MXPA06006230A - Novel prepolymers for improved surface modification of contact lenses - Google Patents

Abstract

Provided are novel reactive functionalized fumaric- and itaconic-containing prepolymers and compositions comprising the prepolymers used in the manufacture of medical devices. The prepolymers can be used to provide surface modified contact lenses formed from one or more fumaric- or itaconic-containing prepolymers having reactive functionality that is complimentary to reactive, hydrophilic polymers.

Description

NEW PREPOLIMEROS FOR IMPROVED MODIFICATION OF THE SURFACE OF CONTACT LENSES FIELD OF THE INVENTION The present invention relates in general to novel reactive prepolymers containing fumaric and itaconic and to compositions comprising the prepolymers used in the manufacture of medical devices. More specifically, the present invention relates to fumaric and itaconic-containing prepolymers having reactive functionality provided by radicals possessing at least one reactive functional group. The prepolymers are useful in the manufacture of medical devices with modified surface such as contact lenses.

BACKGROUND OF THE INVENTION For many years the development of medical devices, such as contact lenses, made of materials containing silicone has been studied. These materials can be subdivided in general into two main classes which are hydrogels and non-hydrogels. Non-hydrogels do not absorb appreciable amounts of water, while hydrogels can absorb and retain water in a state of equilibrium. Hydrogels generally have a water content between about 15 and about 80 weight percent. Regardless of their water content, medical silicone devices of both non-hydrogel and hydrogel tend to have non-wettable, relatively hydrophobic surfaces, which have a high affinity for lipids. This problem concerns in particular the contact lenses. Monomers containing fumarate and fumaramide and compositions comprising the monomers have been developed to produce highly oxygen permeable hydrogels which can be used to make biomedical devices including contact lenses. Examples of these monomers and compositions containing fumarate and fumaramide can be found in U.S. Patent Nos. 5,374,662, 5,420,324 and 5,496,871, the contents of which are incorporated herein by reference. Due to the polar character of the amide function, this kind of monomer shows good compatibility with both hydrophobic monomers such as tris (tri ethylsiloxy) silane (TRIS) and hydrophilic monomers such as N. N-dimethylacrylate ida (DMA). These prepolymers of prior art give silicone hydrogels with excellent oxygen permeability and mechanical properties. However, like other silicone hydrogels, they are not sufficiently wettable to be useful as continuous use lenses unless their surface is treated. The structure and composition of the surface determine many of the physical properties and ultimate uses of solid materials. Characteristics such as wetting, friction and adhesion or lubricity are greatly influenced by the characteristics of the surface. The alteration of surface characteristics is of special significance in biotechnical applications where biocompatibility is a matter of importance. Therefore, those skilled in the art have long seen the need to render the surface of contact lenses and other medical devices hydrophilic, or more hydrophilic. By increasing the hydrophilicity of the surface of contact lenses, it improves the wettability of the contact lenses with the tear fluid of the eye. This, at the same time, improves the comfort of wearing contact lenses. In the case of continuous use lenses, the surface is especially important. The surface of a continuous use lens should be designed not only to be comfortable but also to avoid adverse reactions such as corneal edema, inflammation or infiltration of lymphocytes. Accordingly, improved methods for modifying the surfaces of contact lenses have been sought, in particular high Dk lenses (highly oxygen permeable lenses) designed for continuous (overnight) use. There are several patents that describe the union of hydrophilic polymer chains, or otherwise biocompatible, to the surface of contact lenses to make the lens more biocompatible. For example, published U.S. Patent No. 2002/0102415 Al indicates a plasma treatment of a substrate containing fumarate or fumaramide followed by reaction with other polymers such as DMA / VDMO copolymer. Although manufacturing steps such as plasma treatment provide lenses having suitable coatings, it would be desirable to provide polymers with functionality complementary to that of the reactive hydrophilic polymers to produce a treated surface lens without the need for plasma treatment or corona discharge treatment.

SUMMARY OF THE INVENTION According to the present invention, new reactive functionalized prepolymers containing fumaric and itaconic are described to be used both with polymeric systems containing silicone and with polymeric systems that do not contain silicone used for biomedical devices, especially contact lenses. The new prepolymers have the following schematic representations: YCO-CH = CHCOW (R?) N (SiR2R30) m (SiR2R3) (Ri) nWOCCH = CH-COY and CH2 = C (CH2COY) COW (R?) N (SiR2R3?) M (S iR2R3) (Ri) n OC (CH2COY) C = CH2 where Ri is an alkyl di-radical which may have ether linkages, R2 and R3 are, independently, alkyl or phenyl groups, unsubstituted or substituted by halogen and ether linkages, is 0 or NH, n is an integer between 1 and 10, m is an integer between 2 and 200, and Y is a radical having a reactive functional group selected from the group consisting of functional groups hydroxyl, carboxyl, oxazolone, epoxy and anhydride provided that when W is Or, and it's not a radical of diethanolamine. The reactive functional group has complementary reactivity to reactive hydrophilic coating polymers. The invention further relates to medical devices made of a polymerizable mixture comprising the new prepolymers containing reactive functionalized fumaric and itaconic. These devices can be manufactured as modified medical devices on their surface without using treatments such as plasma treatment or corona discharge treatment.

