-07 Sumitomo Rubber Industries, Ltd. Tire and gasket for syringes
US8487017B2 (en) 2011-06-27 2013-07-16 Covidien Lp Biodegradable materials for orthopedic devices based on polymer stereocomplexes
US9120119B2 (en) 2011-12-14 2015-09-01 Semprus Biosciences Corporation Redox processes for contact lens modification
WO2013115917A1 (en) 2011-12-14 2013-08-08 Semprus Biosciences Corp. Imbibing process for contact lens surface modification
EP2791223A4 (en) 2011-12-14 2015-11-18 Semprus Biosciences Corp Surface modified contact lenses
JP2015500913A (en) 2011-12-14 2015-01-08 センプラス・バイオサイエンシーズ・コーポレイションSemprus Biosciences Corp. Multi-step uv method for producing a surface modifying contact lenses
AU2012351980B2 (en) 2011-12-14 2015-09-17 Arrow International, Inc. Silicone hydrogel contact lens modified using Lanthanide or Transition metal oxidants
JP5763565B2 (en) 2012-02-02 2015-08-12 住友ゴム工業株式会社 Surface modification method and a surface modification elastic body
US8545951B2 (en) 2012-02-29 2013-10-01 Kimberly-Clark Worldwide, Inc. Endotracheal tubes and other polymer substrates including an anti-fouling treatment
JP5812935B2 (en) 2012-05-16 2015-11-17 住友ゴム工業株式会社 Surface modification method and a surface modification elastic body
US9629632B2 (en) 2012-07-30 2017-04-25 Conextions, Inc. Soft tissue repair devices, systems, and methods
US10219804B2 (en) 2012-07-30 2019-03-05 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
US9427309B2 (en) 2012-07-30 2016-08-30 Conextions, Inc. Soft tissue repair devices, systems, and methods
KR101438270B1 (en) * 2012-08-03 2014-09-05 동국대학교 산학협력단 Surface treatment method of polymer medical device for biofilm prevention and thereof
WO2014038688A1 (en) * 2012-09-10 2014-03-13 住友ゴム工業株式会社 Surface modification method and surface-modified elastic body
JP2014065022A (en) 2012-09-27 2014-04-17 Toshiba Corp Desalination treatment membrane
JP5620456B2 (en) 2012-11-20 2014-11-05 住友ゴム工業株式会社 Surface modification method and a surface modification elastic body
JP6053482B2 (en) 2012-11-30 2016-12-27 住友ゴム工業株式会社 Method of manufacturing the syringes gasket
JP6105292B2 (en) 2013-01-07 2017-03-29 住友ゴム工業株式会社 Surface modification method and a surface modification elastic body
US9913933B2 (en) 2013-03-15 2018-03-13 St. Jude Medical, Cardiology Division, Inc. Multilayered catheter shaft containing polyvinylidene fluoride polymers
JP5816222B2 (en) 2013-04-25 2015-11-18 住友ゴム工業株式会社 Surface modification method and a surface modification elastic body
US9845406B2 (en) * 2013-05-09 2017-12-19 Terry Cassaday Method and composition re polyurethane seating
JP5797239B2 (en) 2013-06-11 2015-10-21 住友ゴム工業株式会社 Surface modification method and syringes gasket three-dimensional object
JP6214583B2 (en) * 2014-03-04 2017-10-18 ダイキン工業株式会社 Polymeric substrate, its use and a method of manufacturing the same
JP6338504B2 (en) 2014-10-02 2018-06-06 住友ゴム工業株式会社 Surface modification method and a surface modification elastic body
JP6259392B2 (en) * 2014-12-26 2018-01-10 住友ゴム工業株式会社 Method for modifying the surface modified rubber or surface modifying thermoplastic elastomer and rubber or thermoplastic elastomer surface
CN104497214B (en) * 2015-01-19 2017-04-26 北京石油化工学院 Preparation of solid phase synthesis method based on the whole polymer medium material
JP2017031339A (en) * 2015-08-03 2017-02-09 住友ゴム工業株式会社 Surface modification method and surface modified body
CN105837734A (en) * 2016-05-09 2016-08-10 上海惠昌化工厂 Organosilicone modified acrylic polyester potash, preparation method and application to cancer prevention and treatment
CN106119820B (en) * 2016-06-01 2018-06-22 华南理工大学 Controllable method using grafting techniques to improve the blood compatibility of material surfaces

