Classifications

• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
  • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
  • G02B1/041—Lenses
  • G02B1/043—Contact lenses

Definitions

• Soft contact lenses are particularly subject to attack. 7
• the need for careful handling of contact lenses generally, and regular sterilization of soft contact lenses has presented a long-standing problem in the art. 2-9 Serious and intensive efforts have been made to solve this problem. The most extensive effort has related to a lens identified as the
• ASEPTOPLAST (trademark) lens. 3-6 Germicidal agents, hexachlorophene and a commercial germicide, COROBEX CP-4 (trademark) consisting of 0.3% boric acid, 2.25% phenylmercuric borate, 0.11% 2-ethyl-hexanol, and
• the ASEPTOPLAST lens approach although a significant effort to solve a very serious and long-standing problem, is limited by the very serious risk that leaching of the asepticizing agents from the lens polymer will not only decrease the biostatic action of the lens but, more importantly, may irritate or seriously damage the eye of the user.
• the polymers which are suitable for preparation of contact lenses as modified according to this invention are known lens polymers, and the monomer and polymer systems and methods of handling these systems are prior art.
• Many examples of lens polymers and monomers used for polymerization and copolymerization to produce lens polymers are described herein and in the references cited at the end of this specification, which are incorporated herein as fully as though set forth for disclosure of the monomers, polymers and copolymers and processing methods disclosed therein.
• Asepticizing agents inherently containing or modified by. reaction to include a reactive group caoable of polymerization, e.g., groups referred to here as a "polymerizable, vinyl” group, i.e., one which is polymerized with, lens monomers also including a polymerizable vinyl group to bond the aseptic agent to the backbone of the polymer.
• a reactive group caoable of polymerization e.g., groups referred to here as a "polymerizable, vinyl” group, i.e., one which is polymerized with, lens monomers also including a polymerizable vinyl group to bond the aseptic agent to the backbone of the polymer.
• an asepticizing agent is bonded to the polymer by reaction of a reactive group on the asepticizing agent with a reactive group on the already polymerized polymer.
• benzyltrialkyl ammonium halide e.g., benzyl trimethyl ammonium chloride
• p-vinyl-benzyl trimethyl ammonium chloride e.g., methyl methacrylate and ethylene glycol dimethacrylates and soft lenses, e.g., hydroxyethyl methacrylate and triethylene glycol dimethacrylate polymers, as well as many modifications of these basic polymer systems.
• asepticizing agents which can be applied within this broad inventive concept, namely hydroxyl substituted benzene compounds, e.g., phenols, resorcinols and catechols, are more specifically disclosed in my aforesaid co-pending application Serial No. 920,670, filed June 30, 1978. Additional examples of the inventive concept as applied to a variety of polymers and a variety of asepticizing agents are disclosed herein.
• the invention contemplates contact lens polymers generally, without respect to the particular polymer or copolymer matrix, to which asepticizing agents are chemically bonded, without respect to the nature of the particular asepticizing agent.
• a preferred form of the invention contemplates bonding polymerizable vinyl group containing asepticizing agents into the backbone of polymers and copolymers formed by polymerizing polymerizable vinyl group containing lens monomers.
• Another preferred form of the invention contemplates the bonding, through any pair of reactive groups, of an asepticizing group to an already formed polymer.
• the present invention contemplates alternative routes to forming lens polymers and lenses in which the asepticizing agent is bonded to the polymer. Depending upon the nature of the asepticizing agent and the polymer, one particular approach may, in different circumstances, be preferred. Bonding Through a Polymerizable Vinyl Group
• Monomers for polymerization or copolymerization of contact lens polymers by the polymerization of polymerizable vinyl groups are very well known and generally, are suitable for use in this invention.
• the principles of this invention are most valuably utilized in connection with hydrogel lenses. Hydrogels, and their application to lenses have been disclosed by Wichterle et al, along with many variations of this class of materials, in a series of patents issuing over the past. nearly two decades. 33,38,42-43,46-47,
• Suitable hydrogel polymer systems include the polymerization products of polyethylene glycol methacrylate and polyethylene glycol dimethacrylates; triethylene glycol methacrylate, methyl methacrylate and triethylene glycol dimethacrylate; dimethyl amino ethyl methacrylate and triethanol amine dimethacrylate.
• hydrogels formed by the polymerization of esters of acrylic and methacrylic acid with alcohols having hydrophili ⁇ groups which after polymerization impart hydrophilic properties to the polymer.
• Wichterle et al disclose a number of acrylic and methacrylic acids, alcohols and cross-linking agents suitable for use in preparing hydrogels of this class. 38
• Starting materials for producing these hydrogels include the esters of acrylic and methacrylic acid with alcohols having hydrophilic groups which after polymerization impart hydrophilic properties to the polymer obtained.
