JP2010512815A - Coatings prepared from poly (ethylene oxide) and photoinitiator containing backbone - Google Patents

Abstract

  The application relates to at least 50% by weight of one or more polymer components, optionally combined with the following a) and b): a) one or more non-thermoplastic hydrophilic polymers Or two or more poly (ethylene oxide); and b) one or more low molecular weight skeletons that are covalently bonded to and / or covalently linked to the low molecular weight skeleton. Having a plurality of photoinitiator moieties introduced (the photoinitiator part is one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and one or more of the above Preparation of a medical device comprising a coating composition comprising (comprising 0.01 to 20% by weight of the total amount of low molecular weight skeleton) (extruded, injection molded or powder coated, then UV or visible light It discloses a method for crosslinking to) by morphism. This application is an extruded, injection molded or powder coated medical device on which poly (ethylene oxide) (PEO), an optional non-thermoplastic hydrophilic polymer, and a plurality of photoinitiators Further disclosed is a medical device having a layer of a coating composition that is covalently crosslinked with a low molecular weight backbone having a residue of an agent moiety.

Description

  The present invention relates to a method for preparing a medical device element using extrusion, injection molding or powder coating. The invention further relates to an extruded, injection molded or powder coated medical device element. The medical device element is a prefabricated shaped article or thermoplastic base polymer on which a poly (ethylene oxide) (PEO) covalently crosslinked coating composition, optionally non-thermoplastic Characterized by hydrophilic polymers and those having a low molecular weight backbone layer having residues of a plurality of photoinitiator moieties covalently bonded to and / or covalently introduced into PEO.

  Medical devices often require a smooth surface. In the medical field, simple devices such as catheters, guidewires, etc. must be inserted into body cavities or through the skin and later withdrawn. Patient therapy often includes catheterization procedures or nutrient delivery systems, most of which involve invasive techniques. In all of the above cases, lubricity that is completely stable during both the insertion and withdrawal phases of the procedure significantly contributes to patient comfort.

U.S. Pat. No. 5,084,315 discloses a method of preparing a shaped article, such as by coextrusion utilizing a composition comprising PEO and polyurethane that are not covalently crosslinked. The surface of the product is said to be smooth when in contact with water.
US Pat. No. 6,447,835 discloses a method for preparing coated hollow high molecular weight tubular elements for medical devices by co-extruding the tube with the coating. The coating can include poly (ethylene oxide).

The coating can also include an acrylic monomer that can be reacted to form a crosslinked acrylic polymer network after extrusion.
U.S. Pat. No. 4,684,558 discloses a method for producing an adhesively crosslinked poly (ethylene oxide) hydrogel sheet by crosslinking with electron radiation.

US Pat. No. 6,790,519 and WO 2005/079883 describe crosslinked poly (ethylene oxide) hydrogels by grafting silanol-containing moieties onto poly (ethylene oxide) chains. A method for manufacturing is disclosed. Cross-linking between poly (ethylene oxide) chains occurs by a condensation reaction between silanol groups.
U.S. Pat. No. 7,276,247 discloses a pendant photoinitiator on another poly (ethylene oxide) chain, which allows UV irradiation of unsaturated functional groups present in the poly (ethylene oxide) chain. A method for crosslinking is disclosed.

  International Publication Nos. 03/086493 and 2005/092402 include a photoinitiator and an unsaturated functional group present as terminal groups in a poly (ethylene oxide) chain. A method is disclosed for crosslinking by UV irradiation of unsaturated functional groups present in.

  WO 2005/035607 has pendant photoinitiators on other poly (ethylene oxide) chains and is crosslinked using UV irradiation of unsaturated functional groups present in the poly (ethylene oxide) chains. Further disclosed is a method for producing a hydrophilic poly (ethylene oxide) composition prepared by processing.

  The above-mentioned prior art documents mainly solve the problem of crosslinking of poly (ethylene oxide) using radical polymerization of unsaturated functional groups.

  The present invention provides an alternative route comprising the application of a particular skeleton having a plurality of photoinitiator moieties covalently attached to and / or covalently introduced into the skeleton. I will provide a. Thus, the present invention provides a method for the preparation of a medical device that provides an advantage with respect to simplicity and offers advantages with respect to very low friction, excellent cohesion and good adhesion.

Thus, the present invention includes poly (ethylene oxide) and a low molecular weight skeleton that is covalently bonded to and / or covalently introduced into the low molecular weight skeleton. A method for preparing a medical device element is provided (see claim 1).
Furthermore, the present invention also provides various medical devices as claimed in claims 12, 13 and 14.

FIG. 1 illustrates a prefabricated tube medical device (eg, a catheter tube), a layer of thermoplastic base polymer, and a covalently crosslinked coating composition.

[Method of the present invention]
As mentioned above, the present invention relates to a method for the preparation of a medical device element, which method comprises the following steps;
(I) providing a prefabricated shaped article and / or a thermoplastic base polymer;
(Ii) providing a coating composition comprising:
(A) one or more poly (ethylene oxide) as only one or more polymer components, optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein the one or more Two or more poly (ethylene oxide) comprises at least 50% by weight of the one or more polymer components, and (b) one or more low molecular weight skeletons shared by the low molecular weight skeletons A low molecular weight skeleton having a plurality of photoinitiator moieties attached and / or covalently introduced into the low molecular weight skeleton, wherein the photoinitiator moiety is one or more of the above Comprising from 0.01 to 20% by weight of the total amount of poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and one or more low molecular weight skeletons;
(Iii) A coating composition of step (ii) is applied in advance on top of the pre-fabricated shaped article and / or thermoplastic substrate polymer of step (i) and having a layer of the coating composition thereon Extruding, injection molding or powder coating to provide a fabricated shaped article and / or a medical device element of the substrate polymer, wherein the prefabricated shaped article and the substrate. If both polymers are present, the pre-fabricated shaped article has a layer of the base polymer on it;
(Iv) irradiating the coating composition with UV or visible light to covalently crosslink the coating composition.

  In a first major aspect of the present invention, the one or more poly (ethylene oxides) are the sole or multiple polymer components of the coating composition.

  The present invention relates to a medical where the crosslinking of a specific coating composition after extrusion, injection molding or powder coating using one or more photoinitiators and UV or visible light comprises: Based on finding to provide a device element: good adhesion of the coating composition (including poly (ethylene oxide) (PEO)) to the pre-fabricated shaped article or substrate polymer; Good cohesive strength of the coating composition; and good water retention of poly (ethylene oxide) (PEO) and any non-thermoplastic hydrophilic polymer in the wet state, and thereby excellent properties with long-term low friction. Compared to the majority of previously known methods, the present invention is completely independent of polymerization and crosslinking using ethylenically unsaturated moieties (eg, acrylate, methacrylate or vinyl moieties); Preferably, the product is completely devoid of any ethylenically unsaturated moieties, particularly acrylate, methacrylate and vinyl moieties.

  The good properties for good water retention and good long-term low friction properties of the coating are that the cross-linking of the polymer and fixation to the base polymer or pre-fabricated shaped article, Somewhat contradict the fact that flexibility is limited. However, due to the thermoplastic nature of PEO, along with high hydrophilicity and friction reducing properties, PEO is particularly suitable for the present invention and the products of the present invention. Furthermore, the presence of a photoinitiator moiety that is covalently and / or covalently introduced into the backbone further promotes the useful properties described above.

[Medical device]
The term “medical device” should be described in a fairly broad sense. Suitable examples of medical devices (including equipment) include catheters (eg, urinary catheters), endoscopes, laryngoscopes, supply tubes, drainage tubes, endotracheal tubes, guide wires, sutures, cannulas, Needles, thermometers, condoms, urisheaths, barrier coatings such as for the following applications, gloves, stents and other implants, contact lenses, extracorporeal blood conduits, membranes such as for the following applications, dialysis, blood Filters, circulatory assist devices, condoms, trauma dressings and stoma bags. Most relevant are catheters, endoscopes, laryngoscopes, supply tubes, drainage tubes, guide wires, sutures, and stents and other implants. A medical device of particular interest in the context of the present invention is a catheter, for example a urinary catheter.

  Non-medical applications such as packaging for foodstuffs, razor blades, fishing nets, conduits for wiring, water pipes with internal coatings, sports products, cosmetic additives, mold release agents, and fishing lines It is also envisioned that it will be equally useful for the preparation of devices having low friction surfaces for meshes. Thus, in yet another aspect of the present invention, the methods and devices described herein and described in the claims can be modified to cover the above possibilities.

  Some medical devices are referred to as ready-to-use medical devices that can be composed of one or more medical device elements that can be assembled or repositioned. Reference to “medical device element” and “catheter element” means the medical device or catheter itself (ie, a single medical device or catheter) or a “ready-to-use” medical device or catheter.

  In the context of the present invention, the medical device element is formed from a prefabricated shaped article and / or a thermoplastic base polymer and a coating composition. During (simultaneous) or subsequent application of the coating composition by co-extrusion, injection molding or powder coating of the prefabricated shaped article and / or the thermoplastic base polymer, and co-extrusion, injection molding or powder coating, At least a part of the surface of the prefabricated shaped article or the thermoplastic base polymer starts to be coated with the coating composition as described in more detail below. In some embodiments, the coating composition (i.e., hydrophilic coating) is applied to the entire (outer) surface of the pre-fabricated shaped article / substrate polymer, and in some other embodiments. Cover only part of its surface. In the most relevant embodiments, the coating composition covers at least a portion (preferably the entire surface) of the surface of the medical device that is in direct contact (in proper use) with the intended body part of the medical device. .

[Prefabricated product]
In embodiments where a pre-made shaped article is included, the method is designed to provide a coating on the shaped article, for example. A wide variety of shaped articles (eg tubes, wires, lines, stents, catheters, guides, dental and orthodontic instruments, needles, trocars for laparoscopic surgery, laparoscopic accessories, surgical instruments ), And various different materials such as metals and alloys such as stainless steel cores or typical guide-wire alloys such as Ti alloys such as Nitinol and pseudoplastic βTi— A Mo-V-Nb-Al alloy can constitute a shaped article. Furthermore, glass and ceramics, thermoplastic polymers are also envisaged. Suitable materials also include: thermoplastic polymers such as hydrophilic polyurethanes, hydrophobic polyurethanes, polyether block amides (eg Pebax ™), PVC, polyamides, polyesters, biodegradable polyesters, polyacrylates , PS, silicone, latex rubber; block copolymers with various structures, diblock (AB), multiblock (AB) _n or triblock (ABAA), eg SEBS, SIS, SEPS , SBS, SEEPS (the block copolymer can be grafted with maleic anhydride on a rubber block, typically a mid-block for a triblock copolymer); a thermoplastic polymer, for example , LDPE, LLDPE, VLDPE PP, PE, and copolymers of ethylene and propylene, metallocene polymerized polyolefin, PS, EMA, EEA, EnBA, PEg-MAH, EVA, EVOH, and vinyl acetate copolymer grafted with maleic anhydride (EVAg-MAH), or Their (its) combinations, such as Orevac ™ ethylene-vinyl acetate-maleic anhydride terpolymer; and a range of functional polyolefins, eg Lotader ™ ethylene-acrylic acid ester, either MAH or GMA Terpolymers; and maleic anhydride grafted polymers such as PE, PP, PS. Abbreviations are described in the table in the examples.

  There are several strategies to improve surface adhesion between different layers of prefabricated shaped articles and to obtain proper surface adhesion. In some cases, di- or triblock copolymers having one or more polyolefin groups along with one or more polar PS blocks can provide optimal surface adhesion between the layers. Otherwise, the base polymer is modified during the blending of reactive polymers that can utilize functional groups on the polymer, and the nonpolar polymer is mixed with the polar or hydrophilic polymer. Can do. After coextrusion of the coating, a reactive polymer blend is also used during photocuring to improve surface adhesion, and a photoinitiator and a nonpolar, polar or hydrophilic functional polymer. A covalent bond between can be obtained.

[Thermoplastic base polymer]
In embodiments where a thermoplastic substrate polymer is included, the method is designed to apply a coating on the substrate. The thermoplastic base polymer is selected to provide the physical shape of the medical device element or to provide a suitable interface between the coating composition and the pre-fabricated shaped article. . Thus, the base polymer is generally polyurethane, polyether block amide (eg Pebax ™), PVC, polyamide, polyester, polyacrylate, PS, silicone, latex rubber, SEBS, SIS, SEPS, SEEPS, EVA. , PE, and copolymers of ethylene and propylene; thermoplastic polymers such as hydrophilic polyurethane, hydrophobic polyurethane, polyether block amide (eg Pebax ™), PVC, polyamide, polyester, polyacrylate, PS, silicone , latex rubber; various structures diblock (a-B), multiblock (a-B) _n or triblock (a-B-a) block copolymer having, for example, SEBS, SIS, SEPS, SBS, SEE S; the block copolymer can be grafted with maleic anhydride onto a rubber block, typically an intermediate block for a triblock copolymer; thermoplastic polymers such as LDPE, LLDPE, VLDPE, PP, PE and copolymers of ethylene and propylene, metallocene polymerized polyolefins, PS, EMA, EEA, EnBA, PEg-MAH, EVA, EVOH and EVAg-MAH, or combinations thereof, such as Orevac ™ ethylene-vinyl Acetate-maleic anhydride terpolymers; Lotader ™ ethylene-acrylate terpolymers with a range of functional polyolefins, eg, either MAH or GMA; maleic anhydride polymers such as PE, PP, PS, etc. Selected from a fluorinated polymer; and an EPOCROS K-series reactive acrylate-oxazoline copolymer or an RPS / RAS-series styrene-oxazoline copolymer, or a styrene-acrylonitrile-oxazoline copolymer.