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4539061A (en) * 1983-09-07 1985-09-03 Yeda Research And Development Co., Ltd. Process for the production of built-up films by the stepwise adsorption of individual monolayers
US5128170A (en) * 1989-05-11 1992-07-07 Kanegafunchi Kagaku Kogyo Kabushiki Kaisha Method for manufacturing medical device having a highly biocompatible surface
US5258454A (en) * 1988-09-01 1993-11-02 Riso National Laboratory Peptide synthesis method and solid support for use in the method
US5290548A (en) * 1987-04-10 1994-03-01 University Of Florida Surface modified ocular implants, surgical instruments, devices, prostheses, contact lenses and the like
US5491097A (en) * 1989-06-15 1996-02-13 Biocircuits Corporation Analyte detection with multilayered bioelectronic conductivity sensors
US5800412A (en) * 1996-10-10 1998-09-01 Sts Biopolymers, Inc. Hydrophilic coatings with hydrating agents
US5804263A (en) * 1990-10-24 1998-09-08 University Of Florida Research Foundation, Inc. Combined plasma and gamma radiation polymerization method for modifying surfaces
US5858653A (en) * 1997-09-30 1999-01-12 Surmodics, Inc. Reagent and method for attaching target molecules to a surface
US5948621A (en) * 1997-09-30 1999-09-07 The United States Of America As Represented By The Secretary Of The Navy Direct molecular patterning using a micro-stamp gel
US6040138A (en) * 1995-09-15 2000-03-21 Affymetrix, Inc. Expression monitoring by hybridization to high density oligonucleotide arrays
US6087102A (en) * 1998-01-07 2000-07-11 Clontech Laboratories, Inc. Polymeric arrays and methods for their use in binding assays
US6121027A (en) * 1997-08-15 2000-09-19 Surmodics, Inc. Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups
US6174683B1 (en) * 1999-04-26 2001-01-16 Biocept, Inc. Method of making biochips and the biochips resulting therefrom
US6225625B1 (en) * 1989-06-07 2001-05-01 Affymetrix, Inc. Signal detection methods and apparatus
US6232066B1 (en) * 1997-12-19 2001-05-15 Neogen, Inc. High throughput assay system
US6287285B1 (en) * 1998-01-30 2001-09-11 Advanced Cardiovascular Systems, Inc. Therapeutic, diagnostic, or hydrophilic coating for an intracorporeal medical device
US6319674B1 (en) * 1999-09-16 2001-11-20 Agilent Technologies, Inc. Methods for attaching substances to surfaces
US6368587B1 (en) * 1997-06-28 2002-04-09 Huels Aktiengesellschaft Bioactive surface coating using macroinitiators

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4377010A (en) * 1978-11-08 1983-03-22 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Biocompatible material comprising a base polymer bulk graft polymerized with an ethylenically unsaturated carboxylic acid
US4331697A (en) 1980-09-02 1982-05-25 Teijin Limited Novel heparin derivative, method for production thereof, and method for rendering biomedical materials antithrombotic by use of the novel heparin derivative
US4589964A (en) * 1980-10-08 1986-05-20 American Hospital Supply Corporation Process for graft copolymerization of a pre-formed substrate
US4442133A (en) 1982-02-22 1984-04-10 Greco Ralph S Antibiotic bonding of vascular prostheses and other implants
US5002582A (en) 1982-09-29 1991-03-26 Bio-Metric Systems, Inc. Preparation of polymeric surfaces via covalently attaching polymers
US5512329A (en) * 1982-09-29 1996-04-30 Bsi Corporation Substrate surface preparation
JPS6351035B2 (en) * 1984-04-27 1988-10-12 Yoshito Ikada
US4978481A (en) * 1989-01-13 1990-12-18 Ciba-Geigy Corporation Process for the encapsulation of preformed substrates by graft copolymerization
US5525348A (en) 1989-11-02 1996-06-11 Sts Biopolymers, Inc. Coating compositions comprising pharmaceutical agents
US5069899A (en) 1989-11-02 1991-12-03 Sterilization Technical Services, Inc. Anti-thrombogenic, anti-microbial compositions containing heparin
US5211993A (en) 1990-12-10 1993-05-18 Advanced Surface Technology, Inc. Method of making novel separation media
GB9118597D0 (en) * 1991-08-30 1991-10-16 Biocompatibles Ltd Polymer treatments
US5355832A (en) 1992-12-15 1994-10-18 Advanced Surface Technology, Inc. Polymerization reactor
US5663237A (en) 1995-06-15 1997-09-02 The University Of Akron Graft copolymerization in supercritical media
US5607475A (en) * 1995-08-22 1997-03-04 Medtronic, Inc. Biocompatible medical article and method
US6013855A (en) 1996-08-06 2000-01-11 United States Surgical Grafting of biocompatible hydrophilic polymers onto inorganic and metal surfaces
AT201031T (en) * 1997-04-14 2001-05-15 Degussa A method for modifying the surface of polymer substrates by grafting polymerization
JP3139410B2 (en) * 1997-04-15 2001-02-26 富士ゼロックス株式会社 Graft polymerization process
DE19727554A1 (en) * 1997-06-28 1999-01-07 Huels Chemische Werke Ag A method for hydrophilizing the surface of polymeric substrates with a macroinitiator as primers