• a major portion of a monoester of acrylic or methacrylic acid with a bifunctional alcohol which has an esterifiable hydroxyl group and at least one additional hydrophilic functional group is co-polymerized with a small amount of a diester of these acids and of an alcohol which has at least two esterifiable hydroxyl groups until a shape retaining body is obtained.
• the polyfunctional alcohols forming one of the constituent elements of the aforementioned monoester, and preferably also the alcohol constituent of the diester may have additional hydrophilic groups in their molecule which make the esters water soluble even after two or more of the hydroxyl groups are esterified by the acrylic or methacrylic acid.
• the corresponding acrylates may be substituted for the methacrylates.
• diesters mentioned above may be replaced by other cross-linking agents such as triethanolamine dimethacrylate, triethanolamine trimethacrylate, tartaric acid dimethacrylate, triethylene glycol dimethacrylate, the dimethacrylate of bis-hydroxyethylacetamide.
• This general class of polymers has been used to prepare substantially anhydrous sparingly cross-linked hydrophilic polymers capable of being swollen when placed in water which consists of a high percentage, e.g., 98% or more, of a monoester of acrylic or methacrylic acid and an alcohol having an esterifiable hydroxyl group and at least one additional hydroxyl group and less than 2% of a cross-linking agent of a diester of the alcohol.
• Hydrogel lens polymers having selected properties and advantages which are suitable for use in this invention have been developed by a number of workers.
• Seiderman 48 discloses one such formulation. These polymers result from polymerization of hydroxyalkyl acrylate and methacrylate esters in copolymeric composition with minor amounts of a longer chain alkyl acrylate or methacrylate ester comonomer and a cross-linking comonomer such as allyl diglycol carbonate, glycol diacrylates, glycol dimethacrylates, polyglycol diacrylates and dimethacrylates, allyl methacrylates, triallyl cyanurate, divinylbenzene, and trivinylcyclohexane.
• a cross-linking comonomer such as allyl diglycol carbonate, glycol diacrylates, glycol dimethacrylates, polyglycol diacrylates and dimethacrylates, allyl methacrylates, triallyl cyanurate, divinyl
• hydroxyalkyl methacrylates examples include: 2-hydroxyethyl methacrylates, 2-hydroxypropyl methacrylate, and the like. Other hydroxyalkyl methacrylates can be used with varying degrees of satisfaction. Also, alkylamino alkyl methacrylates, such as 2-dimethylaminoethyl methacrylate, 2-butylaminoethyl methacrylate, dimethylaminopropyl methacrylamide, quaternary salts of the same and the like, can be used. Examples of suitable alkyl methacrylates are: methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate and the like.
• Suitable longer chain alkyl methacrylates are: lauryl methacrylate, or other alkyl methacrylates wherein the alkyl radical thereof contains from out 5 to about 20 carbon atoms in the alkyl chain, such as capryl, palmityl, stearyl, cyclohexyl methacrylates, and alkyl cyclohexyl, and cyclo-octyl and cyclo-dodecyl methacrylates.
• Suitable cross-linking agents are: olefin glycol dimethacrylates such as : ethylene glycol dimethacrylate, diethylene glycol dimethacrylates, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1, 4-butylene glycol dimethacrylate and 1,3-butylene glycol dimethacrylate.
• suitable catalysts are: benzoyl peroxide, chlorobenzoyl peroxide, lauryl peroxide, tertiary butyl peroxycarbonate, isopropyl peroctoate, etc.
• Modified polyvinylpyrrolidone resins in which a mixture of polyvinyl pyrrolidone, vinyl pyrrolidone, a hydroxyalkyl methacrylate and a cross-linking agent are reacted 53 may also be reacted with polymerizable vinyl group containing asepticizing agents according to the principals of this invention.
• Polymerizable vinyl group containing aseptic agents may, according to this invention, be polymerically bonded into hydrogels modified by the inclusion of glycidyl methacrylate, glycidyl acrylate and glycidyl crotonate 60 , hard plaasstic hydrogels including triethylene glycol dimethacrylate 65 soft hydrophilic lenses modified by the inclusion of trimethylolpropane trimethacrylate, hydrogel copolymers of dihydroxyl alkyl acrylates and methacrylates copolymerized with alkyl acrylates and methacrylates, soft contact lenses made of a copolymer derived from a monomer mixture of hydroxyethyl or hydroxypropyl acrylates and methacrylates with 4 to 13 carbon hydroxyalkyl acrylates and methacrylates, 75 soft lenses prepared from copolymers modified by the inclusion of polyalkylene glycol acrylates and methacrylates, 76 hydrophilic polymers from polymerization of diester-free
• aseptic agents which include a polymerizable vinyl group with styrene modified acrylate and methacrylate polymers as disclosed in my co-pending application Serial No. 920,670, with vinyl pyrrolidone modified hydroxy alkyl acrylate hydrogels, with alkyl ether acrylates and methacrylates with vinyl silane and with substituted alkyl and hydroxyalkyl acrylate and methacrylate monomers, all as disclosed in my copending application Serial No. 979,295, with methyl methacrylate modified hydroxy ethyl methacrylate lenses as disclosed in my copending application Serial No. 930,665 with the known acrylic and methacrylic lens polymers and modifications of acrylic and methacrylic lens polymers.