  Currently very relevant materials for use as the thermoplastic base polymer are polyurethanes and PVC, in particular polyurethanes, for example hydrophobic polyurethanes.

[Coating composition]
The main component of the coating composition is poly (ethylene oxide) (PEO) (in fact, in the first main aspect of the invention, it is actually the only polymer of the composition) and one or more low molecular weight backbones. And having a plurality of photoinitiator moieties covalently bonded to the low molecular weight skeleton and / or covalently introduced into the low molecular weight skeleton. The one or more poly (ethylene oxides) may be used in the second main aspect of the present invention in combination with one or more non-thermoplastic hydrophilic polymers. These components are discussed in further detail below.

  Depending on the intended use, additives can be introduced into the coating composition to achieve specific properties. For example, one or more additives such as flow aids, matting agents, heat stabilizers, surface cure modifiers, antibacterial agents and osmolality increasing compounds may be added to the coating composition. Can be added. The above additives and their use to improve polymer properties are common and well known to those skilled in the art. The other components can be used in an amount of up to 10%, for example up to 5% by weight of the coating composition.

  The antibacterial agent is a silver salt, such as silver sulfadiazine; an acceptable iodine source, such as povidone iodine (also referred to as PVP iodine); a chlorhexidine salt, such as gluconate, acetate, hydrochloride, etc .; or a salt or It can be a quaternary antibacterial agent, such as benzalkonium chloride or other preservatives or antibiotics. Antibacterial drugs reduce the risk of infection, for example when urodynamic tests are performed.

  In a medical device or device suitable for introduction into a human cavity, an osmolality-raising compound, such as a water-soluble nonionic compound, such as glucose, sorbitol, glycerin, or urea; or an ionic compound, such as It may be advantageous to include alkali metal or alkaline earth metal or silver halides, nitrates, acetates, citrates or benzoates; or carboxylic acids such as acetic acid.

  It may be further desirable to include a plasticizer in the coating composition to facilitate extrusion, injection molding or powder coating. In the above example, the plasticizer can be included in an amount up to 10% by weight of the coating composition. Examples of such plasticizers include carboxylic acid based plasticizers such as partially esterified citric acid available from Jungbunzlauer and citrate esters available from Grindsted Product such as GRINDSTED-CITREM. It should be understood that in the context of the present invention plasticizers should generally be understood as low molecular weight components.

  As will be apparent from the remainder of this specification, the present invention employs the advantages of covalent crosslinking methods that do not require crosslinking with (meth) acrylate monomers, so the most interesting embodiments include (meta ) Does not contain acrylic monomer. Residual acrylates can be very toxic, genotoxic and carcinogenic, or they can cause allergies, skin rashes, sensitization, or locally irritate . Therefore, it is best to avoid systems with residual ethylenically unsaturated monomers, such as acrylates or other reactive monomers.

In one embodiment, the coating composition preferably consists of:
20-99.99 weight percent of one or more poly (ethylene oxide) (PEO);
0-10% by weight of one or more plasticizers;
0.01 to 80% by weight of one or more low molecular weight skeletons: and 0 to 5% by weight of other components.

In a further interesting embodiment, the coating composition consists of:
30-99.9% by weight of one or more poly (ethylene oxide) (PEO);
0-5% by weight of one or more plasticizers,
0.1 to 70% by weight of one or more low molecular weight skeletons; and 0 to 5% by weight of other components.

In certain embodiments, the coating composition consists of:
40-99% by weight of one or more poly (ethylene oxide) (PEO);
1 to 60% by weight of one or more low molecular weight skeletons: and 0 to 5% by weight of other components.

In another specific embodiment, the coating composition consists of:
50-99% by weight of one or more poly (ethylene oxide) (PEO);
0-10% by weight of one or more plasticizers;
1 to 50% by weight of one or more low molecular weight skeletons: and 0 to 5% by weight of other components.

In a further embodiment, the coating composition consists of:
40-94% by weight of one or more poly (ethylene oxide) (PEO);
5-30% by weight of one or more non-thermoplastic hydrophilic polymers;
0-10% by weight of one or more plasticizers;
1 to 40% by weight of one or more low molecular weight skeletons: and 0 to 5% by weight of other components.

[Poly (ethylene oxide) (PEO)]
The said coating composition contains 1 type, or 2 or more types of poly (ethylene oxide) as one of the main components.

  The term “polymer” (eg, referring to poly (ethylene oxide) and non-thermoplastic hydrophilic polymers) refers to organic compounds having repeat units and a weight average molecular weight greater than 10 kDa (10,000 g / mol). Conversely (and complementary), the term “backbone” or “low molecular weight backbone” means that the photoinitiator moiety is covalently bonded and a weight average molecular weight of up to 10 kDa (g / mol) (the photoinitiator The organic compound which has a part) is shown.

  The primary requirement for one or more of the above poly (ethylene oxide) is that the covalently crosslinked coating composition becomes very slippery when swollen with a hydrophilic liquid, such as water or glycerol. Thus, the primary function of the one or more PEOs is to give the swollen coating low friction and high water retention.

The poly (ethylene oxide) (PEO) has a weight average molecular weight (M _w ) greater than 10,000 Da (g / mol). In practice, the PEO can belong to any suitable weight average molecular weight (M _w ), but is preferably 100,000 to 8,000,000 Da (g / mol), most preferably 200,000 to It belongs to the range of 4,000,000 Da (g / mol). A suitable PEO can be purchased from Dow under the trade name Polyox ™.

  It is important to note that the poly (ethylene oxide) does not have any ethylenically unsaturated functional groups such as acrylate moieties, methacrylate moieties or vinyl moieties. On the other hand, the crosslinking of the coating composition and especially the poly (ethylene oxide) is based on other mechanisms.

  In the first major aspect of the present invention, the one or more poly (ethylene oxide) is the only polymer component of the composition. Thus, it should be understood that the poly (ethylene oxide) constitutes 100% by weight of the polymer component.

[Non-thermoplastic hydrophilic polymer]
In a second main aspect of the invention, the polymer component is one or more poly (ethylene oxide) in combination with one or more non-thermoplastic hydrophilic polymers, Alternatively, the two or more poly (ethylene oxides) constitute at least 50% by weight of the total amount of the polymer components.

  Preferably, the one or more poly (ethylene oxide) comprises 50-98%, for example 55-90%, or 60-85% by weight of the total amount of the polymer components, while one or more The non-thermoplastic hydrophilic polymer comprises 2-50%, for example 10-45%, or 15-40% by weight of the remainder, ie the total amount of the polymer components. The thermoplastic nature of the one or more poly (ethylene oxide) provides sufficient flow characteristics of the entire coating composition comprising the non-thermoplastic hydrophilic polymer so that the coating composition is extruded, injected. Very useful for molding and powder coating applications.

  The non-thermoplasticity of the hydrophilic polymer is merely a general requirement, and particularly useful non-thermoplastic hydrophilic polymers are poly (N-vinylpyrrolidone), poly (acrylic acid), polyoxazoline, and copoly (methyl vinyl ether / Is considered to be selected from the group consisting of maleic anhydride).

[A skeleton having a photoinitiator moiety covalently bonded to and / or covalently introduced into the skeleton]
The coating composition is one or more kinds of low molecular weight skeletons as one of the main components, and is covalently bonded to the low molecular weight skeleton and / or covalently bonded to the low molecular weight skeleton. Further included are those having a plurality of photoinitiator moieties introduced.

  The backbone can be selected from a wide range of linear, branched, cyclic and dendritic molecular species, ie, the photoinitiator moiety is “covalently linked” to the backbone. It should be possible to attach more than one (ie at least two) photoinitiator moieties to one or more of the scaffolds by covalent bonds. Furthermore, the backbone can be in the state of two or several backbone fragments held together by a photoinitiator moiety, i.e. the photoinitiator moiety is "shared" in the backbone of the backbone. It is introduced jointly. " It can easily be envisaged that the backbone can have a photoinitiator moiety covalently bonded to the backbone and at the same time have a photoinitiator moiety covalently introduced into the backbone. .

  Examples of skeletons having a photoinitiator moiety covalently bonded to the skeleton are, for example:

  Illustrative examples of skeletons having photoinitiator moieties covalently introduced into their backbone are, for example:

  The scaffold should be capable of having multiple photoinitiator moieties that are covalently bonded to and / or covalently introduced into the scaffold. A “plurality” of photoinitiator moieties means at least two photoinitiator moieties, but in some cases, more than two (eg, 3, 4, 5, 6, or more) photoinitiator moieties.

  In some generally preferred embodiments, the scaffold has at least three photoinitiator moieties that are covalently bonded to and / or covalently introduced into the scaffold.

  With respect to the “filling ratio” of the photoinitiator part, the photoinitiator part comprises one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer, and one or more of the above. It constitutes 0.01 to 20% by weight, for example 0.05 to 15% by weight of the total amount with the low molecular weight skeleton (including the photoinitiator part).

The term “low molecular weight” refers to a backbone (without the photoinitiator moiety) having a weight average molecular weight (M _w ) of up to 10 kDa (10,000 g / mol) therein. Preferably, the weight average molecular weight of the skeleton is 50 to 10,000 Da (g / mol), for example 100 to 10,000 Da (g / mol), in particular 250 to 8,000 Da (g / mol) or 500 to 10 , 1,000 Da (g / mol). In any case, the weight average molecular weight of the “skeleton” refers to the weight of the skeleton not including the photoinitiator part or the total weight of the skeleton fragments not including the photoinitiator part.

  When the skeleton is in the form of two or more skeleton fragments, it is further preferred that each of the fragments has a molecular weight of at least 50 g / mol, for example at least 100 g / mol.

  In order to ensure that the photoinitiator moiety is uniformly distributed within the coating composition, it is covalently bonded to and / or covalently introduced into the low molecular weight backbone within the coating composition. It has proved advantageous to include a photoinitiator moiety that has been modified. By covalently attaching the photoinitiator moiety to the backbone (possibly in the form of two or several backbone fragments), the subsequent movement of the photoinitiator moiety is significantly reduced. Furthermore, for several reasons, it is clear that the photoinitiator moieties that remain unreacted after irradiation do not migrate from the resulting coating.

In one embodiment of the invention, the skeleton has a plurality (eg, at least three) of photoinitiator moieties that are covalently bonded to the skeleton.
In another embodiment of the invention, the scaffold has multiple (eg, at least three) photoinitiator moieties covalently introduced into the scaffold.

  In a third embodiment of interest of the invention, the scaffold is covalently linked to at least one of the scaffolds, and a plurality (eg, at least 3) of covalently introduced into at least one of the scaffolds. One) photoinitiator moiety.

The backbone can be based on a wide range of structures including oligomers and low molecular weight polymers (M _w <10,000), but particularly useful backbones are polyethylene glycol, poly (styrene-co-maleic anhydride), fatty It is generally considered that they are selected from group polyether urethanes, polyether amines (eg Jeffamines from Huntsman), and polyesters.

  One or more of the skeletons can be either hydrophilic or hydrophobic, or both (ie, amphiphilic). Preferably, one or more of the backbones are combined with the one or more polymer components to ensure complete homogeneity and uniform spatial distribution of the combined photoinitiator moieties within the coating composition. Compatible. The ability to achieve a uniform distribution of the photoinitiator portion in the coating composition minimizes the amount of photoinitiator and / or UV irradiation time required to cure.

  Some commercially available scaffolds having a weight average molecular weight of less than 10 kDa are listed below. These frameworks are available from the Sigma-Aldrich Chemical Company unless otherwise specified. Some skeletons are listed in more than one category.

  Nucleophilic skeletons containing hydroxyl groups or amino groups, either as end groups or in the main chain, include: PVOH, poly (diethylene glycol / trimethylolpropane-alt-adipic acid), poly (diethylene glycol / glycerol). -Alt-adipic acid), PEG, [di {poly (ethylene glycol)} adipate], poly (ethylene glycol-ran-propylene glycol), poly (ethylene glycol) -block-poly (propylene glycol) -block-poly ( Ethylene glycol), poly (propylene glycol) -block-poly (ethylene glycol) -block-poly (propylene glycol), poly (propylene glycol), poly (tetrahydrofuran), [polycaprolactone geo ], [Polycaprolactone triol], [poly (diethylene glycol phthalate) diol], poly (4-hydroxystyrene), [polybutadiene, dihydroxyl terminated], [HPEU having hydroxyl end groups], [polyurethanediol solution (proprietary) Aldrich products)], sugar, dextran, pullulan, chitosan oligosaccharide lactate, gelatin (Fibrogen), hydroxypropyl methylcellulose, [poly (tetrahydrofuran), bis (3-amino-1-propyl) -terminated], [poly (ethylene Imine), ethylenediamine endcapping], [poly (propylene glycol) -block-poly (ethylene glycol), bis (3-amino-1-propyl) terminated], [poly (propylene glycol) block-poly (ethylene glycol) -block-poly (propylene glycol), bis (2-amino-1-propyl) -terminated], and [poly (propylene glycol), bis (2-amino-1-propyl) -terminated ]. In particular, dendritic polyols such as Boltorn H20, Boltorn H30 and Boltorn H40 (Perstopp), and Starburst, Priostar DNT-2210 and Priostar DNT-2211 (Dendrific Nanotechnologies) are very good structures for the present invention. . Dendritic polyamines, such as the Starburst series, Priostar DNT-2200 and Priostar DNT-2201 (Dendric Nanotechnologies) also constitute good scaffolds for the present invention. Hyperbranched polynucleophilic reagents can also be used.