DETAILED DESCRIPTION OF THE INVENTION As set forth above, the present invention is directed toward novel reactive prepolymers containing fumaric and itaconic for use with copolymerizable polymer systems employed for biomedical devices, especially contact lenses. As used herein, fumaric refers to a fumaric acid derivative and can be a fumarate (an ester), a fumaramide (an amide) or a radical having an ester function and an amide function. The fumaric group is a radical of trans-1,2-ethylenedicarboxylate. Therefore, it will be understood that the diastereoisomer of fumarate, aleate, is also included in the prepolymers of the present > invention containing fumaric. Itaconic refers to itaconic acid derivatives and has a similar meaning to fumaric acid. In other embodiments of the present invention, the new prepolymers are used in the manufacture of biomedical devices and are useful in contact lens formulations which may be "soft" or "hard" and which are preferably hydrogels. As is known in this area, certain cross-linked polymeric materials can be polymerized to form a hard, water-free xero-gel. The xerogels are considered dehydrated hydrogel formulations. It has been found that these xerogels can be physically altered to impart, for example, optical properties through machining and then be hydrated and retain their water content. When the term "polymerization" is used herein, it means polymerization of the double bonds of the monomers and prepolymers capped with polymerizable unsaturated groups that give rise to a three-dimensional network of cross-linking. In addition, notations such as "(meth) acrylate" or "(meth) acrylamide" are used herein to denote optional methyl substitution. Thus, for example (meth) acrylate includes both acrylate and methacrylate and N-alkyl- (meth) acrylamide includes both N-alkyl acrylamide and N-alkyl methacrylamide. The term "prepolymer" refers to high molecular weight monomer containing polymerizable groups. The monomers added to the monomer mixture of the present invention can therefore be low molecular weight monomers or prepolymers. According to this, it is understood that a term such as "silicone-containing monomers" include "silicone-containing prepolymers". The terms "articles shaped to be used in bio-medical applications" or "biomedical devices or materials" or "biocompatible materials" means that the hydrogel materials described herein have physico-chemical properties that make them suitable for prolonged contact with living tissues., sancre and mucous membranes. Although the present invention contemplates the use of new functionalized reactive prepolymers containing fumaric and itaconic for medical devices, including "hard" and "soft" contact lenses, the formulations containing the functionalized pre-polymerized reagents containing fumaric and itaconic of the present invention they are considered especially useful as soft hydrogel contact lenses. As understood in this area, a lens is considered sufficiently "soft" if it can bend on itself without breaking. A hydrogel is a hydrated cross-linked polymer system that contains water in a state of equilibrium. Silicone hydrogels (ie, silicon-containing hydrogels) are usually prepared by polymerizing a mixture containing at least one silicone-containing monomer and at least one hydrophilic monomer. By the term "silicone" it is meant that the material is an organic polymer comprising at least five percent by weight of silicone (-OSi- bonds), preferably 10 to 100 percent by weight of silicone, more preferably 30 to 90 percent. of sylicon. Applicable monomer units containing silicone for use in the formation of silicone hydrogels are well known in the art and in U.S. Patent Nos. 4,136,250, 4,153,641, 4,70,533, 5,034,461.; 5,070,215; 5,260,000; 5,310,779 and 5,358,995 are numerous examples. The reactive functionalized prepolymers containing fumaric and itaconic of the present invention have at least one fumaric group or an itaconic group. The monomer mixtures which form the novel prepolymers of the present invention can comprise both thermoinitiators and photoinitiators for curing purposes. The monomer mixtures may further comprise at least one additional hydrophilic monomer. In addition, the monomer mixture can additionally comprise at least one silicone-containing monomer. The fumaric and itaconic-containing prepolymers of the present invention are prepared by synthesis in a manner well known in the art and according to the examples described hereinafter. The functionalized prepolymers containing fumaric and itaconic of the present invention are incorporated into the monomer mixture. The relative weight percentage of the functionalized prepolymers containing fumaric and itaconic compared to the weight percentage of the total monomer mixture is from about 10% to 80%, more preferably from about 10% to 50%, and most preferably about 15%. % to 40%. Examples of hydrophilic monomers include, but are not limited to, lactam-containing ethylenically unsaturated monomers such as N-vinyl pyrrolidinone; methacrylic and acrylic acids; alcohols substituted with (meth) acrylic such as 2-hydroxyethylmethacrylate (HEMA) and 2-hydroxyethyl acrylate; Y (meth) acrylamides, such as methacrylamide and N, N-dimethylacrylamide (DMA); vinyl carbonate or vinyl carbamate monomers such as those described in U.S. Patent No. 5,070,215; and oxazolidone monomers such as those described in U.S. Patent No. 4,910,277. Other hydrophilic monomers such as glycerin methacrylate and polyethylene glycol monomethacrylate are also useful in the present invention. Preferred hydrophilic vinyl-containing monomers that can be incorporated into the hydrogels of the present invention include monomers such as N-vinyl lactams such as N-vinylpyrrolidinone (NVP), N-vinyl-N-methyl acetamide, N-vinyl-N -ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, with NVP being preferred in the first place. Preferred hydrophilic acrylic-containing monomers that can be incorporated into the hydrogel of the present invention include hydrophilic monomers such as N, N. dimethyl acrylamide (DMA), 2-hydroxyethyl methacrylate, glycerin methacrylate, 2-hydroxyethyl methacrylamide, methacrylic acid and acrylic acid, with DMA being the most preferred. Other suitable hydrophilic monomers will occur to anyone skilled in the art. The relative weight percentage of hydrophilic monomer (s) to total weight percentage of the comonomer mixture is preferably from about 5% to 80%, more preferably from about 20% to 70%, and most preferably from about 20% % to 40%. As mentioned above, the additional silicone-containing monomers may be present in the monomer mixtures with the reactive functionalized monomers containing fumaric or itaconic. A preferred class of suitable silicone-containing monomers that can be incorporated into the monomer mixture with the fumaric or itaconic-containing reactive functionalized prepolymers of the present invention are the bulky polysiloxane alkyl (meth) acrylic monomers represented by the following formula (I) ).