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4539061A (en) * 1983-09-07 1985-09-03 Yeda Research And Development Co., Ltd. Process for the production of built-up films by the stepwise adsorption of individual monolayers
US5290548A (en) * 1987-04-10 1994-03-01 University Of Florida Surface modified ocular implants, surgical instruments, devices, prostheses, contact lenses and the like
US5258454A (en) * 1988-09-01 1993-11-02 Riso National Laboratory Peptide synthesis method and solid support for use in the method
US5128170A (en) * 1989-05-11 1992-07-07 Kanegafunchi Kagaku Kogyo Kabushiki Kaisha Method for manufacturing medical device having a highly biocompatible surface
US6225625B1 (en) * 1989-06-07 2001-05-01 Affymetrix, Inc. Signal detection methods and apparatus
US5491097A (en) * 1989-06-15 1996-02-13 Biocircuits Corporation Analyte detection with multilayered bioelectronic conductivity sensors
US5804263A (en) * 1990-10-24 1998-09-08 University Of Florida Research Foundation, Inc. Combined plasma and gamma radiation polymerization method for modifying surfaces
US6040138A (en) * 1995-09-15 2000-03-21 Affymetrix, Inc. Expression monitoring by hybridization to high density oligonucleotide arrays
US5800412A (en) * 1996-10-10 1998-09-01 Sts Biopolymers, Inc. Hydrophilic coatings with hydrating agents
US6368587B1 (en) * 1997-06-28 2002-04-09 Huels Aktiengesellschaft Bioactive surface coating using macroinitiators
US6121027A (en) * 1997-08-15 2000-09-19 Surmodics, Inc. Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups
US5948621A (en) * 1997-09-30 1999-09-07 The United States Of America As Represented By The Secretary Of The Navy Direct molecular patterning using a micro-stamp gel
US5858653A (en) * 1997-09-30 1999-01-12 Surmodics, Inc. Reagent and method for attaching target molecules to a surface
US6232066B1 (en) * 1997-12-19 2001-05-15 Neogen, Inc. High throughput assay system
US6087102A (en) * 1998-01-07 2000-07-11 Clontech Laboratories, Inc. Polymeric arrays and methods for their use in binding assays
US6287285B1 (en) * 1998-01-30 2001-09-11 Advanced Cardiovascular Systems, Inc. Therapeutic, diagnostic, or hydrophilic coating for an intracorporeal medical device
US6174683B1 (en) * 1999-04-26 2001-01-16 Biocept, Inc. Method of making biochips and the biochips resulting therefrom
US6319674B1 (en) * 1999-09-16 2001-11-20 Agilent Technologies, Inc. Methods for attaching substances to surfaces