  Electrophilic skeletons containing carboxylic acid, anhydride or isocyanate groups, either as end groups or in the main chain, include: poly (acrylic acid), [poly (acrylic acid) sodium salt], [Poly (methacrylic acid) sodium salt], [Poly (styrenesulfonic acid) sodium salt], poly (acrylic acid-co-maleic acid), [poly (acrylonitrile-co-butadiene-co-acrylic acid), dicarboxy terminal ], Polystyrene-block-poly (acrylic acid), gelatin (Fibrogen), [poly (ethylene glycol), di (carboxymethyl) terminated], [poly (acrylonitrile-co-butadiene), dicarboxy terminated], [Polybutadiene, dicarboxy-terminated], poly (isobutylene-alt-maleic anhydride) Acid), [poly (ethylene adipate), tolylene 2,4-diisocyanate terminated, and [poly (propylene glycol), tolylene 2,4-diisocyanate terminated. Dendritic polycarboxylic acids such as the Starburst series, Priostar DNT-2220 and Priostar DNT-2221 (Dendric Nanotechnologies) also constitute good scaffolds for the present invention. Hyperbranched polyelectrophiles can also be used.

  Suitable scaffolds for transesterification and transamination include the following: poly (methyl methacrylate), poly (ethyl methacrylate), poly (butyl methacrylate) and poly (tert-butyl methacrylate).

  Acylatable and electron-rich aromatic backbones include the following: polystyrene-block-poly (acrylic acid), poly (2-vinylpyridine), poly (2-vinylcarbazole) , Polycarbonate, poly (α-methylstyrene), polystyrene, poly (2-vinylnaphthalene) and polyacenaphthylene.

  Skeletons containing graftable ether linkages include: PEG, HPEU, [di {poly (ethylene glycol)} adipate], poly (ethylene glycol-ran-propylene glycol), poly (ethylene glycol)- block-poly (propylene glycol) -block-poly (ethylene glycol), poly (propylene glycol) -block-poly (ethylene glycol) -block-poly (propylene glycol), poly (propylene glycol), poly (tetrahydrofuran), and [Poly (diethylene glycol phthalate) diol].

  Additional nucleophilic skeletons having a weight average molecular weight of less than 10 kDa can be formed by radical homopolymerization of at least one monomer, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate and 4-hydroxystyrene. When a copolymer is produced, the copolymer can also include one or more of the following monomers having relatively inert side chains: styrene, α-methylstyrene, ring-alkylation. Styrene such as vinyl toluene, vinyl pyridine, vinyl imidazole, (meth) acrylic acid esters such as methyl methacrylate, (meth) acrylamide, such as acrylamide, vinylamine amides such as N-vinylformamide, vinyl nitrile such as Acrylonitrile, vinyl esters such as vinyl acetate, ethylene, propylene, 1-butene, isobutylene, butadiene, isoprene, chloroprene, and vinyl halides such as vinyl chloride.

  Further electrophilic skeletons containing carboxylic acid, sulfonic acid or phosphonic acid and having a weight average molecular weight of less than 10 kDa are at least one monomer, (meth) acrylic acid, maleic acid, fumaric acid, crotonic acid, tiglic acid, Itaconic acid, S-vinylsulfonic acid, vinylbenzenesulfonic acid, 2-acrylamido-2-methylpropanesulfonic acid (AMPS), 2-sulfoethyl methacrylate, N, N-dimethyl-N-methacryloyloxyethyl-N- (3 It can be formed by radical homopolymerization, random copolymerization or block copolymerization of -sulfopropyl) ammonium betaine (SPE) and P-vinylphosphonic acid. When a copolymer is produced, it can also include one or more monomers having relatively inert side chains, referred to under the “additional nucleophilic backbone” described above.

  Further backbones suitable for transesterification and transamination and having a weight average molecular weight of less than 10 kDa are alkyl (meth) acrylates, alkyl crotonates, alkyl tiglates, dialkyl maleate salts, dialkyl fumarate, and dialkyl It can be formed by radical homopolymerization, random copolymerization or block copolymerization of at least one monomer belonging to the itaconate group. When a copolymer is produced, the copolymer can also contain one or more of the following monomers whose side chains should not affect transesterification or transamination: styrene, α-methylstyrene , Ring-alkylated styrenes such as vinyl toluene, vinyl pyridine, vinyl imidazole, (meth) acrylic acid esters such as methyl methacrylate, (meth) acrylamides such as acrylamide, vinylamine amides such as N-vinylformamide, Vinyl nitriles such as acrylonitrile, ethylene, propylene, 1-butene, isobutylene, butadiene, isoprene, chloroprene, and vinyl halides such as vinyl chloride.

  Additional backbones comprising an acylatable, electron-rich aromatic system having a weight average molecular weight of less than 10 kDa are at least one styrene monomer, such as styrene, α-methylstyrene, ring-alkylated styrene, or 4 -It can be formed by radical homopolymerization, random copolymerization or block copolymerization of hydroxystyrene. When a copolymer is produced, the copolymer can also include one or more of the following monomers having non-acylatable side chains: (meth) acrylic acid esters such as methyl methacrylate, (meta ) Acrylamide, such as acrylamide, vinylamine amide, such as N-vinylformamide, vinyl nitrile, such as acrylonitrile, vinyl ester, such as vinyl acetate, ethylene, propylene, 1-butene, isobutylene, butadiene, isoprene, chloroprene, and Vinyl halides such as vinyl chloride.

  Additional backbones containing graftable ether linkages having a weight average molecular weight of less than 10 kDa are at least one monomer, PEG methacrylate, PEG methyl ether methacrylate, PEG ethyl ether methacrylate, PEG methyl ether acrylate, PEG phenyl ether acrylate, poly ( It may be formed by radical homopolymerization, random copolymerization or block copolymerization of propylene glycol) methacrylate, poly (propylene glycol) acrylate, and poly (propylene glycol) methyl ether acrylate. When a copolymer is produced, the copolymer may also be one or more non-grafting monomers, styrene, α-methyl styrene, ring-alkylated styrene such as vinyl toluene, vinyl pyridine, vinyl imidazole, (meta ) Acrylamide, such as acrylamide, amides of vinylamine, such as N-vinylformamide, vinyl nitrile, such as acrylonitrile, ethylene, propylene, 1-butene, isobutylene, butadiene, isoprene, chloroprene, and vinyl halides, such as vinyl chloride , (Meth) acrylic acid, maleic acid, fumaric acid, crotonic acid, tiglic acid, itaconic acid, S-vinylsulfonic acid, vinylbenzenesulfonic acid, 2-acrylamido-2-methylpropanesulfonic acid (AMPS) 2-sulfoethyl methacrylate, N, N-dimethyl -N- methacryloyloxyethyl -N- (3- sulfopropyl) ammonium betaine (SPE), and may include a P- vinylphosphonic acid.

[Photoinitiator]
The main function of the photoinitiator part is to ensure good crosslinking of the thermoplastic and hydrophilic coating to itself and the substrate in order to obtain good cohesion and adhesion to the substrate. It is to be. Preferred properties of one or more of the photoinitiators include: (i) good overlap between lamp emission spectrum and photoinitiator absorption spectrum; (ii) the photoinitiator absorption spectrum and the coating. Less overlap with the intrinsic mixed absorption spectrum of other components (ie poly (ethylene oxide)); and of the photoinitiator moiety comprising the backbone to which the moiety is covalently bonded, The compatibility with one or more poly (ethylene oxides) of the coating is good.

  The photoinitiator effectively converts light from a UV or visible light source into reactive radicals that can draw hydrogen atoms and other labile atoms from the polymer, and thus can perform covalent crosslinking. Should. If desired, amines, thiols and other electron donors can be added. Radical photoinitiators are special cases where the cleavage type (Norish type I reaction) or the non-cleavage type (Norish type II reaction) are, for example, A. Gilbert, J. Baggott “Essentials of Molecular Photochemistry”, Blackwell. , London, 1991). Upon excitation, the cleavage photoinitiator splits spontaneously into two radicals, at least one of which is sufficiently reactive to abstract hydrogen atoms from most substrates. Benzoin ethers (including benzyl dialkyl ketals), phenyl hydroxyalkyl ketones and phenylaminoalkyl ketones are important examples of cleavage type photoinitiators. Although the addition of an electron donor is not required, the overall efficiency of the cleaved photoinitiator can be increased according to a mechanism similar to that described for the non-cleavable photoinitiator below.

  Recently, a new class of β-ketoester photoinitiators has been published by Ashland Specialty Chemical, USA (2005) from L Gould, S.M. Narayan-Sarathy, T .; E. Hammond and R.A. B. Introduced by Fechter: RadTech Europe 05, Barcelona, Spain, October 18-20 2005, vol. 1, p. 245-51, “Novel Self-Initiating UV-Cable Resins: Generation Three”, from Vincentz. After base-catalyzed Michael addition of an ester to a polyfunctional acrylate, a network with multiple quaternary carbon atoms is formed, each having two adjacent carbonyl groups. Upon UV or visible light excitation, these photoinitiators can be cleaved primarily by the Norrish Type I mechanism and further cross-linked without any common photoinitiators present and cure thick layers. it can. Such self-initiating systems are within the scope of the present invention.

  Excited non-cleavable photoinitiators do not split into radicals, but abstract hydrogen from organic molecules or more effectively extract electrons from an electron donor (eg, amine or thiol). Electron transfer produces a radical anion on the photoinitiator and a radical cation on the electron donor. This is followed by proton transfer from the radical cation to the radical anion to produce two uncharged radicals; these radicals on the electron donor are sufficient to draw hydrogen atoms from most substrates. Has reactivity. Benzophenone, thioxanthone, xanthone, anthraquinone, fluorenone, dibenzosuberone, benzyl and phenyl ketocoumarin are important examples of non-cleavable photoinitiators. Most amines having a C—H bond in the α-position to the nitrogen atom and many thiols act as electron donors.

Another self-initiating system based on maleimide is also from Albemarle Corporation and Brady Associates LLC, both from USA (2003), CK. Nguyen, W .; Kuang and CA. Specified by Brady: RadTech Europe 03, Berlin, Germany, November 3-5, 2003, vol. 1, p. 589-94, “Maleimide Reactive Oligomers” following Vincentz. Maleimide initiates radical polymerization mainly by acting as a non-cleavable photoinitiator and simultaneously polymerizes spontaneously by radical addition at both ends of the maleimide double bond. Furthermore, the strong UV absorption of maleimide disappears in the polymer, ie maleimide is a photobleaching photoinitiator; this makes it possible to cure thick layers.
Such maleimide-containing systems are within the scope of the present invention.

  Some photoinitiator blends are described, for example, in J. Org. P. Fouassier: “Excited-State Reactivity in Radical Polymerization Photo-Initiators”, Ch. 1, pp. 1-61, “Radiation curing in Polymer Science and technology”, Vol. II (“Photo-initiating Systems”), J. Org. P. Fouassier and J.M. F. In some cases, Rabek may exhibit synergistic properties as described in Edit, Elsevier, London, 1993. Briefly, in a pair of [4,4′-bis (dimethylamino) benzophenone + benzophenone], [benzophenone + 2,4,6-trimethylbenzophenone], [thioxanthone + methylthiophenylmorpholinoalkylketone], from a photoinitiator Efficient energy transfer or electron transfer takes place to other photoinitiators. However, many other useful combinations can be envisaged.

  Furthermore, Irgacure 2959 and benzophenone covalently bonded within the molecule of 4- (4-benzoylphenoxyethoxy) phenyl 2-hydroxy-2-propylketone have considerably higher initiation efficiencies than a mere mixture of two separate compounds. It has been found in recent years to give. From S. Vienna University of Technology, Australia (2005). Kopeinig and R.K. See Liska: RadTech Europe 05, Barcelona, Spain, October 18-20 2005, vol. 2, p. 375-81, “Further Covalent Bonded Photoinitiators” following Vincentz. This indicates that when different photoinitiators are present in the same oligomer or polymer, the different photoinitiators can exhibit a significant synergistic effect. The covalently bonded photoinitiator can also be applied to the present invention.

  Thus, in one embodiment of interest of the invention, the photoinitiator moiety comprises at least two photoinitiator moieties. It is preferred that the absorbance peaks of different photoinitiators are at different wavelengths and that the total amount of light absorbed by the system increases. The different photoinitiators can be all cleavable, all non-cleavable, or a mixture of cleavable and non-cleavable.

  Preferred cleavage photoinitiators include benzoin ethers (including benzyl dialkyl ketals), such as Irgacure 651 (Ciba); phenylhydroxyalkyl ketones such as Darocur 1173, Irgacure 127, Irgacure 184, and Irgacure 2959 (all Ciba) Esacure KIP 150 and Esacure One (both Lamberti); phenylaminoalkyl ketones such as Irgacure 369 (Ciba), Irgacure 379 (Ciba), and Chivacure 3690 (Double Bond thiomethyl ketone; , Irgacure 907 (Ciba) and Chivacure 3482 (Double bond Chemicals); and mono- or dibenzoylphosphine oxides, such as Irgacure 819 and Darocur TPO (both Ciba).