R 1.6 1S O e H, C: I C "-X (CH2) r Si Si- 16 or II I or R. 16 R I.B Si- 16 where: X is O or NR; each R 5 is, independently, hydrogen or an alkyl group having 1 to 10 carbon atoms; and every Rio is, independently, a lower alkyl group or phenyl group; and f is 1 or 3 to 10. These bulky monomers include ethacryloxypropyl tris (trimethylsiloxy) silane (TRIS), pentamethyldisiloxanylmethyl methacrylate, tris (trimethylsiloxy) methacryloxy propylsilane, phenyltetramethyldisiloxanethyl acrylate and methyldi (trimethylsiloxy) methacryloxymethyl silane. Other preferred classes of silicone-containing monomers that can be incorporated into a mixture of monomers with the functionalized reactive monomers containing fumaric. or itaconic of the present invention are the poly (organosiloxane) represented by the following formula (II): 23 ^ 25 ^ 23 A (27) Yes [O-Sn O Si (R-.) A ^ 24 R '26 R24 i ») wherein: A is an activated unsaturated group, such as an ester or amide of an acrylic acid or a methacrylic acid; each of R23-R28 is independently selected from the group consisting of a monovalent hydrocarbon radical or a monovalent hydrocarbon radical substituted with halogen, having 1 to 18 carbon atoms which may have ether bonds between carbon atoms, R27 is a divalent hydrocarbon radical having 1 to 22 carbon atoms, and n is 0 or an integer greater than or equal to 1. When monomers containing siloxane, other than the new silicone-containing prepolymers, are incorporated into the monomer mixture, the % by weight of the other siloxane-containing monomers, compared to the weight percent of total monomer mixture, is from about 5% to 60%, more preferably from about 10% to 50% and most preferably from 10% to 40%. %. Both the silicone-containing monomer, the functionalized prepolymer containing fumaric or itaconic, or the hydrophilic monomer can function as a cross-linking agent (a crosslinker), being defined as a monomer that has multiple polymerizable functions. In addition, crosslinkers may also be present in the monomer mixture that polymerizes to form the hydrogel. Most "known" crosslinking agents are hydrophobic. When it is desirable to incorporate both an acrylic-containing monomer and a vinyl-containing monomer to the silicone-containing polymer of the present invention, another cross-linking agent having both vinyl group and polymerizable acrylic group can be used, since the vinyl and acrylic monomers they have different reactivity ratios and may not be effectively copolymerized. Such crosslinkers facilitating the copolymerization of these monomers are the subject of U.S. Patent No. 5,310,779, the contents of which are incorporated herein by reference. These crosslinkers are represented by the following schemes: Aa . "if bs and where V denotes a group containing vinyl having the formula; II or A represents a group containing acrylic having the formula: ^ 35 ^^ 36 c = c / \ • Z C R37 or II S represents a group containing styrene having the formula: wherein R31 is an alkyl radical derived from substituted or unsubstituted hydrocarbons, alkylene poly oxide, poly (perfluoro) alkylene oxide, dialkylated polydimethylsiloxane, dialkylaminated polydimethylsiloxane modified with fluoroalkyl or fluoroether groups; R32-R0 are, independently, H or alkyl of 1 to 5 carbon atoms; Q is an organic group containing aromatic fractions having 6-30 carbon atoms; X, Y and Z are, independently, O, NH or S; v is 1, or higher; and a., s_ are, independently, greater than or equal to 0; and a + s is greater than or equal to 1. An example is carbonate or 2-hydroxyethyl methacrylate vinyl carbamate. Other crosslinking agents that can be incorporated into the silicone-containing hydrogel of the present invention include polyvinyl, typically di- or tri-vinyl monomers, most commonly the di- or tri (methacrylates) of dihydro-ethylene glycol, triethylene glycol, butylene glycol, hexane-1, 6-diol, thio-diethylene glycol diacrylate and thio-diethylene glycol methacrylate, neopentyl glycol diacrylate; trimethylolpropane triacrylate and the like; N, -dihydroxyethylene-bisacrylamide and bismetacrilamides; also diallyl compounds such as diallyl phthalate and triallyl cyanurate; divinylbenzene; ethylene glycol divinyl ether; and the (meth) acrylate esters of polyalcohols such as triethanolamine, glycerin, pentaerythritol, butylene glycol, mannitol and sorbitol. Other examples include N, N.methylene-bis- (meth) acrylamide, divinylbenzene sulphonated, and divinyl sulfone. Also useful are the reaction products of hydroxyalkyl (meth) acrylates with unsaturated isocyanates, for example the reaction product of 2-hydroxyethyl methacrylate with 2-isocyanatoethyl methacrylate (IEM). See U.S. Patent No. 4,954,587. Other known crosslinking agents are polyether-bibuthane dimethacrylate dimethacrylates (see US Patent No. 4,192,827), and crosslinkers obtained by the reaction of polyethylene glycol, polypropylene glycol and polytetramethylene glycol with 2-isocyanatoethyl methacrylate (IEM) or isocyanates. of m-isopropenyl- ?,? -dimethylbenzyl (-TMI) and polysiloxane-bibuthane-dimethacrylates. See U.S. Patent Nos. 4,486,577 and 4,605,712. Still other known crosslinking agents are the reaction products of polyvinyl alcohol, ethoxylated polyvinyl alcohol or polyvinyl alcohol-co-ethylene with 0.1 to 10 mole% of vinyl isocyanates such as IEM or -TMI. The prepolymers of the present invention, when copolymerized, readily cure to molded shapes by methods such as UV polymerization, use of thermal free radical initiators and heat ", or combination of both., representative free radicals, are organic peroxides, such as, for example, acetyl peroxide, lauroyl peroxide, decanoyl peroxide, stearoyl peroxide, benzoyl peroxide, tertiary butyl peroxypivalate, peroxydicarbonate, and commercially available thermal initiators. such as LUPERSOL® 256, 225 (Atofina Chemicals, Philadelphia, Pennsylvania) and the like, employed at a concentration of about 0.01 to 2 weight percent on the total monomer mixture. Representative UV initiators are those known in the art such as benzoin methyl ether, ethyl benzoin ether, DAROCUR®-1173, 1164, 2273, 1116, 2959, 3331, IGRACURE® 651 and 164 (Ciba Specialty Chemicals, Ardsley, New York). In addition to the aforementioned polymerization initiators, the copolymer of the present invention may also include other components that will be clear to those skilled in the art. For example, the monomer mixture may include additional dyes, or UV absorbing agents and curing agents such as those known in the contact lens art. The resultant copolymers of this invention can be formed as contact lenses by centrifugal molding processes such as those described in U.S. Patent Nos. 3,408,429 and 3,496,254, static molding processes such as those described in US Pat. U.S. Patent 5,271,875 and other conventional methods, such as compression molding as described in U.S. Patent Nos. 4,084,459 and 4,197,266. The polymerization of the monomer mixture can be carried out either in a spin mold or in a stationary mold which corresponds to the contact lens shape. The contact lens thus obtained can also be subjected to a mechanical finish if the occasion demands. In addition, the polymerization can be carried out in an appropriate mold or vessel to give a lens material in the form of a button, plate or rod, which can then be processed (for example, cut or polished with a lathe or laser) to obtain a contact lens of the desired shape. The hydrogels produced by the present invention carry oxygen, are hydrolytically stable, biologically inert, and transparent. The monomers and prepolymers employed in accordance with this invention are easily polymerized to form three dimensional lattices that allow oxygen transport and are optically transparent, strong and hydrophilic. The present invention provides materials that are useful in the manufacture of prostheses such as heart valves and infra-ocular lenses, such as contact lenses or as films. More particularly, the present invention is directed to contact lenses. The present invention further provides articles of manufacture that can be used for biomedical devices, such as surgical devices, heart valves, vessel substitutes, intrauterine devices, membranes and other films, diaphragms, surgical implants, blood vessels, artificial ureters, breast tissues. artificial and membranes intended to be brought into contact with body fluid outside the body, for example, dialysis membranes of the kidney and heart / lung machines and the like, catheters, mouth guards, denture linings, infra-ocular devices and especially contact lenses. It is known that blood, for example, degrades rapidly when it comes in contact with artificial surfaces. For prostheses and devices used with blood, it is necessary to design a synthetic surface that is antithrombogenic and non-hemolytic. The prepolymers of the present invention are useful in methods of modifying contact lens surfaces and similar medical devices through the use of complementary reactive functionality. Although from now on contact lenses will only be cited for the purpose of simplifying, this reference is not to be understood as limiting since the subject method is suitable for modifying the surface of other medical devices as well as for contact lenses. The reactive hydrophilic polymers are used "to form covalent chemical bonds with the surface of the contact lenses made from the novel functionalized, fumaric and itaconic-containing reactive prepolymers of the present invention." Preferred hydrophilic reactive polymers for use herein invention are selected on the basis of the specific reactive functionalized polymeric material that is coated.In accordance with the present invention, the one or more reactive hydrophilic polymers selected for surface modification must have chemical functionality complementary to that of polymerized functionalized reagent materials containing fumaric and This complementary chemical functionality allows the chemical reaction between the functionalized polymeric reagent material containing fumaric and itaconic and the reactive hydrophilic polymer to form covalent chemical bonds between them In this way, one or more hydrophilic reactive polymers are chemically bound to the surface of one or more functionalized polymeric reactive materials containing fumaric and itaconic from the contact lenses or similar medical device to achieve surface modification thereof. For the modification of the surface of the contact lenses according to the present invention, a complementary reactive function is incorporated between the new functionalized pre-polymerized prepolymers containing fumaric and itaconic from the material of the contact lenses and the surface modification treatment polymer. (SMTP). For example, if a reactive hydrophilic SMTP has epoxide function, then the contact lens material to be treated should have a functionalized prepolymer containing fumaric or itaconic that has a radical with complementary functionality that will react with that of SMTP. In this case, the contact lens material could include a reactive functionalized prepolymer containing fumaric such as bis-o_, γ-fumaryl butyl polydimethyl siloxane, diacid to react with the SMTP epoxide functionality. Also, if a contact lens is formed from a functionalized material containing fumaric having a radical that provides reactive epoxide, a hydrophilic SMTP containing a copolymer of 2-hydroxyethyl methacrylate can be used for modification of the surface with the present invention. Examples of complementary functionality are given in Table 1. TABLE I Alcohol, acrboxylic acid, amine Epoxide More specifically, surface modification of contact lenses having reactive functionalized copolymers containing fumaric and itaconic according to the present invention requires one or more reactive, hydrophilic SMTPs. The reactive hydrophilic STMPs useful in the practice of the present invention are copolymers of various hydrophilic monomers with a monomer having reactive chemical functionality. The hydrophilic monomers can be of the aprotic type such as acrylamides and N-vinyl pyrrolidinone or protic types such as methacrylic acid and 2-hydroxyethyl methacrylate. Examples of suitable hydrophilic monomers include, but are not limited to, N, -dimethylacrylamide, N, N-dimethylmethacrylamide, N-methylmethacrylamide and N-methylacrylamide, but preferably N, N-dimethylacrylamide for increased hydrophilicity. Suitable monomers having reactive chemical functionality include, for example, but not limited to, monomers having an epoxide, carboxylic acid, anhydride, oxazolone and alcohol function. Examples of suitable reactive hydrophilic SMTP include, but are not limited to, copolymers and terpolymers of the monomers having reactive chemical functionality described above. These reactive hydrophilic SMTPs are produced by free radical polymerization techniques known to those skilled in the art. Although the guidelines of the present invention preferably apply to soft or flexible contact lenses or medical devices made of flexible or compressible material, the invention can be applied to harder, less flexible lenses, formed of a relatively rigid material such as poly ( methyl methacrylate) (PMMA). In accordance with the present invention, functionalized reactive prepolymers containing fumaric and itaconic are used to produce contact lenses containing reactive functional groups. One or more reactive hydrophilic SMTPs are then selected, as described above, to have chemical functionality complementary to that of the reactive functionalized prepolymers containing fumaric and itaconic which form the contact lens. These complementary chemical functions allow a chemical reaction to take place between the functional groups of the reactive functionalized propolymer having fumaric and itaconic which forms the contact lens and the functional groups of one or more reactive hydrophilic SMTPs. This chemical reaction between functional groups forms covalent chemical bonds between them. For example, a contact lens containing a functionalized prepolymer having hydroxyl functional groups will preferably undergo a surface modification using reactive hydrophilic SMTP containing carboxylic acid functional groups, isocyanate functional groups or epoxide functional groups: Likewise, a contact lens containing prepolymer functionalized having carboxylic acid groups will preferably undergo a surface modification using reactive hydrophilic SMTPs containing glycidyl methacrylate monomer (GMA) units to provide epoxide functional groups. The reaction of contact lenses containing functionalized fumaric and itaconic functional reactive functional groups and the reactive hydrophilic SMTP is carried out under conditions known to those skilled in the art. The functionalized, reactive, fumaric and itaconic-containing prepolymers useful in certain embodiments of the present invention can be prepared according to syntheses well known in the art and following the methods described in the following examples. The modification of the surface of the contact lens produced from one or more reactive functionalized polymeric materials containing fumaric and itaconic using one or more reactive hydrophilic SMTPs according to the present invention is still described in more detail in the examples given to continuation .