• vinyl lens polymers include any polymer or copolymer resulting from the polymerization of reactive vinyl groups.
• Vinyl compounds which may be used, as either major or minor constituents, in lens polymers of the class with which this invention may be used include the following compounds which include a polymerizable vinyl group having the general structure: and homalogous allyl and crotyl compounds, wherein R 1 is selected from a group consisting of: (1) -Cl ; ( 2 ) -F; ( 3) -Br; ( 4) lower , 1-4 carbon , alkyl , halogen, amine and hydroxy substituted lower alkyl; (5) lower, 1-4 carbon, alkoxy, halogen, amine and hydroxy substituted alkoxy; (6) lower, 6-9 carbon, aralkyl and phenyl substituted aralkyl, i.e..
• s is -H or a single or double substituent, alike or different, on the phenyl ring, said substituent being selected from the group consisting of -Cl, -F, -OH, -NH 2 , -NO 2 , -SO 4 , -CH and -OCH 3 ; (7) wherein R 2 and R 3 are selected from the group consisting of -H, lower alkyl, 6-9 carbon
• R i through R v is selected from the group consisting of
• R 1 always being selected to permit polymerization or copolymerization of the vinyl group monomer, vinylidene monomers,
• R 1 and R 4 are as defined with respect to R 1 above are also suitable candidate monomers for use in this invention.
• Acrylates, and methacrylates especially, are particularly interesting monomers for use in this invention.
• Such compounds are generally of the formula:
• R 5 or R 6 are selected from the group consisting of -H; -CH 3 ; -C 2 H 5 and
• R 7 is selected from the group consisting of (1) -OH; (2) O-R 8 , wherein R 8 is 1 to
• R 2 and R 3 being as defined above; (4) -NCO; or (5) -CN.
• R- and R are as defined above , -NO 2 and -SO 4 .
• Acrylamides such as dimethylaminoethyl acrylamides, dimethylaminopropyl acrylamide and analogs of the above, are suitable for use in this invention.
• Suitable methacrylamides include dimethylaminopropyl methacrylamide, dimethylaminoethyl methacrylamide, and the diethylamino and methylethylamino analogs of the above.
• Difunctional methacrylamides are also contemplated, e.g., aminoethylaminoethyl dimethacrylamide, aminopropylaminoethyl dimethacrylamide, etc., and aminopropyIpiperazinepropyl dimethacrylamide.
• silicone monomer systems include polymerizable vinyl group monomers, for example
• Such monomers may be a minor part of the total monomer system, but provide reactive sites for bonding polymerizable vinyl group containing asepticizing agents into the polymer to prevent any leaching of the asepticizing agent.
• Di-vinyl functional monomers of this class serve as cross-linking agents.
• this invention is applicable to the POLYCON (Trademark) type lens in which both acrylate and silicone polymerization may occur.
• Asepticizing agents generally, i.e., bactericides, fungicides, viricides, anti-rickettsiae agent, to which a polymerizable group is attached or can be attached directly or indirectly, may be used within the principle of this invention, irrespective of the particular nature of the asepticizing agent, so long as the asepticizing agent does not interfere with the polymerization process or destroy the optical properties of the lens polymer.
• asepticizing agents bound as described in this invention will be less irritating and more compatible with body fluids and tissues than the unbonded asepticizing agents would be.
• the asepticizing agents should be effective within the general pH range of about 6.5 to about 8.5. Since differing asepticizing agents exhibit biocidal or biostatic (inhibiting growth of microorganisms) effectiveness at differing concentration levels, only general guidelines for the amount of asepticizing agents which should be polymerized into the lens polymer can be given.
• asepticizing agent concentration will range from about 0.001 to 10%, by weight, of the lens polymer and, most commonly, will fall within the 0.1 to 3% weight concentration range.
• the same concentration of asepticizing agent which is effective as a biocide in solution will also be effective as a biostatic asepticizing agent in the same concentration in the lens. Since the asepticizing agents tend to be less irritating when bonded to the polymer, however, it is possible for the concentration of asepticizing agent in the polymer to be increased, e.g., to from 3 to 10 times the optimally effective biocidal concentration of the asepticizing agent in the unbonded form in solution. Ultimately, the optimum biologically effective concentration of asepticizing agent in the polymer must be determined through established biological screening techniques, which are well established in clinical and developmental work.