  Preferred non-cleavable photoinitiators are benzophenone, 4-benzoylbenzoic acid (= 4-carboxybenzophenone) and its esters, 2-benzoylbenzoic acid (= 2-carboxybenzophenone) and its esters, 4,4′-bis ( Dimethylamino) benzophenone (Michler ketone), 2,4,6-trimethyl-benzophenone, BTDA, Omnipol BP (IGM resin), and other benzophenone derivatives; thioxanthones such as Omnipol TX (IGM resin) and 2-carboxymethoxythioxanthone ( Pentagon Fine Chemical); xanthone; anthraquinone; fluorenone; dibenzosuberone; benzyl and other α-diketo compounds such as camphorquinone; and phenyl ketocoumarin is there. Preferred optional electron donors are benzocaine (ethyl 4-aminobenzoate), PVP-DMAEMA, tribenzylamine, triethanolamine, 2- (N, N-dimethylamino) ethanol, and N, N-dimethylethylenediamine. .

  In general, the most preferred photoinitiator is selected from the group of Irgacure 2959, BTDA and its derivatives, 4-carboxybenzophenone and its derivatives, 2-carboxybenzophenone and its derivatives, and 2-carboxymethoxythioxanthone and its derivatives. Is.

[Improved photoinitiator suitable for covalent bonding to the skeleton]
Most common photoinitiators such as benzoin ethers (eg, Irgacure 651, cleaved), hydroxyalkyl phenyl ketones (eg, Darocur 1173, cleaved), benzophenones (eg, benzophenone, non-cleavable), and thioxanthone ( For example, 2-isopropylthioxanthone (non-cleavable) does not have a functional group and cannot be easily bonded to the skeleton. For this reason, photoinitiators having one or more functional groups are preferred. The number of commercially available photoinitiators with functional groups is limited. This is probably because, conventionally, monofunctional, unpolymerized components have been used in coating compositions. Thus, it may be necessary to custom synthesize certain functional photoinitiators so that photoinitiators can be attached to the backbone.

On the other hand, a vast number of chemical reactions that form a covalent bond between two separate compounds are known and the present invention relates to primary hydroxyl groups or amino groups (ie strong nucleophilicity) on the photoinitiator. ), Or reactive carboxylic acid derivatives such as anhydrides or acid chlorides (ie strong electrophilicity).
The following example illustrates this specifically.

  Irgacure 2959 (Ciba) is a nourish type I photoinitiator containing a nucleophilic primary hydroxyl group.

  If higher nucleophilicity is required, Irgacure 2959 can be sulfonated and then converted to the corresponding primary amine. For example, see Gabriel synthesis (see, for example, J. March: “Advanced Organic Chemistry. Reaction, Mechanisms, and Structure”, 3. ed., P. 377-9, Wiley-Interscience, New York, 1985).

  The hydroxyl group in Irgacure 2959 can be functionalized in several ways to electrophilic acid derivatives so that the Irgacure 2959 can react with free hydroxyl and amino groups.

1. Acid derived from Cr (VI) -oxidation of Irgacure 2959:

2. Acid derived from a 1: 1 reaction of Irgacure 2959 and succinic anhydride:

3. Acid derived from a 1: 1 reaction of Irgacure 2959 and maleic anhydride:

These acids can be conveniently converted to the corresponding reactive acid chlorides by treatment with SOCl ₂ . Care must be taken when using the acid chloride immediately after formation to avoid reaction between the acid chloride moiety and the tertiary hydroxyl group in the hydroxyalkyl portion of the ketone.

On the other hand, the corresponding 2-hydroxyethyl benzoyl benzoate, for example, electrophilic 2-, 3- or 4-benzoyl benzoyl chloride (SOCl ₂ and with the addition of a large excess of ethylene glycol to form: , Which is a derivative of the non-cleavable photoinitiator benzophenone, produced by reaction with commercially available 2-, 3- or 4-benzoylbenzoic acid, can be converted to a nucleophilic reagent.

  When ethanolamine or ethylenediamine is used instead of ethylene glycol, the corresponding N- (2-hydroxyethyl) benzoylbenzamide and N- (2-aminoethyl) benzoylbenzamide can be formed. All these nucleophilic derivatives can be reacted with, for example, polyanhydrides such as poly (styrene-co-maleic anhydride) (SMA) (see below) and isocyanates. Alternatively, 2-, 3- or 4-hydroxybenzophenone, or 2-, 3- or 4-aminobenzophenone can be purchased and used directly, but the nucleophilicity of these hydroxyl and amino groups is as described above. Will be considerably less than the nucleophilicity of the ethylene glycol, ethanolamine and ethylenediamine derivatives.

  Thioxanthone is also a very interesting non-cleavable photoinitiator. This is because they absorb around 400 nm and can be cured by UV-A light or visible blue light. An example of a derivative of thioxanthone is 2-carboxymethoxyxanthone, which can be converted to an electrophilic acid chloride and, if necessary, an excess of ethylene glycol (2-hydroxyethylthioxanthone- 2-yloxyacetate), ethanolamine (produces N- (2-hydroxyethyl) thioxanthone-2-yloxyacetamide), or ethylenediamine (N- (2-aminoethyl) thioxanthone-2-yloxy) Can be converted to nucleophilic species by reaction with (forms acetamide).

[Example of photoinitiator moiety and skeleton bond]
A nucleophilic skeleton, such as Boltorn H20 having 16 free OH groups, can be reacted directly with an electrophilic photoinitiator, such as 4-benzoylbenzoyl chloride, to produce a photoactive polyester.

  When acid chloride is added to the Boltorn solution, the degree of photoinitiator substitution on the polyol can be controlled.

The acidic component of the electrophilic skeleton, for example, a carboxylic acid group in poly (acrylic acid) is converted to the corresponding acid chloride, sulfonyl chloride or phosphonyl chloride by treating with SOCl ₂ or PCl _5. Can do. Alternatively, the acid can be treated with a dehydrating agent such as N, N′-dicyclohexylcarbodiimide to produce a species similar to an acid anhydride with respect to reactivity towards nucleophilic reagents. The acid chlorides, sulfonyl chlorides and phosphonyl chlorides and corresponding anhydrides are activated in a direction to react with a nucleophilic photoinitiator, such as Irgacure 2959, and the respective ester, amide, sulfonyl ester, sulfonamide, phospho Nyl esters and phosphonamides are formed.

Photoactive esters and amides can be formed from the skeleton by transesterification or transamination of the ester with an excess of photoactive nucleophilic reagent. If a catalyst (eg manganese or zinc salt) can be added and the photoinert component to be removed has a lower boiling point than the photoactive component, the photoinert component is removed from the equilibrium state. As such, reduced pressure can be applied.
The two reactions can be expressed as follows:
Backbone -CO-OR + HO-photoinitiator → Backbone -CO-O-photoinitiator + HO-R (transesterification)
Skeletal -CO-OR + H ₂ N- photoinitiator → skeleton -CO-NH- photoinitiator + HO-R (transamination)

The “backbone—CO—OR” can be, for example, poly (diethyl maleate) having a weight average molecular weight of 10 kDa or less. “HO-photoinitiator” includes, for example, Irgacure 2959, 2- or 4-hydroxybenzophenone, 2-hydroxyethyl 4-benzoylbenzamide, N- (2-hydroxyethyl) -2-benzoylbenzamide, 2-hydroxyethylthioxanthone It can be 2-yloxyacetate or N- (2-hydroxyethyl) thioxanthone-2-yloxyacetamide. “H ₂ N-photoinitiator” is, for example, Irgacure 2959 amine, N- (2-aminoethyl) -4-benzoylbenzamide, or N- (2-aminoethyl) thioxanthone-2-yloxyacetamide Can do.

  Ethers such as PEG or poly (propylene glycol) can be acyloxylated by reacting with a tert-butyl peroxy ester of a carboxyl-containing photoinitiator to give the ether ester and tert-butyl alcohol (J. March: “See Advanced Organic Chemistry. Reaction, Mechanisms, and Structure, 3. ed., P. 636-7, Wiley-Interscience, New York, 1985. As an example, a benzophenone derivative (2-benzoylbenzoyl cloroyl). The bond is shown here.

  The above reaction can also be carried out using an acid chloride derivative of BTDA or a Norrish type I photoinitiator, such as Irgacure 2959 acid chloride.

  Ethers such as PEG or poly (propylene glycol) can be alkylated (ie, added) to the photoinitiator double bond in the presence of peroxide to give the corresponding alkylated ether. Best results are obtained from electron deficient alkenes such as maleic anhydride (C. Walling, ES Huyser (1963): “Free radical additions to forms carbon-bonds”, Organic Reactions 49, 13). For example). Nucleophilic photoinitiators (eg, Irgacure 2959) can acquire electron deficient double bonds by esterification with maleic anhydride.

  As the skeleton, an isocyanate-capped, low molecular HPEU can also be functionalized with a nucleophilic photoinitiator (eg, Irgacure 2959) at both ends to produce a photoactive polyurethane.

  Similarly, the side chain of the backbone poly (styrene-co-maleic anhydride) (SMA) can be modified with a nucleophilic photoinitiator (eg, Irgacure 2959 or modified benzophenone).

[Example of skeletal conversion to photoinitiator]
Benzophenone can be produced by in situ Friedel-Crafts benzoylation of an electron-rich aromatic moiety using benzoyl chloride and a Lewis acid as a catalyst (eg, AlCl ₃ ). Aromatic anhydrides such as phthalic anhydride, pyromellitic dianhydride (1,2,4,5-benzenetetracarboxylic dianhydride) and BTDA are less reactive than benzoyl chloride, Can be used. When the aromatic moiety is vacant, the para compound is a major product due to the size of the benzoyl group (eg, J. March: “Advanced Organic Chemistry. Reaction, Mechanisms”). , And Structure ", 3. ed., P. 484-7, Wiley-Interscience, New York, 1985). However, the above method can also be used with aromatic moieties that are not vacant in the para position.

The aromatic moiety may be a homopolymer of vinyl pyridine, styrene, α-methyl styrene, vinyl toluene, alkoxy styrene, aryloxy styrene, ethyl styrene, tert-butyl styrene, isopropyl styrene, dimethyl styrene, and other alkylated styrenes or It can be part of a copolymer. Any aromatic diisocyanate or aromatic diol used in the production of HPEU can also be benzoylated. The aromatic ring of benzoyl chloride can also itself be substituted; the electron donating group on benzoyl chloride increases the reaction rate.
As an example, the following reaction occurs using ordinary polystyrene.

  Correspondingly, α, α-dialkyl-α-hydroxy substituted acetophenones (ie, cleaved photoinitiators) are also electron-rich using related α, α-dialkyl-α-hydroxyacetyl chlorides. It can be formed in situ by Friedel-Crafts acylation of the aromatic moiety. For example, to produce 2-hydroxy-2-propyl phenyl ketone, the electron-rich aromatic moiety can be converted to 2-hydroxy-2-methylpropionyl chloride (= 2-hydroxyisobutyryl chloride = α-hydroxyisobutyrate). Treatment with ril chloride). The acid chloride precursor, α-hydroxyisobutyric acid, can be purchased from Sigma-Aldrich.

  It should be noted that once the acid chloride is formed, it does not react with tertiary hydroxyl groups to form polyester poly (2-isobutyrate).

[Example of the synthesis of a skeleton having a photoinitiator introduced into the main chain]
Bifunctional electrophilic photoinitiators, such as BTDA, react with dihydroxy- or diamino-terminated, nucleophilic backbone fragments such as small molecule HPEU to produce the corresponding photoinitiator-containing backbones described below. can do.

  The resulting skeleton has a photoinitiating moiety in the main chain instead of a side chain. The skeleton is within the scope of the present invention. The reaction is best carried out in polar organic solvents such as DMSO, DMA, DMF, NMP and pyridine.

  The crosslinking reaction of the photoactive BTDA poly (ester urethane acid) is as follows.

  Jeffamine D-230 (Huntsman; hydrophobicity; a = 2 to 3, b = c = 0) shown below also reacts positively with BTDA.

  As mentioned above, BTDA can also react with the hydroxyl end groups of low molecular weight backbone fragments, such as low molecular weight PEG and other low molecular weight polyethers. Upon photocuring with the BTDA-containing backbone of PEO, a stable, cross-linked, hydrophilic polymer network forms and becomes very slippery when wet.

Detailed procedure for the preparation of medical device elements
[Step (i)]
In an initial step of the method, the pre-fabricated shaped article and / or the thermoplastic base polymer is prepared.

  As is apparent from the section “Thermoplastic Base Polymer”, the base polymer is a commercial product that is traded in a suitable physical form, for example, a suitable physical form such as pellets, chips, granules, etc. There is typically. Thus, usually no pretreatment or preparation is necessary.

  If a mixture of two or more base polymers is used, the polymer is in molten form or dissolved in a common solvent and then general procedures and general equipment such as It is generally desirable to homogenize the polymer either by removing the solvent by spray coating, roller drying or precipitation in a non-solvent. Preferably, the solvent solution is cast into a film and the solvent is removed from the film by any common technique. The solvent can be removed using reduced pressure and / or elevated temperature. The resulting uniform blend can be chipped or pelletized prior to melt processing.

  From the “Prefabricated shaped article” section, the shaped article is often available from commercial sources or can be easily prepared within the prior art as known to those skilled in the art. It is even clearer. As a very interesting alternative, in certain embodiments on the same process line to which the method is applied, the shaped article can be prepared immediately prior to use of the method of the present invention. Furthermore, the prefabricated shaped article can be pretreated and further precoated before use in the method of the present invention.

