Silicone-hydrogel contact lenses with low protein absorption

FIELD: physics.

SUBSTANCE: method according to the invention involves adding to a reaction mixture an effective amount of a compound which reduces protein absorption, hardening said mixture in a mould to form a contact lens and removing the lens from the mould with at least one aqueous solution.

EFFECT: making silicone-hydrogel contact lenses with low protein adsorption, which are comfortable and safe to use, and do not require high production expenses.

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The SCOPE of the INVENTION

The present invention relates to silicone-hydrogel contact lenses with reduced absorption of proteins and to methods of manufacturing such lenses.

BACKGROUND of INVENTION

It is well known that contact lenses can be used for vision correction. Currently hydrogel contact lenses are very popular and often more convenient than a contact lens, made of solid materials.

Previously described contact lenses made from silicone hydrogel. However, some silicone hydrogel lenses absorb more protein than regular lenses. In addition, the number of absorbable protein for uncoated silicone hydrogel lenses increases, if attempts are made water extraction.

In some of the previously described methods were used only water. However, for such methods is characterized by a very long water leaching and / or high temperature for the extraction of undesirable components. The level of absorption of proteins these lenses were not determined.

There were also describes how to remove unwanted impurities from silicone-hydrogel lenses by leaching with the use of alcohols. The extraction of silicone hydrogel contact lenses alcohols usually reduces the absorption of protein compared the lenses, for which we used water extraction. Alcohols can cause a burning sensation in the eyes, so they must be completely removed from the contact lenses. For disposal of the alcohols required special processing stage, which makes the production process more expensive. In addition, the use of organic solutions may have other disadvantages, including, for example, to threaten security; to give an increased risk of downtime of the production line; to provide a high value solution to extract; to pose a threat to health associated with the use of organic solvents.

Thus, there is still a need for ways to reduce the absorption of proteins silicone hydrogel lenses, which differs from the methods of extraction with alcohol.

BRIEF description of the INVENTION

The present invention relates to silicone-hydrogel contact lenses formed from the reaction mixture, consisting of at least one of a silicone compound and reducing the absorption of proteins number of at least one reducing the absorption of protein compounds. The present invention also relates to a method for reducing protein deposition on contact lenses, comprising curing the silicone hydrogel reaction mixture containing at least one reducing the absolute is Blu proteins compound in reducing the absorption of protein quantity.

DETAILED description of the INVENTION

It was found that the absorption of proteins silicone hydrogel contact lenses can be reduced by adding at least one reducing the absorption of protein compounds in the reaction mixture, from which the manufactured contact lens. Previously, the deposition of proteins on the contact lens was reduced by coating on a contact lens or by extraction lenses solvents, for example alcohols. However, the application of a uniform coating can be a difficult task, since it requires additional process steps and equipment. On special stages of extraction also requires the use of additional equipment and expensive solvents which may require special manufacturing operations. The present invention provides a simple way of dramatically reducing the deposition of proteins.

Reduce the absorption of protein compounds are compounds that when added to the reaction mixture or in contact with this mixture reduces the reaction rate of at least one component of the reaction mixture, and, in some embodiments of the invention, reduces the reaction rate for the "most responsive" components, providing more than g is megenney reaction components. Classes reduces the absorption of protein compounds include inhibitors (or acceptors radicals), controls the degree of polymerization, the acceptors radicals controlled the sources of free radicals, and mixtures thereof, etc.

Inhibitors of free radicals are compounds that react quickly multiplying radicals with the formation of varieties of stable radicals, which stop the development of a chain reaction. Classes of inhibitors include quinones, substituted phenols, secondary aromatic amines, lactones and nitro compounds. Some examples of inhibitors include equivalent (OSH), onomatology ether of hydroquinone (MAGH), hydroxyamine, derivatives of benzophenone, molecular oxygen, vitamin E, a mixture of the nitric oxide/nitrogen dioxide (which forms a free nitroxyl radicals in the location), mixtures thereof, etc. In one variant of implementation of the present invention reduces the absorption of proteins compound contains at least one inhibitor.