• asepticizing agents having bacteriacidal and bacteriastatic effects which are suitable for use within the principals of this invention are chlorobutanol, hexachlorophene, chlorophenesin, benzylkonium compounds generally, sulfa derivatives, organo-mercurial compounds, hydroxyquinolin, substituted phenols generally, and analogs of these classes of compounds.
• Trichlorotertiary butyl alcohol exemplifies a class of compounds which are suitable for use in lenses according to the invention; indeed, the present invention makes possible the use of this compound and analogs thereof as an asepticizing agent in connection with eye tissue notwithstanding that this class of compounds cannot be used alone without undue irritation to many users.
• trichlorobutanol could not be used as an asepticizing agent for hydrogel soft contact lenses or as a preservative in hydrogel soft contact lens solutions because it concentrates in the hydrogel and leaches into the tear fluid irritating and damaging eye tissue.
• these compounds retain their physiological activity but are non-irritating or substantially less irritating to eye tissue than the compounds used alone.
• n is a positive integer of from 1 to 10.
• spacer methyl, or other, groups of from 1 to 3 or 4 such groups are quite satisfactory, although spacer methyl groups up to 10 carbon atoms may conveniently be used. There is no reason why high molecular weight spacer moieties could not be used, within the limits of steric hindrance, but there is no apparent advantage in greater spacing.
• Chlorobutanol may also be reacted with glycidyl methacrylate to produce the following polymerizable vinyl group containing compounds which is suitable for use in this invention:
• Benzylkonium compounds which may be both bacteriastatic and fungastatic asepticizing agents, may also be modified to include a polymerizable vinyl group for use in accordance with this invention.
• benzylkonium compounds could not be used in hydrogel soft lens because they concentrate in the hydrogel and leach into the eye and may cause severe tissue damage. This difficulty may be overcome by polymerizing the benzylkonium to the lens polymer to thereby bond the benzylkonium group to the polymer and prevent leaching with consequent irritation or damage to the eye.
• Exemplary of such benzylkonium compounds include:
• R 1 and R 2 are alkyl groups having from 1 to 18 carbon atoms, and most commonly is methyl, and n is a positive integer of from 1 to 18.
• R 1 and R 2 are alkyl groups having from 1 to 18 carbon atoms, and most commonly is methyl, and n is a positive integer of from 1 to 18.
• R 1 and R 2 are alkyl groups having from 1 to 18 carbon atoms, and most commonly is methyl, and n is a positive integer from 1 to 18.
• R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• n is a positive integer from 1 to 10 and R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• n is a positive integer from 1 to 10 and R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• n is a positive integer of from 1 to 2000 and R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• n is a positive integer of from 1 to 2000 and R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• n is a positive integer from 1 to 10 and R 1 , R 2 and R 3 are 1 to 18 carbon alkyl and, preferably, where two of R 1 , R 2 and R 3 are methyl and one of R 1 , R 2 and R 3 is a 8 to 18 carbon alkyl.
• Substituted phenols are suitable antibacterial asepticizing agents, exemplary of which are:
• R 1 , R 2 , R 3 , R 4 and R 5 are halide, hydrogen, or 1 to 9 alkyl or alkoxy, at least one of R 1 through R 5 being halide, and R 6 is hydrogen or methyl.
• R 1 , R 2 , R 3 , R 4 and R 5 are halide, hydrogen, or 1 to 9 alkyl or alkoxy, at least one of R 1 through R 5 being halide, and R 6 is hydrogen or methyl.
• R 1 , R 2 , R 3 , and R 4 and R 5 are halide, hydrogen, or 1 to 9 alkyl or alkoxy, at least one of R 1 through R 5 being halide, and R 6 is hydrogen or methyl.
• R 1 , R 2 , R 3 , R 4 and R 5 are halide, hydrogen, or 1 to 9 alkyl or alkoxy, at least one of R 1 through R 5 being halide, and R 6 is hydrogen or methyl and n is zero or a positive integer of from 1 to 10.
• R 1 , R 2 , R 3 , R 4 and R 5 are halide, hydrogen, or 1 : to 9 alkyl or alkoxy, at least one of R 1 through R 5 being halide, and R 6 is hydrogen or methyl and n is zero or a positive integer of from 1 to 10.
• R 1 , R 2 , R 3 , R 4 and R 5 are halide, hydrogen, or 1 to 9 alkyl or alkoxy, at least one of R 1 through R 5 being halide, and R 6 is hydrogen or methyl and n is zero or a positive integer of from 1 to 10.
• microbiological activity of two classes of biocidal asepticizing agents can be imparted to contact lenses by polymerizing with the lens polymer asepticizing agents having different or plural biocidal characteristics.