EXAMPLES Example 1: Preparation of an acid-terminated fumaric prepolymer [(diacid-F2D20)] In a 500 ml round bottom flask, carefully dried, equipped with reflux condenser, was introduced bis-,? -hydroxybutyl polydimethylsiloxane ( Mn 1624, 30.08 grams, 0.0185 moles) prepared following the procedure described in Journal of Polymer Science, Part A, 33,1773 (1995)] and fumaryl chloride (M 152.96, 6.4013 grams, , 0418 moles) (Aldrich Chemical, Milwaukee, WI). The reaction mixture was heated in an oil bath at 60 ° C. After two hours, the reaction was complete, as indicated by the loss of the CH2-OH peak at 3.5 ppm (in H-NMR). The contents of the flask (0.4 mm Hg) were dragged at 80 ° C for 2 hours. 3 mg of water and 30 ml of THF were then added to the contents. The mixture was heated to reflux until all the acid chloride groups disappeared (determined by IR 1769 cm-1). The THF was removed from the mixture by stripping in a Rotavapor. The remaining residue was then added to 200 ml of ether and extracted with 50 ml of water three times. The final residue was dried in ether with magnesium sulfate and vacuum stripped at 80 ° C for 2 hours. SEC (polystyrene standard): Mn = 2001, Mw = 3141 (Pd = 1.57) Example 2: Preparation of a prepolymer terminated in itaconate-polysiloxane acid (diacid 12D20). Into a 500 ml round bottom flask, carefully dried, equipped with reflux condenser, is introduced bis-α, β-hydroxybutyl polydimethylsiloxane (Mn 1624, 30.08 grams, 0.0185 moles) and itaconyl chloride ( Mw 166.99, 6.99 grams, 0.0418 moles). The mixture is heated in an oil bath at 60 ° C. After two hours the reaction is complete as indicated by the loss of the CH2-OH peak at 3.5 ppm (in H-NMR). The contents of the flask (<0.4 mm Hg) are vacuum entrained at 80 ° C for 2 hours. To the content are then added 3 mg of water and 30 ml of THF. The mixture is heated to reflux until all the acid chloride groups disappear (by IR 1769 cm-1). The THF is removed by dragging from the product in a Rotavapor. The remaining residue is then added to 200 ml of ether and extracted with 50 ml of water three times. The final residue in ether is dried with magnesium sulfate and then subjected to vacuum stripping at 80 ° C for 2 hours.