Examples of classes of regulators degree of polymerization include alkylthiol, esters dithiocarbonic acid, mixtures thereof, etc. are Examples of controlled sources of free radicals include pseudo-living radical polymerization under the action of nitroxyl (NMP) (including the ones described in The Chemistry of Radical Polymerization, 2nd ed., Moad and Solomon, S. 472-479), glad the radical polymerization atom transfer (ATRP), including activated organic halide low molecular weight (including the ones described in The Chemistry of Radical Polymerization, 2nd ed., Moad and Solomon, S. 488-89 and 492-497), radical polymerization with reversible chain transfer (RAFT), including thiocarbonyldi-reagents (for example, described in The Chemistry of Radical Polymerization, 2nd ed., Moad and Solomon, S. 508 to 514). In the case of the use of controlled sources of free radicals they are used as part or as a whole system is the initiator.

The term "protein" in the context of this document includes proteins that are normally found in the eyes, including the tear film. These proteins include both active and denatured proteins. Examples of proteins that are normally found in the tear film include lysozyme, lactoferrin, lipocalin, glycoprotein, albumin, a heavy chain immunoglobulin (IgHC), light chain immunoglobulin (IgLC), mixtures thereof, etc. In some embodiments of the invention reduced absorption denaturirovannykh proteins. Presumably, some proteins, such as lysozyme and lactoferrin (in active form), have a neutral or positive effect on the process of wearing contact lenses. In some embodiments of the invention reduced the absorption of proteins other than lysozyme and lactoferrin, to less than 5 μg per lens. The term "effective amount reduces the absorption of proteins connect the Deposit" means the amount which reduces the absorption of protein compounds, sufficient to reduce the absorption of at least 10% of contact lens at least one protein from a fluid, such lacrimal, in comparison with lenses, in which the quantity of reducing the absorption of proteins connection is less than a specified effective amount. In other embodiments of the invention, the absorption of proteins other than lactoferrin and lysozyme, is reduced by at least 10%, and in some other embodiments of at least 20% in comparison with the lens without intentionally added to reduce the absorption of protein compounds. In other embodiments of the invention, the absorption of all the proteins is reduced by at least 10%, and in some other embodiments of at least 20% in comparison with the lens without intentionally added to reduce the absorption of protein compounds.

Reduces the absorption of protein compounds are added in quantities sufficient to obtain a lens with a total absorption of proteins below 15 micrograms per lens, and in some other embodiments of below 10 µg per lens. The number reduces the absorption of protein compounds, used or added to the composition will depend on a number of factors, including the effectiveness of reducing the absorption of protein compounds, ophthalmic compatibility reduces the absorption of proteins and conc is ntrace other reduces the absorption of protein compounds. Efficiency reduces the absorption of protein compounds may affect both the lower and upper concentration value in the present invention. For example, among the compounds used, is equivalent (BCT) is the only reducing the absorption of protein connection. The concentration of OSH less than 600 parts per million provide a small decrease in the absorption of proteins. However, if the molar concentration reduces the absorption of proteins of connections is greater than the molar concentration of the source of free radicals, then it may hamper the achievement of the required degree of curing. Therefore, compounds that reduce the absorption of proteins, should be added to the reaction mixture in quantities greater than 600 parts per million, but less than the amount that prevents complete curing of the polymer, or the amount by which the finished lens causes discomfort to the person who wears it.

In addition, if for example you use OSH, it is known that OSH can cause eye discomfort, and when this connection is part of the contact lens in the leached concentrations greater than approximately 2000 ppm. The term "ophthalmic discomfort" means the burning sensation or itching after installing contact lenses, which can on Itsa from several seconds to several minutes. The degree of eye discomfort caused by a component varies depending on its chemical structure and leachable concentration in the finished lens. When using OSH as reduce the absorption of protein compounds within the present invention, OSH must be present in the finished lens in concentrations of less than 3000 ppm, and in some other implementations - at concentrations in the region of 2,000 ppm or less; in some other implementations in concentrations of less than 1000 parts per million.

The number reduces the absorption of protein compounds present in the finished lens will depend on the concentration of reducing the absorption of protein compounds in components used, the number reduces the absorption of protein compounds added to the reaction mixture, and the conditions of the extraction. In the case when the present invention is used OSH as reduce the absorption of protein compounds, and extraction with alcohol number of OSH present in the reaction mixture, up to 2% by weight of the reaction mixture and diluent, in some embodiments of up to about 1% by weight, and in some other embodiments of up to about 0.5% by weight. However, when using water extraction to ncentrate OSH in the reaction mixture is less than 5000 parts per million, in some embodiments of approximately 3000 ppm or less, and in some other embodiments of less than 1500 parts per million.