• the lens forming monomer can be copolymerized with polymerizable vinyl group containing quaternary ammonium compounds and vinyl group containing chlorphenesin compounds.
• polymerizable vinyl group containing quaternary ammonium compounds and vinyl group containing chlorphenesin compounds These two classes of compounds are selected merely to exemplify the concept of including two asepticizing agents in a single lens forming polymer.
• Two biologically active agents can also be combined into one monomer containing a polymerizable vinyl group.
• a chlorphenesin-quaternary ammonium polymerizable vinyl group monomer can be prepared and copolymerized with the lens polymer.
• Merely exemplary of this approach to building non-leachable asepticizing agents into lens polymers are the following compounds which contain polymerizable vinyl group and the two classes of asepticizing agents referred to:
• R 1 , R 2 , R 3 , R 4 and R 5 is a halogen and remainder is hydrogen, hydroxy, halogen, or lower 1 to 10 carbon alkyl.
• Hexachlorophene a recognized bactericide
• Examples of polymerizable analogs of hexachlorophene include:
• n is a positive integer from 1 to about 18, m is zero or a positive integer from 1 to about 18, R 1 through R 8 are halogen or lower , 1 to 10 carbon , alkyl or alkoxy , at least one of R 1 to R 3 , and at least one of R 5 to R 8 being halogen, the vinyl containing substituent in the next preceding two structures being attached to either phenyl ring at the ortho, meta or para positions with respect to the hydroxy groups, R 9 being hydrogen, halogen or 1 to 4 carbon alkyl.
• Biocidally effective halogen substituted phenyl compounds generally are satisfactory condidates for utilization in this invention. These classes of compounds would include the following:
• R 1 through R 5 is halogen and each of R 1 through R 5 are halogen, hydroxy, hydrogen or lower 1 to 10 carbon, alkyl or alkoxy, and R 6 is hydrogen, haloge or 1 to 4 carbon alkyl, e.g., pentachlorophenyl methacrylate,
• R 1 to R 5 and of R 6 to R 10 is halogen and each of R 1 to R 10 is hydrogen, hydroxy, halogen or lower, 1 to 10 carbon, alkyl or alkoxy; and vinyl, allyl, and crotonyl and glycidyl ethers, e.g.,
• R 1 to R 5 is halogen, and each of R 1 to R 5 is hydrogen, hydroxy, halogen or lower 1 to 10 carbon alkyl or alkoxy.
• biocidal asepticizing agents which can be used in accordance with this invention include: Quinolinol derivatives, to which a polymerizable group has been attached:
• R, to R. is hydroxyl
• each of R 1 to R 4 is hydrogen, hydroxy, halogen or lower, 1 to 10 carbon, alkyl or alkoxy
• R 1 to R 4 is vinyl group containing substituent, at least one of R 1 to R 4 is hydroxyl and the remaining R 1 to R 4 positions are hydrogen, hydroxy, halogen or 1 to 4 carbon alkyl.
• Organo-mercury compounds which have been modified clude a polymerizable vinyl group: wherein R 1 is halogen, hydrogen or 1 to 4 carbon alkyl, and n is zero or a positive integer of 1 to 10, and polymerizable vinyl group containing thio-mercury compounds, e.g..
• X is a protonic acid group, or salt thereof, selected from the group consisting of:
• Y is a polymerizable vinyl group containing substituent selected from the group consisting of
• n zero or a positive integer of 1 to 10
• R 1 being hydrogen, halogen, or 1 to 4 carbon alkyl.
• R 1 and R 2 are polymerizable vinyl group containing substituent selected from the group consisting of:
• R 3 being hydrogen, halogen or 1 to 4 carbon alkyl, and n being zero or a positive integer of 1 to 10.
• Polyvinyl amine-vinyl sulfonate sodium salt copolymers as described by Dawson et al 13 may be converted to substituted sulfanilamides, and then graft polymerized with acrylic monomers as described by Smets et al 90 .
• a water-soluble sulfanilamide containing polymer may be polymer bound into a hydrogel lens polymer to provide antibacterial properties.
• anti-fungal, anti-viral, anti-rickettsial cind enzyme inhibitory properties may also be incorporated.
• CAPTAN® and its analogs may be used to produce a polymer network with a fungistatic agent bound to the polymer backbone.
• asepticizing monomers include:
• R 1 is a polymerizable vinyl group containing substituent selected from the group consisting of:
• R 2 being hydrogen, halogen or 1 to 4 carbon alkyl, and n being zero or a positive integer of 1 to 10.
• Quaternary ammonium - polymerizable vinyl derivatives of CAPTAN ® e.g.:
• n is zero or a positive integer of 1 to 10.