Example 3: Preparation of maleate-polysiloxane acid-terminated prepolymer (diacid M2D20). In a 500 ml round bottom flask, carefully dried, equipped with reflux condenser, is introduced bis-a,? -hydroxybutyl polydimethylsiloxane (Mn 1624, 30.08 grams, 0.0185 moles), 150 ml of tetrahydrofuran and aleic anhydride (Mw 98.06, 4.10 grams, 0.0418 moles). The mixture is heated in an oil bath at 60 ° C. After 16 hours, the reaction is complete as indicated by the loss of the CH2-OH peak at 3.5 ppm (in H-NMR). 5 ml of water are then added to the contents and heating is continued for 2 hours. The solution is dried with magnesium sulfate and subjected to vacuum stripping at 80 ° C for 2 hours to give the product.

Example 4: Preparation of hydrogel films from fumaric prepolymer and other comonomers A prepolymer prepared as described in Example 1, 32 parts, was mixed with 32 parts of N, N-dimethylacrylamide, 36 parts of TRIS, 27 parts. of hexanol, and 0.3 parts of Darocur® 1173 initiator (Ciba Specialty Chemical). The mixture was molded between two glass plates treated with silane and cured in an oven at 70 ° C for 1 hour. The cured films were then removed, extracted in isopropanol, boiled in water for 4 hours and then placed in borate buffered saline. The properties of hydrogel films are: water content 39%, modulus 36 g / mm2, tear strength 13 g / mm. Oxygen permeability 93 (Dk unit).

Example 5: Preparation of hydrogel film - derived from the prepolymer described in Example 1 (thermal curing) A monomer mixture was prepared from a prepolymer as described in Example 1, TRIS, DMA and initiator Vazo® 52 ( DuPont) at a weight ratio of 20/40/40/1. The mixture was then molded and processed into hydrogel films by application by application of the same procedure described in Example 4. Properties of hydrogel films: 41% water content; module 49 g / mm2; tear strength 3.0 g / mm; oxygen permeability 63 (unit Dk).

Example 6: Molding of lenses with microwave curing of variable frequency, purified with supercritical fluid, followed by direct coating. A monomer mixture consisting of a prepolymer prepared as described in Example 1, a t-butyl fumarate and polydimethylsiloxane with final cap and Mn (number average molecular weight) 1600, (F2D20), TRIS, DMA was prepared and n-hexanol at a ratio of 15/15/30/40/5. The mixture was placed between two polypropylene molds and cured under microwave conditions. After removing the molds, the lenses were removed with supercritical C02 fluid. The lenses were then placed in a distilled water solution containing a hydrophilic polymer derived from glycidyl methacrylate, N, N-dimethyl acrylamide and octafluoropentyl methacrylate (prepared as described in Example 9) and then autoclaved for 30 minutes. The lenses were then transferred to clean vials containing borate buffered saline at pH 7.1 and autoclaved. All the lenses, before and after the polymer coating treatments, were characterized in terms of water content and surface analysis (by XPS). The results are as follows. Table 2 Example 7: Preparation of hydrogel films from a prepolymer and other comonomers (UV curing) A prepolymer is mixed as described in Example 2 (30 parts) with 30 parts of N, N-dimethylacrylamide (DMA), 40 parts of 3-methacryloxypropyltris (trimethylsiloxy) silane (TRIS), 20 parts of hexanol, and 0.3 parts of Darocur 1173. The mixture is then molded between two glass plates treated with silane under UV at about 4000 microwatts for two hours. The cured films are then extracted with isopropanol overnight, followed by boiling in water and then placed in borate buffered saline at pH 7.2 to give hydrogel films.