In the composition reduces the absorption of protein compounds can also be used oxygen. The amount of oxygen in the reaction mixture can be determined using an oxygen analyzer, for example, oxygen analyzer Jenco 9250. A suitable amount of oxygen include amounts sufficient to reduce the absorption of proteins, but insufficient to adversely affect the quality or properties of the lens. Suitable dissolved oxygen concentration in the reaction mixture ranges from 1 to approximately 6 parts per million. Oxygen can be introduced by exposure to molds for casting lenses before loading the reaction mixture in molds for casting. Form for casting can be exposed to oxygen at a concentration of approximately 20% O2and , in some embodiments of approximately 10 to 20% O2. The exposure time is from one minute, in some embodiments of approximately 1 to 10 minutes, and in other embodiments of approximately 1 to 5 minutes. The necessary time of exposure may differ from the above time depending on the selected molding material. So, n is the sample, for molding materials that are more permeable to oxygen than Zeonor, you may need less than 5 minutes.

The reaction mixture within the present invention include all components (reactive and preaction-able) for forming the lenses of the present invention. The reaction mixture within the present invention include at least one of a silicone component, and may contain other known components, including hydrophilic components, wetting agents, photoinitiators, crosslinking agents, substances that block UV radiation, dyes, photochromic compounds, pharmaceutical and nutraceutical compounds, antimicrobial and antifungicide connection, connection for tinting, antiadhesive (tools for recovery), thinners, etc.

The term "components" includes monomers, macromer and prepolymers. The term "monomer" refers to compounds with a low molecular weight, which can be polymerized to compounds with higher molecular weight, polymers, macromeris or prepolymers. The term at macromer herein means capable of polymerization, a compound with high molecular weight. The prepolymers is partially polymerized monomers or monomers capable of further polymerization.

"Containing silicone comp the element" - this component, which contains at least one group [-Si-O-] in the monomer, macromer or prepolymer. In one implementation options of the total number of Si atoms and associated O atoms present in the containing silicone component in the amount of more than 20% by weight, and in another embodiment, the implementation of more than 30% of the total molecular weight of a silicone component. Suitable silicon based components contain capable of polymerization functional groups such as acrylate, methacrylate, acrylamide, methacrylamide, vinyl, N-vinylacetat, N-vinylamide and sterilnye functional groups. Useful for the purposes of the present invention examples containing silicone components can be found in the patent applications U.S.№3808178; №4120570; №4136250; №4153641; №4740533; №5034461 and no 5070215, as well as in the application No. EP080539. In the above references describes numerous examples of olefin-containing silicone components.

Along with what can be included in almost any containing silicone component, in one embodiment, the implementation of the present invention, in which the module should not exceed approximately 827,4 kPa (120 psig), a large part of the mass fraction of the silicone components used in the formulation of the lens, should contain only one capable of polymerization functional group containing monofunctional forces the con component"). In this implementation, to ensure the necessary balance between the ability to pass oxygen and module, it is preferable that all components that have more than one capable of polymerization functional group ("multi-component") amounted to no more than 10 mmol/100 g of reactive component, and preferably not more than 7 mmol/100 g of reactive component.

Suitable silicon based components include the compounds of formula I

where R1independently selected from monovalent reactive groups, monovalent alkyl groups, or monovalent aryl groups, any of these groups, which may optionally contain functional hydroxy, amino, oxa, carboxy, alkylcarboxylic, alkoxy, amido, carbonate, urethane group, halogen or combinations thereof; and a monovalent siloxane chain comprising from 1-100 repeating units of Si-O, which may contain additional functional alkyl, hydroxy, amino, oxa, carboxy, alkylcarboxylic, alkoxy, amido, urethane group, a halogen, or mixtures thereof;

where b = 0 to 500, it means that if b is non-zero, then b has a distribution with a fashion equal to the specified value.

moreover, at least one piece of R1the stand is made by a monovalent reactive group, in some embodiments of the present invention from one to three fragments of R1represent a monovalent reactive group.