Cited By (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080183152A1 (en) * 2001-01-12 2008-07-31 Issam Raad Medical devices with broad spectrum antimicrobial activity
US7651661B2 (en) 2001-01-12 2010-01-26 Board Of Regents, The University Of Texas System Medical devices with broad spectrum antimicrobial activity
US8313760B2 (en) 2002-05-24 2012-11-20 Angiotech International Ag Compositions and methods for coating medical implants
US8425927B2 (en) 2002-05-24 2013-04-23 Angiotech International Ag Compositions and methods for coating medical implants
US20080089952A1 (en) * 2002-05-24 2008-04-17 Angiotech International Ag Compositions and methods for coating medical implants
US8372420B2 (en) 2002-05-24 2013-02-12 Angiotech International Ag Compositions and methods for coating medical implants
US20070270447A1 (en) * 2002-05-24 2007-11-22 Angiotech International Ag Compositions and methods for coating medical implants
US20040071912A1 (en) * 2002-09-25 2004-04-15 Berth Jorgen Mikael Method for improving fire resistance of polyethylene tubing and polyethylene tubing manufactured according to said method
US6869997B2 (en) * 2003-05-06 2005-03-22 Arkema, Inc. Polymerization of fluoromonomers using a 3-allyloxy-2-hydroxy-1-propanesulfonic acid salt as surfactant
US20040225053A1 (en) * 2003-05-06 2004-11-11 Atofina Chemicals, Inc. Polymerization of fluoromonomers using a 3-allyloxy-2-hydroxy-1-propanesulfonic acid salt as surfactant
US9078441B2 (en) 2003-06-06 2015-07-14 Board Of Regents, The University Of Texas System Antimicrobial flush solutions
US20050013836A1 (en) * 2003-06-06 2005-01-20 Board Of Regents, The University Of Texas System Antimicrobial flush solutions
US20100055086A1 (en) * 2003-06-06 2010-03-04 Issam Raad Antimicrobial Flush Solutions
US8709342B2 (en) 2003-06-06 2014-04-29 Board Of Regents, The University Of Texas System Antimicrobial flush solutions
US7601731B2 (en) 2003-06-06 2009-10-13 Board Of Regents, The University Of Texas System Antimicrobial flush solutions
US20110201692A1 (en) * 2003-06-06 2011-08-18 The Board Of Regents Of The University Of Texas System Antimicrobial flush solutions
US20070106232A1 (en) * 2003-06-16 2007-05-10 Rider Ii Deal L Method and apparatus for extending feeding tube longevity
US20060142339A1 (en) * 2003-06-19 2006-06-29 Bosmans Jean-Paul R M Aminosulfonyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht 4-antagonists
US9421091B2 (en) 2003-06-27 2016-08-23 Abbott Medical Optics Inc. IOL insertion apparatus
US20040267359A1 (en) * 2003-06-27 2004-12-30 Harish Makker IOL insertion apparatus and methods for making and using same
US20100129523A1 (en) * 2003-06-27 2010-05-27 Abbot Medical Optic Inc. Iol insertion apparatus and methods for making and using same
US8956684B2 (en) 2003-06-27 2015-02-17 Abbott Medical Optics Inc. IOL insertion apparatus and methods for making and using same
US20050197634A1 (en) * 2004-01-20 2005-09-08 Board Of Regents, The University Of Texas System Methods for coating and impregnating medical devices with antiseptic compositions
US8298565B2 (en) 2005-07-15 2012-10-30 Micell Technologies, Inc. Polymer coatings containing drug powder of controlled morphology
US20090123515A1 (en) * 2005-07-15 2009-05-14 Doug Taylor Polymer coatings containing drug powder of controlled morphology
US20090062909A1 (en) * 2005-07-15 2009-03-05 Micell Technologies, Inc. Stent with polymer coating containing amorphous rapamycin
US9827117B2 (en) 2005-07-15 2017-11-28 Micell Technologies, Inc. Polymer coatings containing drug powder of controlled morphology
US8758429B2 (en) 2005-07-15 2014-06-24 Micell Technologies, Inc. Polymer coatings containing drug powder of controlled morphology
US9737645B2 (en) 2006-04-26 2017-08-22 Micell Technologies, Inc. Coatings containing multiple drugs
US9415142B2 (en) 2006-04-26 2016-08-16 Micell Technologies, Inc. Coatings containing multiple drugs
US8852625B2 (en) 2006-04-26 2014-10-07 Micell Technologies, Inc. Coatings containing multiple drugs