• Salicylanilide derivatives which include a polymerizable vinyl group, e.g.,:
• R 1 or R 3 is a polymerizable vinyl group containing substituent selected from the group consisting of:
• R 5 being hydrogen, halogen or 1 to 4 carbon alkyl, n being zero or a positive integer of 1 to 10, one of R 1 to R 4 is hydroxyl, the remainder of R 1 to R 4 being hydrogen, hydroxyl, halogen or 1 to 7 carbon alkyl or alkoxy.
• Adamantine derivatives such as adamantaryl methacrylate, adamantaneamine-glycidyl methacrylate adduct, adamantane carboxylic acid chloride, allyl adamantaneamine hydrochloride and methacryloxyethyl adamantane carboxylate add viricidal activity to lenses
• Suitable enzyme inhibibors are the bioflavonoids quercetin and rutin modified with polymerizable vinyl groups in the form of alkenyl ethers or esters, and then copolymerized with acrylic monomers to give a polymer bound enzyme inhibitor to prevent enzyme attack of hydrogel contact lenses; for example:
• Antirickettisial effectiveness is built into lens polymers by copolymerization of analogous derivatives of chloroamphenicol.
• Lens blanks are prepared by mixing monomers and asepticizing agent conventionally and placing the mixture in an oven to begin the polymerization. Polymerization is carried out conventionally between 40°C and 100 °C. Blanks are then annealed for several hours at 85°C, and lenses are cut and polished. In the case of soft lenses, the polished lenses are hydrated in saline solution to form hydrated hydrogel soft contact lenses.
• Methyl methacrylate and triethyleneglycol dimethacrylate were added and heating was continued for one hour at 89-93°C.
• Five drops of 2,5-dimethylhexane-2,5-diper-2-ethyl hexoate U.S.P. 245 U.S. Peroxygen Div., Whitco Chem. Co.
• the lens blanks were clear and of good optical quality.
• the hydration level was 34.5%.
• Triethyleneglycol dimethacrylate 1. 0 g Benzalkonium chloride salt of dimethylaminopropyl methacrylamide 0 .20 g 2,5-dimethylhexane-2,5-diper-2-ethyl hexoate 10 drops
• the above were blended thoroughly and cured at 85-95°C for two hours and 95-100°C for two hours.
• the lens blanks were clear and of good optical quality.
• the lens blanks were clear and of good optical quality.
• the above were blended thoroughly and cured at 85-95°C for two hours and 90-100°C for two hours.
• the lens blanks were clear and of good optical quality.
• the above were blended thoroughly and cured at 85-95°C for two hours.
• the lens blanks were clear and of good optical quality.
• the above mixture was blended until all of the pentachlorophenyl methacrylate dissolved.
• the mixture was placed in polyethylene molds and cured at 96°C for 1 hour and 40 minutes, and annealed for 3 1/2 hours at 85°C.
• the lens blanks had a hardness of 85-86D on top and 86-88D on the bottom. Two lenses were made, one had an equilibrium hydration level of 33.8% and the other 35.6%, the optics of both lenses were very good.
• the above were thoroughly mixed, with care to dissolve all of the solid components.
• the mixture was placed in molds in the oven at 95°C and cured for 1 hour and 45 minutes at 95°C and annealed for four hours and 15 minutes at 88°C.
• the lens blanks had a hardness of 83-88, and gave lenses with a hydration level of 32.4%.
• Example 10 2-hydroxyethyl methacrylate 100 . 00 g Methyl methacrylate 3 . 00 g
• the above were thoroughly mixed with care to dissolve all of the solid component.
• the mixture was placed in molds in the oven at 95°C and cured for one hour and 30 minutes at 95°C and annealed for two hours at 85°C.
• the blanks had a hardness of 84-86D and gave lenses with a hydration level od 34.5% with a yellow cast.
• the above were thoroughly mixed with care to dissolve all of the solid component.
• the mixture was placed in molds in the oven at 95°C and cured for one hour and 30 minutes at 95 °C and annealed for two hours at 85°C.
• the blanks had a hardness of 84-86D and gave lenses with a hydration level of 34.0%.
• the above were mixed thoroughly with care to dissolve all of the adamantane derivative.
• the mixture was placed in molds in the oven at 95°C and cured for one hour and 53 minutes at 95-96°C and annealed for three hours and 30 minutes at 86°C.
• the blanks had a hardness of 76-87D and gave lenses with a hydration level of 35.9%.
• the above were thoroughly mixed , with care , to dissolve all of the adamantane derivative.
• the mixture was placed in molds in the oven- at 95°C and was cured for one hour and 45 minutes at 94-95°C and annealed f or three hours and 30 minutes at 87°C.
• the blanks had a hardness- of 83-88D and gave lenses with a hydration level of 30.6%.
• the above were thoroughly mixed with care to dissolve the solid component.