[Step (ii)]
The coating composition in the preparation of the medical device element can be prepared by dissolving the components in a common solvent. The solvent is then removed and one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and one or more skeletons with photoinitiator moieties, and any additives prepared for extrusion. A uniform blend can be left. Any general procedure or equipment can be used for solvent removal, such as spray coating, roller drying or precipitation in non-solvents such as acetone or carbon tetrachloride. Preferably, the solvent solution is cast onto a film and the solvent is removed from the film by any common technique. The cast film can then be heated in a convection oven at a temperature from ambient to about 70 ° C. Reduced pressure can be used to assist in the removal of the solvent. The resulting uniform blend can be chipped or pelletized prior to melt processing or powder coating.

  Subsequently, the pelletized coating composition is extruded or injection molded onto the pre-fabricated shaped article or the thermoplastic substrate polymer as described with respect to step (iii) below. Or powder coating.

[Step (iii)]
This step comprises the step of (ii) coating composition on the prefabricated shaped article together with the thermoplastic substrate polymer of step (i) or the layer of coating composition above. The prefabricated shaped article and substrate comprising extruding, injection molding, or powder coating to provide a prefabricated shaped medical device element and / or base polymer. When both material polymers are present, the pre-fabricated shaped article has a layer of the base polymer thereon.

Three main embodiments are included in this step.
In the first main embodiment, only a prefabricated shaped article is prepared in step (i), and step (iii) is performed on the prefabricated shaped article of step (i) Extruding, injection molding or powdering the coating composition of step (ii) to provide the pre-fabricated shaped medical device element having a layer of the coating composition thereon Including coating.

  In the second main embodiment, only the thermoplastic base polymer is prepared in step (i), and step (iii), together with the thermoplastic base polymer of step (i), is the coating composition of step (ii) Including extruding or injection molding the article to provide a medical device element of the thermoplastic substrate polymer having a layer of the coating composition thereon.

  In a third main embodiment, in step (i), a prefabricated shaped article as well as a thermoplastic base polymer is provided, wherein step (iii) is combined with the thermoplastic base polymer of step (i) Extruding the coating composition of step (ii) on the prefabricated shaped article to provide the prefabricated shaped article medical device element and the thermoplastic substrate polymer, or The pre-fabricated shaped article comprising injection molding has a layer of the thermoplastic base polymer thereon, and the thermoplastic base polymer has a layer of the coating composition thereon Have

A third major embodiment is discussed below.
In a first variant of the first main embodiment, a melt of the coating composition is extruded onto the surface of a prefabricated shaped article (see eg Example 6).

In a second variant of the first main embodiment, the melt of the coating composition is injection molded onto the surface of a prefabricated shaped article.
In a third variant of the first main embodiment, the coating composition is powder coated onto the surface of a prefabricated shaped article.

  In one variation of the second main embodiment, the thermoplastic substrate polymer melt and the coating composition melt are extruded and have a coating of the coating composition on the surface of the substrate polymer. Get a shaped product.

  In another variation of the second main embodiment, the thermoplastic substrate polymer melt and the coating composition melt are injection molded to provide a coating of the coating composition on the surface of the substrate polymer. Obtain a shaped product. This interesting variation can be achieved in a two-step injection molding process in which the outer layer of the coating composition is first molded and then the thermoplastic substrate polymer is molded.

  In one variant of the third main embodiment, the base polymer melt and the coating composition melt are extruded onto the surface of a prefabricated shaped article.

  In a variant of the third main embodiment, the melt of the base polymer and the melt of the coating composition are injection molded onto the surface of a prefabricated shaped article. This interesting variation can be achieved in a two-step injection molding process in which the outer layer of the coating composition is first molded with a solid core and then pre-formed as a core. The thermoplastic base polymer is molded using the produced shaped article.

  The coating composition can be extruded / coextruded with the base polymer using any common and commercially available extrusion equipment. Suitable coextrusion equipment is described, for example, in Genca Cable Company, Clearwater, Fla. Or Wayne Machine and Die Company, Totowa, NJ. Or a custom co-extrusion device can be designed for the production of specific medical device elements, if desired.

Alternatively, the composition can be crosshead extruded or coextruded onto a prefabricated shaped product, such as a polymer product. Extrusion of the skin layer is a common process in which a melt of a thermoplastic material (here, the thermoplastic base polymer or the coating composition) is formed into a solid, continuous, form. It is fed to the surface while measuring directly through a die.
In addition, (co) extrusion and injection molding can be performed as described in US Pat. Nos. 5,061,424 and 6,447,835.

  The coating composition can be injection molded to provide a coating on a thermoplastic base polymer or prefabricated shaped article. The injection molding variation can be one or two process steps. In one of the variants corresponding to the second variant of the first main embodiment (see above), the coating composition is applied to the final product using the pre-fabricated solid core of the shaped product. Inject into a mold with the opposite shape at high pressure. In a second variant corresponding to the second variant of the second main embodiment (see above), step (iii) is carried out using two sub-steps, i.e. a solid core, with the coating composition. Can be achieved by first shaping and taking out the solid core and then molding the thermoplastic substrate polymer with a slightly smaller solid core if desired.

  In a third variant, which corresponds to the second variant of the third main embodiment (see above), step (iii) is carried out using two sub-steps, i.e. a solid core. Can be achieved by first molding and taking out the solid core, followed by molding the thermoplastic base polymer using a solid product previously made as a solid core. In a fourth variant, which corresponds to the second variant of the second main embodiment (see above), step (iii) is carried out using two sub-steps, i.e. a certain size cavity. This can be accomplished by first shaping the thermoplastic base polymer and then molding the coating composition on the thermoplastic base polymer using a slightly larger cavity.

  In a fifth variant, which corresponds to the second variant of the third main embodiment (see above), step (iii) is carried out as two sub-steps: a size cavity and a core Using the prefabricated shaped article, the thermoplastic base polymer is first molded, the cavity is taken out, and then a slightly larger cavity is used on the thermoplastic base polymer. This can be achieved by molding the coating composition. For powder coatings generally following general principles, a pelletized compound comprising one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and one or more backbones with photoinitiator moieties. Can be pulverized to a particle size in the range of 5 to 250 μm. Usually, a powder coating composition having a particle size distribution in the range of 10 to 100 μm is preferred.

  The powder coating composition is typically applied by spraying or by using a fluidized bed system. In the case of a metal substrate (a shaped article prepared in advance), it is preferable to apply the coating by electrostatic spraying. In the case of a spray, the powder coating can be applied in a single scan or multiple passes to provide a film with a preferred thickness.

  After applying the powder by spraying or by using a fluidized bed system or by powder coating application techniques known in the art, thermoplastic powders may be about 80-200, depending on the type of substrate. Heating to 0 ° C. forms a uniform coating layer having a thickness of about 5 to 250 μm, usually about 10 to 100 μm.

The dry layer thickness of the coating composition is generally 2.5 to 500 μm, preferably 2.5 to 125 μm.
The thickness of the substrate polymer (if present) is typically 5 to 1000 μm, more typically 10 to 50 μm or 100 to 500 μm.

  The medical device element obtained by the above method is dried and generally non-tacky until wetted by finger touch or by wetting with a liquid and is humidified by finger touch or by wetting with a liquid. The medical device element then becomes slippery and has a smooth surface.

  The method of the present invention is particularly useful for the preparation of medical device elements having the shape of rods or tubes. For example, a catheter so prepared becomes smooth immediately upon contact with a water-containing fluid, thereby significantly contributing to the comfort of the patient undergoing catheterization. Extruded rods in the form of guide-wires become smooth when wet and thus can slide easily.

After extrusion or injection molding, the medical device element may need to be cooled, for example, by cold air or in a water bath.
Given this, the presently most preferred embodiment of step (iii) involves (co) extrusion.

[Step (iv)]
In the next step, the coating composition is irradiated with UV or visible light so that the coating composition is covalently crosslinked. UV or visible light is defined as having a wavelength of 100-750 nm. Particularly relevant wavelength ranges are 100-250 nm and 250-400 nm (both UV), and 400-750 nm (visible light). In the context of the present invention, the terms “photocuring”, “photocuring” and the like refer to curing using UV or visible light. Curing using ultraviolet light is preferred, but curing using blue light (visible light wavelength range) can equally be applied.

  UV or visible light can be applied using a polychromatic or monochromatic UV or visible light source, has an emission spectrum that matches the absorbance of one or more of the photoinitiators and has high intensity Those are preferred. In the absence of reactive monomers, the coating is crosslinked by only a combination of two molecules of radicals derived from photoinitiators irradiated with UV (or visible light). Thus, when the light intensity is doubled, the radical concentration is doubled, but the amount of crosslinking reaction is quadrupled. This is why a high light intensity is preferred. Suitable pleochroic light sources include: (i) a deuterium lamp, (ii) a mercury lamp doped with iron, gallium or other elements that may predominately affect the output spectrum, (iii) Xenon arc lamps (both pulsed and unpulsed), and (iv) halogen lamps (giving mainly visible light). Suitable monochromatic light sources include: (v) gas and solid state lasers (in some cases, frequency doubled, tripled, quadrupled or other frequency manipulation means) (both pulsed and unpulsed) ), And (vi) light emitting diodes in the UV and visible regions (both pulsed and unpulsed).

The optimum irradiation time and light intensity can be easily found by routine experimentation by those skilled in the art. For empirical reasons (eg large scale production of medical devices), the irradiation time should preferably be 300 seconds or less, and in particular 600 seconds or less.
Presently most preferred embodiments of the present invention include:

I. A method for preparing a medical device element comprising the following steps;
(I) providing a thermoplastic substrate polymer;
(Ii) providing a coating composition;
(Iii) Coextrusion of the coating composition of step (ii) and the thermoplastic substrate polymer of step (i) to provide a medical device element of the substrate polymer having a layer of the coating composition thereon. Steps to do:
(Iv) irradiating the coating composition with UV or visible light such that the coating composition is covalently crosslinked.

II. A method for preparing a medical device element comprising the following steps;
(I) providing a prefabricated shaped article and an optional thermoplastic substrate polymer;
(Ii) providing a coating composition;
(Iii) a prefabricated shaped medical device element to provide a prefabricated medical device element and, if present, a substrate polymer having a layer of the coating composition thereon. And, if present, co-extruding the coating composition of step (ii) over the thermoplastic substrate polymer of step (i), where the substrate polymer is present, The prefabricated shaped article has the above described polymer layer on the prefabricated shaped article:
(Iv) irradiating the coating composition with UV or visible light such that the coating composition is covalently crosslinked.

III. A method for preparing a medical device element comprising the following steps;
(I) providing a thermoplastic substrate polymer;
(Ii) providing a coating composition;
(Iii) injection molding the coating composition of step (ii) and the thermoplastic base polymer of step (i) to provide a medical device element of the base polymer having thereon a layer of the coating composition. Steps to do:
(Iv) irradiating the coating composition with UV or visible light such that the coating composition is covalently crosslinked.

IV. A method for preparing a medical device element comprising the following steps;
(I) providing a prefabricated shaped article and an optional thermoplastic substrate polymer;
(Ii) providing a coating composition;
(Iii) the pre-fabricated medical device element and, if present, the pre-fabricated to provide the base polymer having a layer of the coating composition thereon Injection molding the coating composition of step (ii) onto the shaped article and, if present, the thermoplastic base polymer of step (i), where the base polymer is present The prefabricated shaped article has the base polymer layer on the prefabricated shaped article:
(Iv) irradiating the coating composition with UV or visible light such that the coating composition is covalently crosslinked.

[New medical device]
The medical device element produced by the method described above is considered to represent a new product per se. The medical device is characterized by a residue of the photoinitiator moiety, and the residue is the one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer, and the one or more It constitutes 0.01 to 20% by weight of the total amount with two or more low molecular weight skeletons.

  As used herein, the term “residue of photoinitiator moiety” means that the photoinitiator moiety performs a desired function (ie, crosslinking of the coating composition, in particular one or more of the poly (ethylene oxide) and It refers to the form of the photoinitiator moiety present after the chain crosslinking of any non-thermoplastic hydrophilic polymer (either directly or indirectly). The residues of the photoinitiator moiety are typically recognized as being transferred or cleaved according to the molecular level compared to the original photoinitiator.

The residue content of the photoinitiator moiety in the coating could be measured by NMR (solution or solid state) spectroscopy. This is because the photoinitiator resonates in the spectrum of the aromatic moiety, while PEO has resonance in the aliphatic moiety. For example, the integrated intensity obtained from the ¹ H-NMR spectrum can be used to measure the content of the photoinitiator compared to other types in the coating. Alternatively, from elemental analysis and / or XPS analysis, the semi-chemical formula of the coating can be derived and used directly to determine the content of photoinitiator in the coating. Another method is to use the intensity of clearly distinguishable bands in the UV-vis, IR and / or NIR spectra of both the photoinitiator and other species and entities in the coating. By comparing the relative intensities, the content of the photoinitiator can be determined. Chromatographic techniques, e.g., HPLC, SEC and LC-MS ⁿ may also be by comparing the integrated intensity of the chromatogram used to determine the content of the photoinitiator present in the coating. In LC-MS ⁿ , mass spectrometry is used to identify the origin of the signal in the chromatogram (eg, from the photoinitiator). For example, in SEC, additional experiments, such as NMR, are necessary to further identify the origin of each signal observed in the chromatogram.

  Furthermore, a GC-MS technique similar to the LC-MS technique but with additional required standards and calibration can be used before analyzing the actual coating composition. Prior to utilizing the analytical techniques described above, chemical derivatization of the photoinitiator and / or other species and entities in the coating may be necessary. Atomic absorption measurement also provides an analytical tool for measuring coating compositions. In principle, any spectrograph and / or spectroscopic technique that can clearly distinguish the integrated signal can be selected to identify the functional group of a particular chemical and the photoinitiation present in the coating. Relative elemental composition can be used to determine the relative amount of agent. Before determining the relative amount of photoinitiator in the coating, several experiments summarized below should be performed.