Used in this application, the term "reactive group" refers to groups capable of free radical reactions and (or) cationic polymerization. Typical, but not limiting examples of free radical reactive groups include (meth)acrylates, sterile, vinyls, vinyl ethers, C1-6the alkyl(meth)acrylates, (meth)acrylamide, C1-6the alkyl(meth)acrylamide, N-vinylacetate, N-vinylamide, C2-12alkenyl, C2-12alkenylphenol, C2-12alkenylacyl, C2-6alkenylphenol-C1-6alkali, O-vinylcarbazole and O-vinylcarbazole. Typical, but not limiting examples of cationic reactive groups include vinyl ester or epoxy groups, and mixtures thereof. In one embodiment, the implementation of the present invention the free radical reactive groups include (meth)acrylates, aryloxy, (meth)acrylamide, and mixtures thereof.

The objectives of the present invention monovalent alkyl and aryl groups include unsubstituted monovalent C1-C16alkyl group, a C6-C14aryl group such as substituted and unsubstituted methyl, ethyl, propyl, and b is Teal, 2-hydroxypropyl, propoxyphen, polyethylenoxide, as well as their various combinations, etc.

In one embodiment, the implementation of the present invention b is zero, one piece of R1represents a monovalent reactive group, and at least three fragments R1selected from monovalent alkyl groups containing one to 16 carbon atoms, and in another implementation of monovalent alkyl groups containing from one to 6 carbon atoms. Typical, but not limiting examples containing silicone components of this implementation of the present invention include 2-methyl-,2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester (SiGMA), 2-hydroxy-3-methacryloxypropyl-Tris(trimethylsiloxy)silane,

3-methacryloxypropyl(trimethylsiloxy)silane (TRIS),

3-methacryloxypropyl(trimethylsiloxy)methylsilane and

3-methacryloxypropyltrimethoxysilane.

In one embodiment, the implementation of the present invention b is in the range from 2 to 20, 3 to 15, or, in some implementations, from 3 to 10; at least one terminal fragment of R1represents a monovalent reactive group, and the remaining fragments of R1selected from monovalent alkyl groups containing one to 16 atom is in carbon, in another implementation of monovalent alkyl groups containing from one to 6 carbon atoms. In another variant implementation of the invention b is from 3 to 15, one end group, R1represents a monovalent reactive group, which may further be substituted by at least one hydrophilic group such as hydroxyl, ether or mixtures thereof, the other end group, R1represents a monovalent alkyl group having from 1 to 6 carbon atoms and the remaining R1represents a monovalent alkyl group having from 1 to 3 carbon atoms. Non-limiting examples of silicone components of the present invention include polydimethylsiloxane end (mono-(2-hydroxy-3-methacryloxypropyl)-propyl-ether groups (molecular weight 400-1000)) (HO-mPDMS), polydimethylsiloxane end manometrically group with nite mono-n-butilkoi group (molecular weight of 800-1000), (mPDMS).

In another embodiment implementation of the present invention b is in the range from 5 to 400, or from 10 to 300, both terminal fragment of R1represent a monovalent reactive group, and the remaining fragments of R1independently selected from monovalent alkyl groups containing from one to 18 carbon atoms, which mo is ut to be essential bridging group between carbon atoms and can also contain halogen atoms.

In another implementation of the present invention from one to four fragments of R1are vinylcarbene or vinylcarbene with the following formula:

Formula II

where Y denotes O, S or NH-;

R denotes hydrogen or methyl;

q is 1, 2, 3 or 4; and

b is from 1 to 50.

More specifically, vinylnorbornene or vinylcarbene containing silicone monomers include 1,3-bis[4-(vinyloxycarbonyloxy)buta-1-yl]tetramethyldisiloxane; 3-(vinyloxycarbonyl)-propyl-[Tris(trimethylsiloxy)silane]; 3-[Tris(trimethylsiloxy)silyl]-propylaniline; 3-[Tris(trimethylsiloxy)silyl]-propylenecarbonate; trimethylsilylcyanation; trimethylsilylmethylamine and

If you need a biomedical device with modulus less than 200, only one of the fragments of R1must be a monovalent reactive group, and not more than two of the remaining fragments of R1must be a monovalent siloxane group.

In one embodiment of the invention, in which the necessary silicone hydrogel lenses, the lens in accordance with the present invention will be made from the reaction mixture, containing at least 20% by weight, and in some embodiments is approx the tion from 20 to 70% by weight of a silicone component, calculated on the total weight of reactive monomer components, made from polymer.