• the mixture was placed in molds in the oven at 95°C and cured for one hour at 95°C.
• the temperature was raised to 110°C over a period of 8 minutes and the cured continued at 110°C for one hour.
• the blanks were annealed at 85°C for eight hours.
• the blanks had a hardness from 77-85D and gave lenses with a hydration level of 33.5%.
• the above were mixed thoroughly with care to dissolve all of the benzalkonium derivative.
• the mixture w-s placed in molds in the oven at 93°C and cured for one hour and 46 minutes at 93°C, and annealed for four hours at 86°C.
• the blanks had a hardness of 81-87D and gave lenses with a hydration level of 34.7%.
• the above were mixed thoroughly with care to dissolve all of the benzalkonium derivative.
• the mixture was placed in molds in the oven at 93°C and cured for one hour and 46 minutes at 93°C, and annealed for four hours at 86°C.
• the blanks had a hardness of 81-87D and gave lenses with a hydration level of 34.7%.
• the above were thoroughly mixed, with care to dissolve all of the benzalkonium derivative.
• the mixture was placed in molds in the oven at 94°C and cured for one hour and 45 minutes at 94°C and annealed for three hours and 30 minutes at 87°C.
• the blanks had a hardness of 87D and gave lenses with a hydration level of 27.0%.
• the above were mixed thoroughly with care to dissolve all of the benzalkonium compound.
• the mixture was placed in molds in the oven at 95°C and cured one hour and 46 minutes at 95°C.
• the blanks were annealed for eight hours at 85°C.
• the blanks had a hardness of 76-87D and gave lenses with a hydration level of 30.8%.
• the above were thoroughly mixed, with care to dissolve all of the hexene derivative.
• the mixture was placed in molds in the oven at 93°C and cured for one hour and 45 minutes at 93°C and annealed for four hours at 86°C.
• the blanks had a hardness of 82-87D and gave lenses with a hydration level of 34.7%.
• Example 22 2-hydroxyethyl methacrylate 50.00 g Methyl methacrylate 1.50 g Triethyleneglycol dimethacrylate 0.50 g 2-methacryloxyethyl-2,22-trichloro- 5-butyl carbonate 0.25 g 2,5-dimethylhexane-2,5-diper-2- ethyl hexoate (U.S.P. 245, U.S
• the above were thoroughly mixed, with care to dissolve all of the carbonate derivative of chlorobutanol.
• the mixture was placed in molds in the oven at 96 °C and cured for one hour and 45 minutes at 95-96°C, and annealed for three hours and 30 minutes at 85°C.
• the blanks had a hardness of 80-88D and gave lenses with a hydration level of 30.5%.
• Example 23 2-hydroxyethyl methacrylate 0 . 00 g Methyl methacrylate 3 . 00 g Triethyleneglycol dimethacrylate 1. 00 g N-vinylphenylsulfanilamide 0 . 05 g 2,5-dimethylhexane-2,5-diper-2- ethyl hexoate (U.S.P. 245, U.S.
• the above were thoroughly mixed, with care, to dissolve all of the solid component.
• the mixture was placed in molds in the oven at 95°C and cured for one hour and 45 minutes at 95°C and annealed for four hours at 85°C.
• the blanks had a hardness of 85-86D and gave lenses with a hydration level of 33.8%.
• the above were thoroughly mixed with care to dissolve all of the solid comoonent.
• the mixture was placed in molds in the oven at 95°C and cured for one hour and 45 minutes at 95°C and four hours at 85°C.
• the blanks had a hardness of 85-87D and gave lenses with a hydration level of 34.0%.
• N-methacryloxyethyl ethylene-diamine triacetic acid di sodium salt 0.10 g
• the above were mixed thoroughly with care to dissolve all of the solid components.
• the mixture was placed in molds in the oven at 95°C and cured for one hour and 30 minutes and annealed for two hours at 85°C.
• the blanks had a hardness of 85-87D and gave lenses with a hydration level of 34.6%.
• the above were thoroughly mixed, with care to dissolve all of the pentachlorophenyl methacrylate.
• the mixture was placed in molds in the oven at 96°C and cured for one hour and 40 minutes at 96 °C and annealed for three hours and 30 minutes at 85°C.
• the blanks had a hardness of 85-88D and gave lenses with a hydration level of 35.6%.
• the above were thoroughly mixed, with care, to dissolve all of the solid components.
• the mixture was placed in molds in the oven at 94°C and cured for one hour and 49 minutes at 94°C, and annealed for four hours at 88°C.
• N-adamantanyl methacrylamide 0.10 g 2,5-dimethylhexane-2,5-diper-2- ethyl hexoate (U.S.P. 245, U.S.
• the above were thoroughly mixed, with care, to dissolve all of the solid components.