  1. The degradation of the photoinitiator should be described as a result of both heating and UV-vis radiation, and possibly a combination thereof. The degradation information can be used to determine the amount of photoinitiator present in the coating prior to curing the coating.

  2. Diffusion of the photoinitiator present in the coating into the surrounding medium. More specifically, the diffusion of one or more photoinitiators present in the coating into an aqueous or highly polar medium as a function of time should be described. In addition, diffusion into non-polar media should be described. Given the hydrophilic coating contained in the medium and the time that the coating is contained, the diffusion data can be used to determine the amount of photoinitiator present in the coating prior to inclusion.

  Having the decomposition and diffusion data at hand allows the relative amount of photoinitiator moiety residues present in the coating to be determined prior to processing conditions.

Thus, the present invention is also a novel medical device comprising a thermoplastic substrate polymer medical device element, wherein the following covalently cross-linked (a) and (b): A medical device having a layer of a coated coating composition;
(A) one or more poly (ethylene oxide) as one or more polymer components optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein one of the above Or two or more poly (ethylene oxides) comprise at least 50% by weight of the one or more polymer components; and (b) one or more low-residues having a plurality of photoinitiator moiety residues. Molecular weight skeleton, wherein the photoinitiator moiety residues are the one or more poly (ethylene oxides), any non-thermoplastic hydrophilic polymer and one or more low molecular weight skeletons. Constitutes 0.01-20% by weight of the total amount;
Here, the coating composition is (co) extruded or injection molded with the thermoplastic base polymer, and the covalent crosslinking of the coating composition is one or two in the coating composition. Obtained as a result of the presence of more than one species of photoinitiator,
The photoinitiator moiety is covalently bonded to the low molecular weight backbone and / or covalently introduced into the backbone of the low molecular weight backbone by exposing the coating composition to UV or visible light. Has been.

The present invention is also a novel medical device including a prefabricated shaped article medical device element, wherein the following (a) and (b) covalent bonds are formed on the prefabricated shaped article: Further relates to a medical device having a layer of a coating composition crosslinked thereto;
(A) one or more poly (ethylene oxide) as one or more polymer components optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein one of the above Or two or more poly (ethylene oxides) comprise at least 50% by weight of the one or more polymer components; and (b) one or more low-residues having a plurality of photoinitiator moiety residues. Molecular weight skeleton, wherein the photoinitiator moiety residues are the one or more poly (ethylene oxides), any non-thermoplastic hydrophilic polymer and one or more low molecular weight skeletons. Constitutes 0.01-20% by weight;
Here, the coating composition is extruded or injection molded with the pre-fabricated shaped article, and the covalent crosslinking of the coating composition is one or two in the coating composition. It was obtained as a result of the above photoinitiator,
The photoinitiator moiety is covalently bonded to the low molecular weight backbone and / or covalently introduced into the backbone of the low molecular weight backbone by exposing the coating composition to UV or visible light. Has been.

The present invention further relates to a novel medical device comprising a prefabricated shaped medical device element, wherein the medical device has a layer of a thermoplastic base polymer on the prefabricated shaped product. The thermoplastic base polymer has a layer of the following covalently crosslinked coating composition of (a) and (b) on the thermoplastic base polymer;
(A) one or more poly (ethylene oxide) as one or more polymer components optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein one of the above Or two or more poly (ethylene oxides) comprise at least 50% by weight of the one or more polymer components; and (b) one or more low-residues having a plurality of photoinitiator moiety residues. Molecular weight skeleton, wherein the photoinitiator moiety residues are the one or more poly (ethylene oxides), any non-thermoplastic hydrophilic polymer and one or more low molecular weight skeletons. Constitutes 0.01 to 20% by weight of the total amount; wherein the coating composition is extruded or injection molded with the pre-fabricated shaped article; and the coating The covalent cross-linking of the composition is obtained as a result of one or more photoinitiators in the coating composition, and the photoinitiator moiety is capable of UV or visible light in the coating composition. To the low molecular weight backbone and / or covalently introduced into the backbone of the low molecular weight backbone.

  In view of the above considerations, the coating composition does not contain low molecular weight residuals of ethylenically unsaturated monomers.

Materials useful as the prefabricated shaped article, the thermoplastic substrate polymer, and as a component of the coating composition are as described above with respect to the method of the present invention.
Thus, in one embodiment, the thermoplastic base polymer is selected from the group consisting of polyurethane and PVC.

[material]
PEO Polyox WSR N-80 (M w 200kDa) and Polyox N-301 a (M _w 4MDa), was purchased from Dow. Irgacure 2959 was purchased from Ciba Specialty Chemicals (Basel, Switzerland). 97% BTDA was purchased from Alfa Aesar. 4-Benzoylbenzoic acid, 2-benzoylbenzoic acid and tert-butyl peroxybenzoate were purchased from Aldrich. CuCl was purchased from Fluka.

SMA 1000 (acid value 465-495 mg KOH / g sample, M _w 5500 g / mol), SMA 2000 (acid value 335-375 mg KOH / g sample, M _w 7500 g / mol), and SMA 3000 (acid value 265-305 mg KOH) / G sample, M _w 9500 g / mol) was purchased from Atofina. Boltorn H20 ( _Mn = 2100 g / mol, polydispersity index (PDI, Polydispersion Index) = 1.3), Boltorn H30 ( _Mn = 3500 g / mol, PDI = 1.5), and Boltorn H40 ( _Mn = 5100 g / mol, PDI = 1.8) was purchased from Perstorp.

1-methylimidazole and pyridine were purchased from Merck. Ethyl acetate, 2-propanol and acetone were purchased from Bie & Berntsen (Denmark). DMSO and thionyl chloride were purchased from Aldrich. Benzene was purchased from Fluka. Methyl isobutyl ketone (MIBK) was purchased from Baker. Dichloromethane was purchased from AppliChem. Jeffamine D-230 was purchased from Huntsman.
All percentages and parts are weight / weight% unless otherwise specified.

[Subjective evaluation of adhesion]
Friction and adhesion to the substrate were subjectively evaluated after swelling in water for at least 24 hours. The adhesion between the two layers was scored 1-4.
1. Complete delamination 1. 2. There is a large amount of poor adhesion and blistering. 3. Good adhesion, almost no blistering. Very good adhesion, smooth surface

[Subjective evaluation of gel aggregation]
Samples were immersed in deionized water for at least 24 hours. The adhesion of the UV cured coating to the Estane 58212 substrate was scored as shown in Example 1. At the same time, gel aggregation was scored on a subjective scale 1-6.

1 = not cross-linked; coating dissolved 2 = broken, very weak loose gel 3 = somewhat stable gel 4 = somewhat stable gel 5 = almost stable gel 6 = totally stable And binding gel

Example 1: Coating consisting of Irgacure 2959 and Polyox combined by SMA
[Synthesis of Irgacure 2959 ester of SMA 1000 (Compound 1)]
1.124 g SMA 1000 (4.81 mmol of anhydride based on a sample with an average acid number of 480 mg KOH / g) and 1.373 g of Irgacure 2959 (6.12 mmol) were dissolved in 12 g of acetone. . When 0.503 g of 1-methylimidazole (6.13 mmol) was added as a combined catalyst and base, the solution turned yellow. The mixture was stored at 70 ° C. in an airtight pressure-resistant glass bottle. The disappearance of the anhydride group from 1770-1860 cm ⁻¹ by FT-IR followed, and after 63 hours, the reaction was shown to be essentially complete (data not shown). Upon cooling, the solution became opaque and some precipitation was observed. The solution was acidified to pH 1-2 with HCl and Irgacure 2959 SMA 1000 acid ester was extracted with ethyl acetate.

  After drying of the ethyl acetate phase and evaporation of the solvent, a viscous, yellowish oil remained. The compound was dissolved in methanol, transferred to a tared Petri dish, placed in a ventilated heat dryer and dried at 70 ° C. for 80 minutes to give a viscous yellow compound; Met. No further work was done. Yield was 2.00 g. The theoretical amount of Irgacure 2959 in the polymer was 49 w / w-%. However, the maximum amount of Irgacure 2959 present in the preparation is 22 w / w − by UV-Vis spectroscopy under the assumption that the extinction coefficient of free Irgacure 2959 and bound Irgacure 2959 is the same. %. This was a higher estimate. This is because no correction was made for possible background absorption at the wavelength of maximum absorbance of Irgacure 2959. (274-5 nm in methanol and 1,3-dioxolane).

[Preparation of sample 1A: Irgacure 2959 bound to SMA 1000 in a gel composed of Polyox]
0.91 parts of Compound 1, 89.18 parts of Polyox N-301, and 9.91 parts of Polyox N-80 for 2 minutes at atmospheric pressure, then for 2 minutes under reduced pressure at 120 ° C. Mix in mixer. This mixture contained up to 0.20% Irgacure 2959. The mixture was hot pressed at 100 ° C. for 1 minute to form a circular slice having a thickness of 1 mm. A quarter of the slices were further hot pressed to the thinnest possible slice at 100 ° C. without spacers. Although the thickness was not measured regularly, it was 150 to 200 μm. A thin slice of Mixture 2 was laminated on a sheet of Estane 58212 that had been pre-wiped clean with ethanol for about 30-45 seconds at 100 ° C. and 50 bar (no spacer used). The sample was divided into two parts and both were heated to 60-80 ° C. for 5-10 minutes until clear. One sample was then immediately UV cured (1 minute) and the other sample was cured for 5 minutes at a distance of approximately 26 cm from a Fusion I600 H-lamp operating at 100% intensity. The samples were evaluated subjectively as described in the introduction of the experimental part.

[Synthesis of Irgacure 2959 ester of SMA 2000 (compound 2)]
1.428 g SMA 2000 (4.52 mmol of anhydride based on a sample with an average acid number of 355 mg KOH / g) and 1.151 g of Irgacure 2959 (5.13 mmol) were dissolved in 12 g of acetone. . When 0.421 g of 1-methylimidazole (5.13 mmol) was added, the solution turned yellow. The mixture was stored at 70 ° C. in an airtight pressure-resistant glass bottle. The disappearance of the anhydride group at 1770-1860 cm ⁻¹ followed by FT-IR showed that after 63 hours the reaction was 60-65% complete (data not shown). Thus, the reaction was slower than with SMA 1000. The solution is acidified to pH 1-2 with HCl and Irgacure 2959 SMA 2000 acid ester is filtered, dissolved in acetone, transferred to a tared petri dish and placed in a ventilated heat dryer. And dried at 70 ° C. for 170 minutes to give a predominantly hard crystalline material with some soft areas; this was Compound 2. No further work was done. The yield was 1.88g. The theoretical amount of Irgacure 2959 in the polymer was 41.5 w / w-%. However, the maximum amount of Irgacure 2959 present in the preparation was determined to be 11 w / w-% by UV-Vis spectroscopy.

[Preparation of Sample 1B: Irgacure 2959 bound to SMA 2000 in a gel composed of Polyox]
1.12 parts of compound 2, 88.99 parts of Polyox N-301, and 9.89 parts of Polyox N-80 at atmospheric pressure for 2 minutes and then under reduced pressure for 2 minutes at 120 ° C. Mix in mixer. This mixture contained up to 0.12% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Synthesis of Irgacure 2959 ester of SMA 3000 (compound 3)]
1.647 g SMA 3000 (4.18 mmol anhydride based on a sample with an average acid number of 285 mg KOH / g) and 0.991 g Irgacure 2959 (4.42 mmol) were dissolved in 12 g acetone. The addition of 0.363 g 1-methylimidazole (4.42 mmol) turned the solution yellow. The mixture was stored at 70 ° C. in an airtight pressure-resistant glass bottle. The disappearance of the anhydride group at 1770-1860 cm ⁻¹ followed by FT-IR showed that after 63 hours the reaction was 60-65% complete (data not shown). Thus, the reaction was slower than when SMA 1000 was used, but at about the same rate as SMA 2000. The solution was acidified to pH 1-2 with HCl and Irgacure 2959 SMA 3000 acid ester was extracted with methyl isobutyl ketone. After drying of the methyl isobutyl ketone phase and evaporation of the solvent, a yellow material remained. The compound was dissolved in acetone, transferred to a tared Petri dish, placed in a ventilated heated dryer and dried overnight at 70 ° C. to give a pale yellow, clear, crumbly glass. This was compound 3. No further work was done. The yield was 2.22g. The theoretical amount of Irgacure 2959 in the polymer was 36 w / w-%. However, the maximum amount of Irgacure 2959 present in the preparation is 25 w / w − by UV-Vis spectroscopy under the assumption that the extinction coefficients of free Irgacure 2959 and bound Irgacure 2959 are the same. %.

[Preparation of sample 1C: Irgacure 2959 bound to SMA 3000 in a gel composed of Polyox]
1.33 parts of Compound 3, 88.80 parts of Polyox N-301, and 9.87 parts of Polyox N-80 at atmospheric pressure for 2 minutes, then under reduced pressure for 2 minutes at 120 ° C. Mix in mixer. The mixture contained up to 0.33% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Results and Discussion Regarding Samples 1A to 1C]
The results are shown below.

  In samples with Polyox coating (1A-C), gel aggregation follows the following pattern: SMA 3000 (0.33% Irgacure 2959)> SMA 1000 (0.20% Irgacure 2959)> SMA 2000 (0.12) % Irgacure 2959). This order follows the concentration of Irgacure 2959 in the sample, while the order of the SMA polymers appears to be random. Thus, the concentration of Irgacure 2959 needs to be at least 0.3% to achieve good UV crosslinking of the gel, but the effect of the SMA type appears to be less.