Example 8: Synthesis of hydrophilic, reactive copolymer of N, N-dimethylacrylamide (DMA) and glycidyl methacrylate (GMA) Vazo 64 (0.0024 moles = 0.4 g) Total Moles demopomerc = 2.24 DMA-co-GMA [x = 86, y = 14]. To a 3 liter reaction flask is added N, N-dimethylacrylamide distilled (DMA, 192 g, 1.92 mol), distilled glycidyl methacrylate (GMA, 48 g, 0.32 mol) 2,2-azobisisobutyronitrile (AIBN). , "0.4 g, 0.0024 noles) and tetrahydrofuran (2000 ml) The reaction vessel is equipped with a mechanical agitator, coolant, thermal controller and nitrogen inlet tube. the solution for 15 minutes to separate the possible dissolved oxygen.The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 24 hours.The reaction mixture is then slowly added to 12 liters of ethyl ether with good agitation The reactive polymer is precipitated and recovered by vacuum filtration.The solid is placed in a vacuum oven at 30 ° C overnight to separate the ether, leaving the reactive polymer.The reactive polymer is placed in a desiccator during the storage until its use.

Example 9: Synthesis of reactive hydrophilic copolymer of N, N-dimethylacrylamide (DMA), methacrylate of 1H, 1H, 5H-octafluoropentyl (OFPMA) and glycidyl methacrylate (GMA) Pe For To a 1000 ml reaction flask were added distilled N, N-dimethylacrylamide, DMA, 64 g, 0.64 mol), 1H, 1H, 5H-octafluoropentyl methacrylate (OFPMA, 4 g, 0.012 mol, used as described). receive), distilled glycidyl methacrylate (GM, 16 g, 0.112 mol) 2,2'-azobisisobutyronitrile (AIBN, 0.12 g, 0.00072 mol) and tetrahydrofuran (1200 ml). The reaction vessel is equipped with magnetic stirrer, coolant, thermal controller and inlet tube for nitrogen. Nitrogen is bubbled through the solution for 15 minutes to remove possible dissolved oxygen. The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 20 hours. The reaction mixture is then slowly heated to 6 liters of ethyl ether with good mechanical agitation. The reactive polymer precipitates and is collected by vacuum filtration. The solid is placed in a vacuum oven at 30 ° C and left overnight to separate the ether leaving 66, 1 g of reactive polymer (79% yield). The reactive polymer is placed in a desiccator during storage until its use.

Example 10: Synthesis of hydrophilic copolymer, reactive, of N, N. dimethylacrylamide (DMA), methacrylate of 1H, 1H, 5H-octafluoropentyl (OFPMA), glycidyl methacrylate (GMA) and _ -. «%? Asmoles Molecular weight = 99.18 Molecular weight "300.15 i-opmila molecul." and HgNO 1-opnufa moleculí »CjHaFjOj Molecular weight x 142.16 Formula molecul * _-H10O3 Varo 84 (0.0001ír * .Ktt "8.T3g) Total Mole» d.monomßK "0.11a polyethylene glycol monomethyl ether methacrylate 1000 (PEGMA) To a 500 ml reaction flask is added distilled N, N-dimethylacrylamide (DMA, 8 g, 0.08 mol), methacrylate of 1H, 1H, 5H-otafluoropentyl (OFPMA) , lg, 0.003 mole, used as received), distilled diglycidyl methacrylate (GM, 4g, 0.028 mole), polyethylene glycol monomethyl ether methacrylate 1000 (PEGMA, 8 g, 0.007 mole), 2,2 * -azobisisobutyronitrile ( AIBN, 0.03 g, 0.00018 mol) and tetrahydrofuran (300 ml). The reaction vessel is equipped with magnetic stirrer, coolant, thermal controller and nitrogen inlet. Nitrogen is bubbled through the solution for 15 minutes to remove possible dissolved oxygen. The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 72 hours. The flash evaporation of the solvent followed by lyophilization leaves the reactive polymer, a semi-solid type wax.

Example 11: Synthesis of reactive hydrophilic copolymer N-vinyl-2-pyrrolidinone (NVP) and 4-vinylcyclohexyl-l, 2-epoxide (VCHE) Molecular weight = 124.18 To a 1-liter reaction flask is added N-vinyl-2-pyrrolidinone (NVP, 53.79 g, 0.48 mol), 4-vinylcyclohexyl-1,2-epoxide (VCHE, 0.10.43 g, 0.084). moles), 2,2'-azobisisobutyronitrile (AIBN, 0.05 g, 0.0003 mol) and THF (600 ml). The reaction vessel is equipped with magnetic stirrer, coolant, thermal controller and inlet tube for nitrogen. Nitrogen is bubbled through the solution for 15 minutes to separate the possible oxygen ... dissolved. The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 20 hours. The reaction mixture is then slowly added to 6 liters of ethyl ether with good mechanical agitation. The copolymer precipitates and is recovered by vacuum filtration. The solid is placed in a vacuum oven at 30 ° C overnight to separate the ether leaving the reactive polymer. The reactive polymer is placed in a desiccator during storage until its use.

Example 12: Synthesis of a reactive hydrophilic copolymer of N, -dimethylacrylamide (DMA), lauryl methacrylate (LMA) and glycidyl methacrylate (GMA). 1000 ml of distilled N, N-dimethylacrylamide (DMA, 32 g, 0.32 mole), lauryl methacrylate (LMA, 1.5 g, 0.006 mole, used as received), methacrylate are introduced into a 1000 ml reaction flask. distilled glycidyl (GM, 8 g, 0.056 mol) 2, 2'-azobisisobutyronitrile (AIBN, 0.06 g, 0.00036 mol) and tetrahydrofuran (600 ml). The reaction vessel is equipped with a magnetic stirrer, coolant, thermal controller and inlet pipe for nitrogen. Nitrogen is bubbled through the solution for 15 minutes to remove possible dissolved oxygen. The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 20 hours. The reaction mixture is slowly added to 3 liters of ethyl ether with good mechanical agitation. The reactive polymer precipitates and is collected by vacuum filtration. The solid is placed in a vacuum oven at 30 ° C overnight to separate the ether, leaving the reactive polymer. The reactive polymer is placed in a desiccator during storage until its use.