• the mixture was placed in molds in the oven at 94°C and cured for one hour and 48 minutes at 94°C, and annealed for four hours at 88 °C.
• the above mixture was thoroughly mixed and then placed in molds in the oven.
• the mixture was cured at 83-86°C for one hour and 33 minutes and then annealed at 100°C for 1 hour, 100-125°C for 15 minutes, 125°C for 1 hour, 125-162°C for 30 minutes.
• the lens blanks were clear, had a dry hardness 84-86, lenses had a hydration level of 31.8%, and good optical quality.
• the above were blended thoroughly and cured at 65-66°C for 2 hours and 10 minutes and then at 100°C for 15 hours.
• the lens blanks were clear and of good optical quality with a hardness of 88-89D.
• lens blank polymers which include polymerically bound asepticizing agents made in accordance with this invention, as described hereinbefore, were tested and found to exhibit biostatic activity.
• this facet of the invention contemplates virtually any lens polymer which is comprised of the polymerization product of one or more monomers or prepolymers with one or more asepticizing agents wherein polymerization occurs by addition polymerization of ethylenically unsaturated carbon-carbon linkage, i.e., vinyl type polymerization of polymerizable vinyl groups on the lens monomer or prepolymer and on the asepticizing agent.
• Alternatives are examples of the lens polymer which is comprised of the polymerization product of one or more monomers or prepolymers with one or more asepticizing agents wherein polymerization occurs by addition polymerization of ethylenically unsaturated carbon-carbon linkage, i.e., vinyl type polymerization of polymerizable vinyl groups on the lens monomer or prepolymer and on the asepticizing agent.
• the two non-"vinyl” lens polymers (i.e., not formed by polymerization of an ethylenically unsaturated carbon-carbon, bond) of greatest interest are silicone lenses and cellulose acetate-butyrate lenses.
• Silicone lenses are siloxane polymers
• n is a large positive integer of from under 100 up to several thousand and R 1 or R 2 , or both, is typically methyl or phenyl but may often be lower alkyl and halogen substituted lower alkyIs.
• Known silicone monomers may be prepared in modified form to include a reactive group, e.g., -Cl, -OH, -NH 2 , on one of R 1 or R 2 .
• Asepticizing agents of the classes described in detail hereinbefore for example, may be reacted, directly, or through an intermediate reactive group, to attach to the siloxane monomer and which become an integrally bound part of the final polymeric lens.
• the general reaction scheme is typified by the following, in which particular monomers and asepticizing agents are merely exemplary:
• n and n are positive integers of about 10 to several thousand.
• alcoholic functional group which can be attached to the agent and then used to bond to the monomer through a transesterification reaction.
• the alcoholic functional group may also, by an epoxy addition reaction, be bonded to a monomer possessing an epoxy group.
• a functional group would be an isocyanate group which could be reacted with a hydroxy substituted monomer to produce a polymerically bound urethane asepticizing agent.
• An example would be to react the agent, phenyl isocyanate with a HEMA monomer. With polymerization, the parachlorophenol isocyanate reacts with the HEMA to form a polymerically bound urethane bacteriacide within the polymer matrix of the contact lens.
• Another example of a functional group would be an aldehyde which could be reacted with a HEMA monomer to produce an acetal linkage.
• Another variation of the principle of this invention is the reaction of an active group on an asepticizing agent directly or indirectly with an active group on cellulose acetate-butyrate.
• an active group on cellulose acetate-butyrate for example, para ⁇ hlorophenyl isocyanate can be reacted with a hydroxyl group on cellulose acetate-butyrate to bond an asepticizing agent to this lens material.
• para ⁇ hlorophenyl isocyanate can be reacted with a hydroxyl group on cellulose acetate-butyrate to bond an asepticizing agent to this lens material.
• the agents possessing the polymerizable group first and then graft polymerize the monomer mixture onto the polymerized agent.
• the monomer mixture may be polymerized to a low molecular weight prepolymer and then the agent possession a functional group may be polymerized to the prepolymer.
• this invention contemplates contact lenses and contact lens polymers produced from any monomer wherein there is chemically bonded to the polymer, either through polymerization bonding as exemplified by vinyl group polymerization, or chemically bonded to a monomer, prepolymer or polymer (as opposed to solid solutions, etc., for example) regardless of the specific polymers or asepticizing agents involved.
• this broad inventive concept there are many specific discoveries and inventions which are set forth in the preceding specification and which are recognized as inventions within the broad invention just described.
• Glavis, Frank J. Hamori, Eugene A.

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• 1980
  • 1980-06-10 WO PCT/US1980/000698 patent/WO1980002840A1/en not_active Application Discontinuation
  • 1980-12-30 EP EP19800901295 patent/EP0032905A4/de not_active Withdrawn

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