US8636767B2 (en) 2006-10-02 2014-01-28 Micell Technologies, Inc. Surgical sutures having increased strength
US20100030261A1 (en) * 2006-10-02 2010-02-04 Micell Technologies, Inc. Surgical Sutures Having Increased Strength
US9539593B2 (en) 2006-10-23 2017-01-10 Micell Technologies, Inc. Holder for electrically charging a substrate during coating
WO2008060522A3 (en) * 2006-11-10 2008-07-10 Univ California Atmospheric pressure plasma-induced graft polymerization
US9144824B2 (en) 2006-11-10 2015-09-29 The Regents Of The University Of California Atmospheric pressure plasma-induced graft polymerization
US20100035074A1 (en) * 2006-11-10 2010-02-11 Yoram Cohen Atmospheric pressure plasma-induced graft polymerization
US9737642B2 (en) 2007-01-08 2017-08-22 Micell Technologies, Inc. Stents having biodegradable layers
US9433516B2 (en) 2007-04-17 2016-09-06 Micell Technologies, Inc. Stents having controlled elution
US9486338B2 (en) 2007-04-17 2016-11-08 Micell Technologies, Inc. Stents having controlled elution
US9775729B2 (en) 2007-04-17 2017-10-03 Micell Technologies, Inc. Stents having controlled elution
US8900651B2 (en) 2007-05-25 2014-12-02 Micell Technologies, Inc. Polymer films for medical device coating
US20090326165A1 (en) * 2007-09-25 2009-12-31 Patil Damodar R Method of making graft copolymers from sodium poly(aspartate) and the resulting graft copolymer
US7999040B2 (en) 2007-09-25 2011-08-16 Nanochem Solutions, Inc. Method of making graft copolymers from sodium poly(aspartate) and the resulting graft copolymer
US9789233B2 (en) 2008-04-17 2017-10-17 Micell Technologies, Inc. Stents having bioabsorbable layers
US9981071B2 (en) 2008-07-17 2018-05-29 Micell Technologies, Inc. Drug delivery medical device
US9486431B2 (en) 2008-07-17 2016-11-08 Micell Technologies, Inc. Drug delivery medical device
US9510856B2 (en) 2008-07-17 2016-12-06 Micell Technologies, Inc. Drug delivery medical device
US8834913B2 (en) 2008-12-26 2014-09-16 Battelle Memorial Institute Medical implants and methods of making medical implants
US8524097B2 (en) 2009-03-18 2013-09-03 Medtronic, Inc. Plasma deposition to increase adhesion
US20100236684A1 (en) * 2009-03-18 2010-09-23 Greg Garlough Plasma deposition to increase adhesion
US8361334B2 (en) 2009-03-18 2013-01-29 Medtronic, Inc. Plasma deposition to increase adhesion
US20100237043A1 (en) * 2009-03-18 2010-09-23 Greg Garlough Plasma deposition to increase adhesion
WO2010111232A3 (en) * 2009-03-23 2011-04-21 Micell Technologies, Inc. Drug delivery medical device
US9981072B2 (en) 2009-04-01 2018-05-29 Micell Technologies, Inc. Coated stents
US20100255239A1 (en) * 2009-04-03 2010-10-07 Hammond Terry E Ultraviolet radiation curable pressure sensitive acrylic adhesive
US8974680B2 (en) * 2009-09-25 2015-03-10 Kabushiki Kaisha Toshiba Pattern forming method
US20120228262A1 (en) * 2009-09-25 2012-09-13 Kabushiki Kaisha Toshiba Pattern forming method
US9190288B2 (en) 2009-09-25 2015-11-17 Kabushiki Kaisha Toshiba Pattern forming method
US9687864B2 (en) 2010-03-26 2017-06-27 Battelle Memorial Institute System and method for enhanced electrostatic deposition and surface coatings
US8795762B2 (en) 2010-03-26 2014-08-05 Battelle Memorial Institute System and method for enhanced electrostatic deposition and surface coatings
US10232092B2 (en) 2010-04-22 2019-03-19 Micell Technologies, Inc. Stents and other devices having extracellular matrix coating
US10117972B2 (en) 2011-07-15 2018-11-06 Micell Technologies, Inc. Drug delivery medical device
US10188772B2 (en) 2011-10-18 2019-01-29 Micell Technologies, Inc. Drug delivery medical device
US9795762B2 (en) 2011-12-14 2017-10-24 Arrow International, Inc. Surface modification for dialysis catheters
AU2016200311B2 (en) * 2011-12-14 2017-06-29 Arrow International, Inc. Luminal modifications for catheters
US9902830B2 (en) 2015-02-04 2018-02-27 Alltech, Inc. Aflatoxin templates, molecularly imprinted polymers, and methods of making and using the same