Example 13: Synthesis of reactive hydrophilic copolymer of N, N-dimethylacrylamide (DMA) and methacrylic acid (MAA) Molecular weight = (99.13) mon Molecular formula = Molecular weight = [86.09] mon irU4.Nr _._ T.nn Molecular formula * [C_H "0,] mon AIBN (0.0016 moles «0.24 g) Total Moles of 1.56 2-orouanol anhydrous 2000 ml To a 3000 ml reaction flask are added distilled NN-dimethylacrylamide (DMA, 128 g, 1.28 mol), methacrylic acid (MAA, 32 g, 0.37 mol) 2,2'-azobisisobutyronitrile (AIBN, 0, 24 g, 0.0016 mol) and anhydrous 2-propanol (2000 ml). The reaction vessel is equipped with a magnetic stirrer, coolant, thermal controller and nitrogen inlet. Nitrogen is bubbled through the solution for 15 minutes to remove any dissolved oxygen. The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 72 hours. The volume of the reaction mixture is halved by flash evaporation. The reactive polymer is precipitated in 8 liters of ethyl ether and then collected by vacuum filtration. The solid is placed in a vacuum oven at 30 ° C overnight to separate the ether leaving the reactive polymer. The reactive polymer is placed in a desiccator for storage until its use.

Example 14: Synthesis of a hydrophilic reactive polymer of N, -dimethylacrylamide (DMA) and 12-methacryloyloxydecanoic acid (LMAA) Molecular weight »99.13 Molecular weight = 284.40 F Foorrmmuullaa mmoolleeccuullaarr _ a__ CsHaNO Molecular formula = C1ßHM04 1.5.28, 0.153 moles 4.8 fl, 0.017 moles Tola! moles demonomeip = 0.17 THF Vazo 64 (O.0D02 motes »0.032g) To a 500 ml reaction flask is added distilled N, N-dimethylacrylamide (DMA, 15.2 g, 0.153 mole), 12-methacryloyloxydecanoic acid (LMAA, 4.8 g, 0.017 mole), 2,2'-azobisisobutyronitrile ( AIBN, 0.032 g, 0.0002 mole) and anhydrous tetrahydrofuran (200 ml). The reaction vessel is equipped with magnetic stirrer, coolant, thermal controller and inlet tube for nitrogen. Nitrogen is bubbled through the solution for 15 minutes to separate the possible oxygen. The reaction flask is then heated at 60 ° C under an inert atmosphere of nitrogen for 72 hours. The reaction mixture is then slowly added to 2.5 liters of heptane with good mechanical agitation. The reactive polymer precipitates and is collected by vacuum filtration. The solid is placed in a vacuum oven at 30 ° C overnight at 30 ° C to separate the ether leaving the reactive polymer. The reactive polymer is placed in a desiccator during storage until its use. Contact lenses made using the unique materials of the present invention are used as is customary in the field of ophthalmology. Although certain specific structures and compositions of the present invention have been presented and described here, it will be clear to those skilled in the art that various modifications can be made without departing from the spirit and scope of the concept on which the invention is based and that it does not. it is limited to the particular structures shown here and described except as indicated by the frame of the appended claims.

Claims (27)

R e i v i n d i c a c i o n s

1 . A prepolymer selected from the group consisting of functionalized compounds having the following formula: YCO-CH = CHCO (Ri) n (SiR2R30) m (SiR2R3) (Rx) nWOCCH = CH-COY Y CH2 = C (CH2COY) COW (Ri) n (SiR2R30) m (SiR2R3) (Rx) nWOC (CH2COY) C = CH2 where Ri is selected from the group consisting of alkyl and alkylen containing ether linkages, R2 and R3 are independently selected from the group consisting of alkyl groups, phenyl groups, alkyl groups substituted with halogen, phenyl groups substituted with halogen, alkyl groups containing ether linkages and phenyl groups containing ether linkages, is O or NH, n is an integer between 1 and 10, is an integer between 2 and 200, and Y is a radical having a reactive functional group selected from the group consisting of in hydroxyl, carboxyl, oxazolone, epoxy and anhydride functional groups provided that when W is O, Y is not a diethanolamine radical.

2. The prepolymer according to claim 1 wherein Rx contains 1-10 carbon atoms.

3. The prepolymer according to claim 1 wherein the functionalized compound has the following formula: YCO-CH = CHCO (R?) "(SiR2R30) m (SiR2R3) (Ra)" WOCCH = CH-COY where Ri "is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 200, W is O and Y is OH and is in the configuration trans

4. The prepolymer according to claim 1 wherein the functionalized compound has the following formula: CH2 = C (CH2COY) CO (R1) n (SiR2R30) Ir? (SiR2R3) (Rx) nWOC (CH2COY) C = CH2 where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, is O and Y is OH.

5. The prepolymer according to claim 1 wherein the functionalized compound has the following formula: YCO-CH = CHCOW (R1) n (SiR2R30) m (SiR2R3) (Rx) nWOCCH = CH-COY where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 200, is O and Y is OH and is in the cis configuration.

6. A copolymer prepared by polymerizing a monomer mixture comprising (A) 20 to 80% by weight of at least one prepolymer selected from the group consisting of compounds having the following formula: YCO-CH = CHCOW (Ri) n (SiR2R ^ O) m (SiR2R3) (Ri) nWOCCH = CH-COY and CH2 = C (CH2COY) COW (R1) n (SiR2R30) m (SiR2R3) (Ra) n OC (CH2COY) C = CH2 where Ri is selected from the group consisting of alkyl and alkylen containing ether linkages, R2 and R3 are independently selected from the group consisting of alkyl groups, phenyl groups, alkyl groups substituted with halogen, phenyl groups substituted with halogen, alkyl groups containing ether linkages and phenyl groups containing ether linkages, W is 0 or NH, n is an integer between 1 and 10, m is an integer between 2 and 200, and Y is a radical having a reactive functional group selected from the group which consists of hydroxyl, carboxyl, oxazolone, epoxy and anhydride functional groups provided that when W is O, Y is not a diethanolamine radical, and (B) 5 to 50 weight percent of at least one copolymerizable monomer forming the device .