  Sample 1C was UV cured for 5 minutes, resulting in a good gel that adhered strongly to the substrate. This effect can be attributed to the relatively low concentration of Irgacure 2959 in Sample 1C, which allows for better cure, or the effect is of Irgacure 2959 with SMA bound substrate and Polyox Can be attributed to particularly good compatibility with both.

Example 2: Coating consisting of Polyox and Irgacure 2959 bonded to an aliphatic, hydrophobic polyurethane
Compounds 4 and 5 were custom synthesized by Bomar Specialties Co (Winsted, CT) and distributed in Europe by IGM Resin (Walwijk, the Netherlands). Compound 4 was an intermediate molecular weight, aliphatic, trifunctional polyetherurethane functionalized with Irgacure 2959 at three ends. The content of Irgacure 2959 in compound 4 was 33.0 w / w-%, as shown by Bomar. Compound 5 was an intermediate molecular weight, aliphatic, linear polyether urethane functionalized with Irgacure 2959 at both ends. The content of Irgacure 2959 in Compound 5 was 15.5 w / w-%, as shown by Bomar. Neither compound contained any acrylate groups, as measured by FT-IR.

[Preparation of sample 2A: 1% compound 4 in a gel composed of Polyox]
1 part of compound 4, 89.1 parts of Polyox N-301 and 9.9 parts of Polyox N-80 in a Blender mixer at 120 ° C. for 2 minutes at atmospheric pressure, then for 2 minutes under reduced pressure. Mixed with. This mixture contained 0.33% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Preparation of sample 2B: 5% compound 4 in a gel composed of Polyox]
5 parts of compound 4, 85.5 parts of Polyox N-301, and 9.5 parts of Polyox N-80 in a Blender mixer at 120 ° C. for 2 minutes at atmospheric pressure and then for 2 minutes under reduced pressure. Mixed with. This mixture contained 1.65% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Preparation of sample 2C: 10% compound 4 in a gel composed of Polyox]
10 parts of Compound 4, 81 parts of Polyox N-301 and 9 parts of Polyox were mixed in a Blender mixer at 120 ° C. for 2 minutes at N-80 atmospheric pressure and then for 2 minutes under reduced pressure. This mixture contained 3.30% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Preparation of sample 2D: 1% compound 5 in a gel composed of Polyox]
1 part of compound 5, 89.1 parts of Polyox N-301 and 9.9 parts of Polyox N-80 at atmospheric pressure for 2 minutes, then under reduced pressure for 2 minutes at 120 ° C. in a Blender mixer. Mixed with. This mixture contained 0.16% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Preparation of sample 2E: 5% compound 5 in a gel composed of Polyox]
5 parts of compound 5, 85.5 parts of Polyox N-301 and 9.5 parts of Polyox N-80 in a Blender mixer at 120 ° C. for 2 minutes at atmospheric pressure and then for 2 minutes at reduced pressure. Mixed. This mixture contained 0.78% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Preparation of sample 2F: 10% compound 5 in a gel composed of Polyox]
10 parts of Compound 5, 81 parts of Polyox N-301 and 9 parts of Polyox N-80 were mixed in a Blender mixer at 120 ° C. for 2 minutes at atmospheric pressure and then for 2 minutes under reduced pressure. This mixture contained 1.55% Irgacure 2959. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Results and Discussion Regarding Samples 2A to F]
The results are shown below.

  Samples 2A-C produced a strong gel that adhered well to the substrate after 5 minutes of UV curing. Samples 2E-F also produced strong gels after 5 minutes of UV curing, but these gels did not adhere to the substrate. These experiments clearly demonstrate that the photoactive polymer geometry is more important for adhesion than the sheer concentration of photoinitiating groups in the gel. That is, the trifunctional photoactive polyurethane compound 4 strongly adhered the base polymer, while the bifunctional compound 5 did not strongly adhere the base polymer. It is also clear that 0.16% Irgacure 2959 (Sample 2D) in the gel is not sufficient to induce effective crosslinking of the gel, even after 5 minutes of UV curing, and this result is Also found for sample 1B.

Example 3: Coating consisting of Polyox with BTDA-Jeffamine condensation polymer as photoinitiator
[Synthesis of BTDA-Jeffamine D-230 condensation polymer (Compound 6)]
1.77 g 97% BTDA (5.33 mmol) was magnetically stirred and heated to 60 ° C. and dissolved in 12 g DMSO. 1.23 g of Jeffamine D-230 (5.35 mmol) was added with a significant exotherm. FT-IR recorded within minutes after mixing indicated that the reaction between dianhydride and diamine was instantaneous.

  The solution was acidified to pH 1-2 with HCl and the BTDA-Jeffamine D-230 condensation polymer was extracted with dichloromethane. The dichloromethane phase was dried and the dichloromethane was evaporated; this was compound 6. The above compound contained up to 11.4% BTDA, but cannot be confirmed by UV-Vis spectroscopy because of the large background absorption at the maximum absorption of BTDA (257 nm in ethanol). It was.

[Preparation of sample 3A: BTDA / Jeffamine D-230 condensation polymer as photoinitiator in a gel composed of Polyox]
1.73 parts of Compound 6, 88.44 parts of Polyox N-301, and 9.83 parts of Polyox N-80 at atmospheric pressure for 2 minutes, then under reduced pressure for 2 minutes at 120 ° C. Mix in mixer. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A. The sample contained up to 0.20% BTDA.

[Results and Discussion on Sample 3A]
The results are shown below.

  Despite using a low concentration of photoinitiator, a relatively strong gel was produced from Sample 3A after 1 minute of UV curing. However, the gel strength at 5 minutes UV curing was better.

Example 4: Coating consisting of Polyox with benzophenone bound to Boltorn as photoinitiator
[Synthesis of 4-benzoylbenzoyl chloride]
In a 100 mL round bottom flask, 5.00 g 4-benzoylbenzoic acid (22.1 mmol), 10.0 mL thionyl chloride (16.31 g, 137 mmol) and 1 drop of DMF were kept at 100 ° C. Reflux in an oil bath for 75 minutes. Gaseous SO ₂ and HCl streams produced during the reaction are directed through a rubber tube and glass pipette onto the surface of a 1M NaOH solution that is being vigorously stirred, where most of the gas is absorbed. And converted to sulfite and chloride. In consideration of the risk of sodium hydroxide being sucked back into the system, care was taken so that the tip of the glass pipette did not contact the surface of the sodium hydroxide solution.

After 75 minutes reflux, the oil bath was removed and the reaction mixture was cooled to room temperature. The condenser is removed and a portion of the rubber tube from the round bottom flask is directed to the inlet of the membrane pump and the outlet from the membrane pump is stirred through the rubber tube and glass pipette to 1M. In the direction of the NaOH solution. The glass pipette should be at a greater distance from the NaOH solution than in the first experiment. This is because the air flow through the pump is much larger than the natural flow of gaseous SO ₂ and HCl from the first experiment. Suction was then applied and the reaction mixture was gently heated in a warm oil bath for the first 10 minutes at room temperature and then for the next 10 minutes to remove unreacted SOCl ₂ . The flask with pearl, yellow, solid 4-benzoylbenzoyl chloride was stoppered until used in the next step of the synthesis. The membrane pump flushed free residual SOCl ₂ by drawing 500 mL of deionized water through the pump directly into one of the two small holes in the plastic bucket lid in the fume hood.

[Synthesis of Boltorn H-20 ester of 4-benzoylbenzoic acid (Compound 7)]
In a 250 mL round bottom flask with a directly attached distillation head, 2.43 g Boltorn H-20 (22.1 mmol OH based on a sample with an average OH number of 510 mg KOH / g) was added to 50 mL of pyridine. (48.9 g; 0.618 mol). The mixture was dried by heating and distilling a mantle with a magnetic stirrer. This is because water forms a low boiling azeotrope with pyridine (azeotrope boiling point 93.6 ° C .; the azeotrope contains 75.5 mol% water). As soon as the water was removed, the distillation temperature was raised to the boiling point of pure pyridine (ie 115.3 ° C.); from this point an additional 4-5 mL of pyridine / water was passed through a small funnel to the measuring cylinder. Gathered inside.

  A 100 mL addition funnel dried in a 130 ° C. heat dryer was placed on top of a 100 mL round bottom flask containing 4-benzoylbenzoyl chloride (see above). A warm anhydrous solution of Boltorn H-20 was transferred to the addition funnel and a nitrogen bubbler was attached to exclude moisture. 10-15 mL of Boltorn solution was added at a rate that only a small amount of gaseous HCl formed on the liquid; this should re-enable magnetic stirring in the flask. The remainder of the solution was added at a rate such that the temperature outside the flask did not exceed about 40 ° C. (no external cooling or heating, as judged by bare hands). The reaction mixture turned brown. If necessary, the solution was cooled in an ice bath. Towards the end of the Boltorn addition of the reaction mixture, the reaction mixture became darker due to the precipitation of pyridinium chloride that appeared light brown. After about 1 hour, the exotherm stopped and the reaction mixture was at room temperature as a sign that the reaction was complete.

Excess concentrated HCl was added to protonate all the pyridine to solubilize, and the Boltorn ester was extracted from the aqueous phase to 3 × 50 mL CH ₂ Cl ₂ . The organic extract was dried overnight with MgSO ₄ and the CH ₂ Cl ₂ was evaporated. The Boltorn H-20 ester of 4-benzoylbenzoic acid was a light brown hard solid. This was Compound 7.

[Preparation of sample 4A: Boltorn H-20 ester of 4-benzoylbenzoic acid as photoinitiator in a gel composed of Polyox]
1.45 parts of Compound 7, 88.695 parts of Polyox N-301, and 9.855 parts of Polyox N-80 for 2 minutes at atmospheric pressure, then for 2 minutes under reduced pressure at 120 ° C., Blender mixer Mixed in. The mixture was hot pressed, laminated, and UV cured for 1 minute and 5 minutes as described for Sample 1A. The sample was evaluated subjectively as described for sample 1A.

[Synthesis of Boltorn H-30 ester of 4-benzoylbenzoic acid (Compound 8)]
2.48 g Boltorn H-30 (22.1 mmol OH based on a sample with an average OH number of 500 mg KOH / g) was dissolved in 50 mL pyridine (48.9 g; 0.618 mol) and dried. And reacted with 4-benzoylbenzoyl chloride prepared from 5.00 g of 4-benzoylbenzoic acid (similar to that described in the synthesis of the Boltorn H-20 ester of benzoylbenzoic acid (compound 7)). The Boltorn H-30 ester of 4-benzoylbenzoic acid was a light brown waxy material. This was Compound 8.

[Preparation of sample 4B: Boltorn H-30 ester of 4-benzoylbenzoic acid as photoinitiator in a gel composed of Polyox]
1.46 parts of Compound 8, 88.69 parts of Polyox N-301, and 9.85 parts of Polyox N-80 are mixed at atmospheric pressure for 2 minutes, then under reduced pressure for 2 minutes at 120 ° C. Mix in mixer. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Synthesis of 2-benzoylbenzoyl chloride, batch no. 1 (abbreviated as “2-BBCl-1”)]
The synthesis of 2-BBCl-1 was performed similarly to the synthesis of 4-benzoylbenzoyl chloride (see above). However, 2-BBCl-1 was a yellow oil and not a solid like 4-benzoylbenzoyl chloride.

[Synthesis of Boltorn H-20 ester of 2-benzoylbenzoic acid (Compound 9)]
2.43 g Boltorn H-20 (22.1 mmol OH based on a sample with an average OH number of 510 mg KOH / g) was dissolved in 50 mL pyridine (48.9 g; 0.618 mol) and dried. And reacted with 2-BBCl-1 prepared from 5.00 g of 2-benzoylbenzoic acid as described above. The Boltorn H-20 ester of 2-benzoylbenzoic acid was a light brown hard solid. This was Compound 9.

[Preparation of sample 4C: Boltorn H-20 ester of 2-benzoylbenzoic acid as photoinitiator in a gel composed of Polyox]
1.45 parts of Compound 9, 88.695 parts of Polyox N-301, and 9.855 parts of Polyox N-80 for 2 minutes at atmospheric pressure, then for 2 minutes under reduced pressure at 120 ° C. Mix in mixer. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Synthesis of Boltorn H-30 ester of 2-benzoylbenzoic acid (Compound 10)]
2.48 g Boltorn H-30 (22.1 mmol OH based on a sample with an average OH number of 500 mg KOH / g) was dissolved in 50 mL pyridine (48.9 g; 0.618 mol), dried, Then, as described above, it was reacted with 2-BBCl-1 prepared from 5.00 g of 2-benzoylbenzoic acid. The Boltorn H-30 ester of 2-benzoylbenzoic acid was a light brown hard solid. This was Compound 10.

[Preparation of sample 4D: Boltorn H-30 ester of 2-benzoylbenzoic acid as photoinitiator in a gel composed of Polyox]
1.46 parts of Compound 10, 88.69 parts of Polyox N-301, and 9.85 parts of Polyox N-80 are mixed at atmospheric pressure for 2 minutes, then under reduced pressure for 2 minutes at 120 ° C. Mix in mixer. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Preparation of sample 4E: 2-benzoylbenzoic acid not bound to Boltorn H-20 in a gel composed of Polyox]
0.24 parts 2-benzoylbenzoic acid, 1.21 parts Boltorn H-20, 88.695 parts Polyox N-301, and 9.855 parts Polyox N-80 at atmospheric pressure. Mix in a Blender mixer at 120 ° C. for 2 minutes and then under reduced pressure. The mixture was hot pressed as described for Sample 1A, laminated, and UV cured for 1 minute and 5 minutes. The sample was evaluated subjectively as described for sample 1A.