Also Published As

Publication number Publication date
WO2001017575A1 (en) 2001-03-15
JP2003510378A (en) 2003-03-18
EP1214107A1 (en) 2002-06-19
US6358557B1 (en) 2002-03-19
AU6520600A (en) 2001-04-10

Similar Documents

Publication Publication Date Title
EP0410357B1 (en) Membrane having hydrophilic surface
EP0862858B1 (en) Process for preparing antimicrobial plastics
US7087658B2 (en) Water-soluble coating agents bearing initiator groups
US6709706B2 (en) Hydrophilic coating and substrates coated therewith having enhanced durablity and lubricity
JP4920414B2 (en) Medical device and a manufacturing method thereof lubricious coating surface
EP1153964B2 (en) Surface-treated optical article of plastics material and method of surface treatment
DE60214513T2 (en) A process for the surface modification
US5217802A (en) Hydrophobic polymeric membrane composites
EP1549689B1 (en) A hydrogel
KR100660758B1 (en) Biomedical devices and contact lens having at least one surfaces having a coating and a method for manufacturing the devices
US5620738A (en) Non-reactive lubicious coating process
CN1938224B (en) Method for treating surface of base, surface-treated base, material and instrument for medical use
US4267202A (en) Method for modifying the surface properties of polymer substrates
EP0517890B1 (en) Biocompatible abrasion resistant coated substrates
US5538512A (en) Lubricious flow directed catheter
US5443455A (en) Guidewire and method of pretreating metal surfaces for subsequent polymer coating
JP4267086B2 (en) Method for producing a molded article having a wettable surface made from latent hydrophilic monomer
US4978481A (en) Process for the encapsulation of preformed substrates by graft copolymerization
EP0651005B1 (en) Lubricious silicone surface modification
US20020193885A1 (en) Prostheses for plastic reconstruction with improved hydrophilicity properties, and method for obtaining them
CN1096352C (en) Molded polymer article having hydrophilic surface and process for producing the same
US4943460A (en) Process for coating polymer surfaces and coated products produced using such process
EP0217771B1 (en) Method of forming an improved hydrophilic coating on a polymer surface
Gupta et al. Plasma-induced graft polymerization of acrylic acid onto poly (ethylene terephthalate) films: characterization and human smooth muscle cell growth on grafted films
JP4316683B2 (en) Hydrophilic coating and a method of manufacturing the same

Legal Events

Date Code Title Description
AS Assignment

Owner name: STS BIOPOLYMERS, INC., NEW YORK

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WANG, GUO-BIN;ZHANG, XIANPING;REEL/FRAME:012443/0053;SIGNING DATES FROM 19991112 TO 19991115

AS Assignment

Owner name: CREDIT SUISSE, AS COLLATERAL AGENT, NEW YORK

Free format text: SECURITY AGREEMENT;ASSIGNOR:ANGIOTECH BIOCOATINGS CORP.;REEL/FRAME:017448/0708

Effective date: 20060323

AS Assignment

Owner name: ANGIOTECH BIOCOATINGS CORP., NEW YORK

Free format text: CHANGE OF NAME;ASSIGNOR:STS BIOPOLYMERS, INC.;REEL/FRAME:017869/0231

Effective date: 20041021

AS Assignment

Owner name: ANGIOTECH BIOCOATINGS, INC., NEW YORK

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:CREDIT SUISSE;REEL/FRAME:018606/0632

Effective date: 20061211

AS Assignment

Owner name: ANGIOTECH BIOCOATINGS CORP., NEW YORK

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED ON REEL 018606 FRAME 0632;ASSIGNOR:CREDIT SUISSE;REEL/FRAME:018633/0599

Effective date: 20061211

Owner name: ANGIOTECH BIOCOATINGS CORP., NEW YORK

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED ON REEL 018606 FRAME 0632. ASSIGNOR(S) HEREBY CONFIRMS THE RELEASE OF SECURITY INTEREST;ASSIGNOR:CREDIT SUISSE;REEL/FRAME:018633/0599

Effective date: 20061211