7. The copolymer according to claim 6 wherein the monomer mixture comprises: 10 to 50% by weight of at least one additional monomer containing silicone and 10 to 50% by weight of at least one copolymerizable hydrophilic monomer forming the device.

8. The copolymer according to claim 6 wherein the component (A) has the following formula: YC0-CH = CHC0W (Ri) n (SiR2R30) m (SiR2R3) (R2) n OCCH = CH-COY where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer 'between 5 and 200, is O and Y is OH and is in the trans configuration .

9. The copolymer according to claim 6 wherein the component (A) has the following formula: CH2 = C (CH2COY) CO (Ri) n (SiR2R30) m (SiR2R3) (Rx) n OC (CH2COY) C = CH2 where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 200, W is 0 and Y is OH.

10. The copolymer according to claim 6 wherein the component (A) has the following formula: YCO-CH = CHCOW (Ri) n (SiR2R30) m (SiR2R3) (Ri) nWOCCH = CH-COY where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH and is in cis configuration .

11. The copolymer according to claim 7 wherein the component (A) has the following formula: YCO-CH = CHCOW (Ri) n (SiR2R30) m (SiR2R3) (Ri) nWOCCH = CH-COY where Ri is selected from the group consisting of alkyl and alkyne containing ether bonds, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, is O and Y is OH and is in the trans configuration.

12. The copolymer according to claim 7 wherein the component (A) has the following formula: CH2 = C (CH2COY) COW (R?) N (SiR2R30) m (SiR2R3) (Ri) r_WOC (CH2COY) C = CH2 where Ri is selected from the group consisting of alkyl and alkylen containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH.

13. The copolymer according to claim 7 wherein the component (A) has the following formula: YCO-CH = CHCO (Ri) n (SiR2R30) m (SiR2R3) (Rj.) NWOCCH = CH-COY where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH and is in cis configuration

14. A medical device comprising a copolymer prepared by polymerizing a mixture of monomers comprising, as major components, (A) 20 to 80 weight percent of at least one prepolymer selected from the group consisting of compounds of the following formula: YCO-CH = CHCOW (R1) "(SiR2R30) m (SiR2R3) (Ri) nWOCCH = CH-COY and CH2 = C (CH2COY) COW (Ri) n (SiR2R30) m (SiR2R3) (Rj.) N OC ( CH2COY) C = CH2 where Ri is selected from the group consisting of alkyl and alkylen containing ether linkages, R2 and R3 are independently selected from the group consisting of alkyl groups, phenyl groups, alkyl groups substituted with halogen, phenyl groups substituted with halogen, alkyl groups containing ether linkages and phenyl groups containing ether linkages, is O or NH, n is an integer between 1 and 10, m is an integer between 2 and 200, and Y is a radical having a reactive functional group selected from the group it consists of hydroxyl, carboxyl, oxazolone, epoxy and anhydride functional groups provided that when it is O, Y is not a diethanolamine radical, and (B) 5 to 50 weight percent of at least one copolymerizable monomer forming the device.

15. The medical device according to claim 14 wherein the monomer mixture comprises: 10 to 50 weight percent of at least one additional hydrophilic monomer containing silicone and 10 to 50 weight percent of at least one hydrophilic monomer capable of completing the device .

16. The medical device according to claim 14 wherein the component (A) has the following formula: YCO-CH = CHCOW (Ri) n (SiR2R30) m (SiR2R3) (Ra) nWOCCH = CH-COY where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH and is in the trans configuration .

17. The medical device according to claim 14 wherein the component (A) has the following formula: CH2 = C (CH2COY) COW (Rj.) N (SiR2R30) m (SiR2R3) (Rx) nWOC (CH2COY) C = CH2 where Ri is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, is O and Y is OH.

18. The medical device according to claim 14 wherein the component (A) has the following formula: YCO-CH = CHCOW (Ra) n (SiR2R30) m (SIR2R3) (Rx) n OCCH = CH-COY where Ra is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH and is in the cis configuration .

19. The medical device according to claim 15 wherein the component (A) has the following formula: YCO-CH = CHCOW (R?) N (SIR2R30) m (SiR2R3) (Ra) nWOCCH = CH ~ COY where Ra is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, is O and Y is OH and is in the trans configuration.

20. The medical device according to claim 15 wherein the component (A) has the following formula: CH2 = C (CH2COY) COW (R1) n (SiR2R30) m (SiR2R3) (Rx) nWOC (CH2COY) C = CH2 where R is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH.

21. The medical device according to claim 15 wherein the component (A) has the following formula: YCO-CH = CHCO (R1) n (SiR2R30) m (SiR2R3) (Ra) nWOCCH = CH-COY where Ra is selected from the group consisting of alkyols and alkyols containing ether linkages, R2 and R3 are methyl, n is 3 or 4, m is an integer between 5 and 100, W is O and Y is OH and is in the cis configuration .

22. The medical device according to claim 14 wherein the medical device is selected from the group consisting of heart valves, infraocular lenses, contact lenses, intrauterine devices, vessel substitutes, artificial ureters and artificial breast tissue.

23. The medical device according to claim 22, wherein the medical device is a contact lens.

24. The medical device according to claim 23, wherein the medical device is a soft ophthalmic lens.

25. The medical device according to claim 15 wherein the medical device is selected from the group consisting of heart valves, infraocular lenses, contact lenses, intrauterine devices, vessel substitutes, artificial ureters and artificial breast tissues.

26. The medical device according to claim 25 wherein the medical device is a contact lens.

27. The medical device according to claim 26 wherein the medical device is a soft contact lens.