[Results and Discussion on Samples 4A to 4E]
The results are shown below. :

  When comparing samples 4A-D with all bound photoinitiators, only 4-BBA (4A-B) ensures good adhesion of the coating to the substrate after 5 minutes UV curing of the Polyox-coating. On the other hand, it is clear that 2-BBA failed to ensure good adhesion (4C-D). On the other hand, 2-BBA produced a stronger Polyox gel than 4-BBA. Sample 4E with unbound 2-BBA and H-20 did not produce a strong gel after 1 minute of UV curing, in contrast to all other photoinitiator combinations in Polyox; H- It is clear that 20 acts minimally with the photoinitiator bound thereto.

[Example 5: Preparation of PEG4000 backbone carrying photoinitiator moiety]
4-Benzoylbenzoic acid (2.63 g, 11.6 mmol) was added to toluene (100 mL) and the mixture was heated to 45 ° C. Oxalyl chloride (1.85 g, 14.6 mmol) was added, followed by a few drops of DMF, and the reaction mixture was stirred at 45 ° C. overnight. After removing the solvent, the residue was further dissolved in toluene (100 mL), several lumps of CaH ₂ were added, and the mixture was stirred for 1 h at RT. The mixture was filtered and the solvent removed to leave the crude acid chloride and immediately dissolved in THF (100 mL). ^t BuOOH (2.5 mL, 5.5 M, 14 mmol in decane) and 30% KOH (3 mL, 16 mmol) were added simultaneously and the reaction mixture was stirred at RT overnight. 2M Na ₂ CO ₃ (50 mL) was added and the organic layer was separated and dried (MgSO ₄ ). Celite was then added and the solvent was removed.

The residual was placed on the column. Column chromatography with solvent elution with EtOAc and heptane left 1.6 g (46%) of tert-butyl 4-benzoylbenzoperoxoate as a slightly yellow oil; ¹ H- NMR (CDCl ₃ , RT): 8.05 (d, 2H, J = 8 Hz), 7.84 (d, 2H, J = 8 Hz), 7.79 (d, 2H, J = 8 Hz), 7.61 (T, 1H, J = 8 Hz), 7.49 (t, 1H, J = 8 Hz), 1.43 (s, 9H); ¹³ C-NMR (CDCl ₃ , RT): 195.6, 163.5 141.7, 136.7, 133.0, 130.7, 130.0, 129.8, 129.0, 128.4, 84.3, 26.2.

PEG 4000 (2 g) from Clariant was dissolved in benzene (200 mL) and freshly prepared CuCl (5 mg) was added. The solution was heated to reflux where tert-butyl 4-benzoylbenzoperoxoate (1 g, 3.4 mmol) dissolved in benzene (25 mL) was added as a drop and the reaction mixture was added for an additional 72 hours. Circulated. During the reaction, the color changed slightly from green to blue. After cooling to RT, the reaction was quenched with 2M Na ₂ CO ₃ (5 mL) followed by removal of water by distillation. The mixture was then filtered and the solvent was poured into heptane. After a period of time, an oily material formed at the bottom of the beaker and the remaining solvent was gently transferred to leave a benzophenone functional PEG; ¹ H-NMR and UV-vis measurements indicated a benzophenone loading of about 30% by weight. The FT-IR measurement, the two keto - band at 1718 cm ^-1 and 1645 cm ^-1 confirms the presence of the functional group was shown.

[Preparation of Sample 5A: Benzophenone bound to PEO in a gel composed of Polyox]
Compound 11 (4 parts), Polyox N-301 (88 parts) and Polyox N-80 (8 parts) were mixed in a Blender mixer at 120 ° C. for 10 minutes at atmospheric pressure. The mixture was then hot pressed at 120 ° C. Considering the benzophenone loading on the PEO skeleton, this mixture effectively contained about 1 w / w-% photoinitiator. For comparison, Polyox N-301 (89 parts), Polyox N-80 (10 parts), and benzophenone (1 part) were mixed under the same conditions as for the compound containing Compound 11. Finally, Polyox N-301 (90 parts) and Polyox N-80 (10 parts) compounds were prepared and hot pressed. Films of similar dimensions for all three compounds were dr. UV irradiation was performed using a Honle GmbH UV lamp. Upon curing, the temperature of the sample increased above the melting temperature for the film. The gel properties of the films were evaluated by placing them in a petri dish and covering them with water. Visual inspection showed that the film without both photoinitiator did not form a gel, while the film with both unbound benzophenone and benzophenone bound to the PEO skeleton produced a gel of similar strength. Represented.

[Example 6: Irgacure 2959 bound to PEO 1NF and aliphatic, hydrophobic polyurethane from Sumitomo (150-400 kDa)]

These ingredients were mixed in a twin screw extruder. The ingredients were fed to the extruder by a gravimetric feeder, extruded into strands and pelletized.
The extruder profile was as follows.

  Two single screw extruders were then connected to a single crosshead dual tube die. Extruder No. 1 and Extruder No. Both were charged with Compound A. The blend was extruded onto a pre-made tube of Estane 58212 and a single layer was formed using a speed of 15 m / min. The same procedure was repeated with compounds B, C and D, and thin monolayers were formed and in-line UV cured with Fusion 600I H-lamp at 80 and 100% strength.

The ratio of the inner layer to the outer layer was varied by adjusting the output either to speed up the extruder or to reduce the screw speed. The layer thickness was prepared by changing either the output or the take-off device.
The two extruders had the same temperature profile.

  After extrusion, the coated tube was cut into a 35 cm long sample. UV cured samples were allowed to swell in 0.9% saline for at least 24 hours. The adhesion of the above layers to the tube and gel aggregation were subjectively evaluated.

  The first three compounds improved adhesion to the tube when UV cured at the highest intensity. Compound A, which has the lowest amount of Irgacure 2959 bound to an aliphatic, hydrophobic polyurethane, required the highest UV intensity in order to adhere acceptable to the tube. Compound D, which had the highest amount of Irgacure 2959 bound to an aliphatic, hydrophobic polyurethane, cured with much lower UV intensity and was able to adhere reasonably to the tube.

Claims (16)

A method for preparing a medical device element comprising the following steps;
(I) providing a prefabricated shaped article and / or a thermoplastic base polymer;
(Ii) providing a coating composition comprising:
(A) one or more poly (ethylene oxide) as one or more polymer components, optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein said one Or two or more poly (ethylene oxide) comprises at least 50% by weight of the plurality of polymer components; and (b) one or more low molecular weight skeletons covalently bonded to the low molecular weight skeletons And / or a low molecular weight backbone having a plurality of photoinitiator moieties covalently introduced into the low molecular weight backbone, wherein the photoinitiator moiety is one or more of the above Constitutes 0.01-20% by weight of the total amount of poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and the one or more low molecular weight skeletons;
(Iii) a coating composition of step (ii) is previously applied on the prefabricated shaped article and / or thermoplastic substrate polymer of step (i) and having a layer of said coating composition thereon Extruding, injection molding or powder coating to provide a fabricated shaped article and / or a medical device element of the base polymer, wherein the pre-made shaped article and the base When both material polymers are present, the prefabricated shaped article has a layer of the base polymer on the prefabricated shaped article:
(Iv) irradiating the coating composition with UV or visible light so as to covalently crosslink the coating composition.   The method of claim 1, wherein the one or more poly (ethylene oxide) is the only polymer component of the composition.   The method of claim 1, wherein the polymer component is one or more poly (ethylene oxide) in combination with one or more non-thermoplastic hydrophilic polymers.   The one or more non-thermoplastic hydrophilic polymers are selected from the group consisting of poly (N-vinylpyrrolidone), poly (acrylic acid), polyoxazoline, and copoly (methyl vinyl ether / maleic anhydride). The method according to claim 3.   The method according to any one of claims 1 to 4, wherein the skeleton is selected from polyethylene glycol, poly (styrene-co-maleic anhydride), aliphatic polyether urethane, polyetheramine and polyester.   The method according to any one of claims 1 to 5, wherein a weight average molecular weight of the skeleton is in a range of 100 to 10,000 Da (g / mol).   7. The poly (ethylene oxide) according to claim 1, wherein the poly (ethylene oxide) has an average molecular weight in the range of 100,000 to 8,000,000 Da, in particular in the range of 200,000 to 4,000,000 Da. Method. The coating composition is:
20 to 99.99% by weight of said one or more poly (ethylene oxide) (PEO);
0-10% by weight of one or more plasticizers;
0.01 to 80% by weight of the one or more low molecular weight skeletons; and 0 to 5% by weight of other components:
The method according to claim 1, comprising: The coating composition is:
40-94% by weight of said one or more poly (ethylene oxide) (PEO);
5 to 30% by weight of the one or more non-thermoplastic hydrophilic polymers;
0-10% by weight of one or more plasticizers;
1 to 40% by weight of the one or more low molecular weight skeletons; and 0 to 5% by weight of other components:
The method according to claim 1, comprising: A prefabricated shaped article is prepared in step (i), and step (iii) comprises applying the coating composition of step (ii) over the prefabricated shaped article of step (i) 10. Extruding, injection molding or powder coating to provide said pre-fabricated shaped medical device element having a layer of said coating composition thereon. The method as described in any one of. A thermoplastic base polymer is provided in step (i), and step (iii) comprises the coating composition of step (ii) together with the thermoplastic base polymer of step (i), the layer of said coating composition. 10. A method according to any one of the preceding claims comprising extruding or injection molding to provide a medical device element of the thermoplastic substrate polymer thereon. A pre-fabricated shaped article and a thermoplastic substrate polymer are prepared in step (i), and step (iii) together with the thermoplastic substrate polymer of step (i) On top of the article, the coating composition of step (ii) is extruded, injection molded or powdered to provide the prefabricated shaped article medical device element and the thermoplastic substrate polymer Including coating,
The prefabricated shaped article has a layer of the thermoplastic base polymer thereon, and the thermoplastic base polymer has a layer of the coating composition thereon;
The method according to any one of claims 1 to 9. A medical device comprising a medical device element of a thermoplastic base polymer,
A medical device having a layer of the following covalently cross-linked coating composition of (a) and (b) on the thermoplastic base polymer;
(A) one or more poly (ethylene oxide) as one or more polymer components, optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein said one Or two or more poly (ethylene oxides) comprise at least 50% by weight of the plurality of polymer components; and (b) one or more low molecular weight backbones having residues of a plurality of photoinitiator moieties. Where the residue of the photoinitiator moiety is the total amount of the one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and the one or more low molecular weight skeletons. 0.01 to 20% by weight of
Wherein the coating composition is (co) extruded or injection molded with the thermoplastic base polymer, and the covalent crosslinking of the coating composition is one or two in the coating composition. Obtained as a result of the presence of more than one species of photoinitiator,
The photoinitiator moiety is covalently bonded to the low molecular weight backbone and / or covalently introduced into the backbone of the low molecular weight backbone by exposing the coating composition to UV or visible light. Has been. A medical device comprising a prefabricated shaped medical device element,
A medical device having a layer of the following covalently cross-linked coating composition of (a) and (b) on the pre-fabricated shaped article;
(A) one or more poly (ethylene oxide) as one or more polymer components, optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein said one Or two or more poly (ethylene oxides) comprise at least 50% by weight of the plurality of polymer components; and (b) one or more low molecular weight backbones having residues of a plurality of photoinitiator moieties. Where the residue of the photoinitiator moiety is the total amount of the one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and the one or more low molecular weight skeletons. 0.01 to 20% by weight of
Here, the coating composition is extruded or injection molded with the pre-fabricated shaped article, and the covalent crosslinking of the coating composition is one or two in the coating composition. Obtained as a result of more than one species of photoinitiator,
The photoinitiator moiety is covalently bonded to the low molecular weight backbone and / or covalently introduced into the backbone of the low molecular weight backbone by exposing the coating composition to UV or visible light. Has been. A medical device comprising a prefabricated shaped medical device element,
A medical device having a layer of a thermoplastic base polymer on the prefabricated shaped article;
Here, the thermoplastic base polymer is the following (a) and (b) on the thermoplastic base polymer:
(A) one or more poly (ethylene oxide) as one or more polymer components, optionally combined with one or more non-thermoplastic hydrophilic polymers, wherein said one Or two or more poly (ethylene oxides) comprise at least 50% by weight of the plurality of polymer components; and (b) one or more low molecular weight backbones having residues of a plurality of photoinitiator moieties. Where the residue of the photoinitiator moiety is the total amount of the one or more poly (ethylene oxide), any non-thermoplastic hydrophilic polymer and the one or more low molecular weight skeletons. 0.01 to 20% by weight of
A layer of a covalently crosslinked coating composition,
The coating composition is (co) extruded or injection molded with the pre-fabricated shaped article and the thermoplastic substrate polymer, and the covalent crosslinking of the coating composition is performed by the coating composition Obtained as a result of one or more photoinitiators in the product,
The photoinitiator moiety is covalently bonded to the low molecular weight backbone and / or covalently introduced into the backbone of the low molecular weight backbone by exposing the coating composition to UV or visible light. Has been.   The medical device according to any one of claims 13 to 15, wherein the coating composition does not contain a low molecular weight residue of an ethylenically unsaturated monomer.

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