Another class containing silicone component comprises polyurethane macromer with the following formula:

Formula IV-VI

(*D*A*D*G)a*D*D*E1;

E(*D*G*D*A)a*D*G*D*E1; or

E(*D*A*D*G)a*D*A*D*E1

where

D denotes alkyl biradical, alkylcyclohexanes biradical, cycloalkenyl biradical, the aryl biradical or alcylaryl biradical containing from 6 to 30 carbon atoms;

G denotes alkyl biradical, cycloalkenyl biradical, alkylcyclohexanes biradical, the aryl biradical or alcylaryl biradical containing from 1 to 40 carbon atoms which may have in a main chain ether, thioester or amine bridge group;

* indicates a urethane or ureido-bridge group;

aequal to at least 1;

A means divalently polymer moiety with the following formula:

Formula VII

R11independently denotes an alkyl or fluorine-substituted alkyl group having from 1 to 10 carbon atoms which may contain ether linkages between carbon atoms; y is at least 1; p denotes the mass of the molecule from 400 to 10,000; each of the groups E and E1independently denotes capable of polymerization of unsaturated organic radical, pre is raised by the formula:

Formula VIII

where R12denotes hydrogen or methyl; R13denotes hydrogen, an alkyl radical having from 1 to 6 carbon atoms, or the radical-CO-Y-R15where Y is-O-,Y is-S - or-NH-; R14means divalently radical having from 1 to 12 carbon atoms; X represents-CO - or-OCO-; Z denotes-O - or-NH-; Ar denotes an aromatic radical having from 6 to 30 carbon atoms; w is 0 to 6; x is 0 or 1; y is 0 or 1 and z is 0 or 1.

In one embodiment, the implementation of the present invention contains a silicone component is a polyurethane macromer, represented by the following formula:

Formula IX

where R16is biradical of a diisocyanate after removal of the actual isocyanate group, for example, biradical isophorondiisocyanate. Other containing silicone micromera appropriate to the purposes of the present invention, is a compound according to formula X (where x+y is a number in the range from 10 to 30), obtained by reaction of Ftorafur, polydimethylsiloxane with terminal hydroxyl group, isophorondiisocyanate and isocyanatoacetate.

Formula X

Other containing silicone components corresponding to the object of the present invention include components is s, described in the patent application WO 96/31792, such as macromer containing polysiloxane, polyalkylene, diisocyanate, policeregistered, poliferation and polysaccharide groups. Another class containing silicone components containing silicone macromer prepared by the method of polymerization with the transfer of the group (GTP), for example, macromer described in U.S. patent No. 5314960, 5331067, 5244981, 5371147 and 6367929. In applications for U.S. patent No. 5321108; No. 5387662 and No. 5539016 described siloxanes with polar fluorinated graft or side group having a hydrogen atom at the terminal diversional a hydrogen atom. In the application for U.S. patent No. 2002/0016383 described hydrophilic siloksanchlorides containing essential and diloxanide bridge group, and suitable for cross-linking monomers containing polyester and polysiloxane group. Any of the above polysiloxanes can also be used as a silicone component in the framework of the present invention.

The reaction mixture may also contain at least one hydrophilic component. Hydrophilic monomers may be any of the known hydrophilic monomers suitable for the manufacture of hydrogels.

One class of suitable hydrophilic monomers include acrylic and vinylstyrene monomers. Such gerofi the performance communications monomers can be used as cross-linking agents, however, where use of hydrophilic monomers having more than one is capable of polymerization functional groups, their concentration should be limited as described above, to obtain a contact lens having the desired module. The terms "vinyl-type" or "vinylstyrene" monomers are monomers containing a vinyl group (-CH=CH2) and are generally highly reactive. It is known that such hydrophilic vinylstyrene monomers relatively easily polymerized.

Monomers "acrylic-type" or "allstargame" monomers are monomers containing the acrylic group (CH2=CRCOX), where R is H or CH3X denotes O or N, which are known to also easily polymerized, for example, N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), glycomolecules, 2-hydroxyethylmethacrylate, polietilenglikolmonostearat, methacrylic acid and acrylic acid.

Hydrophilic vinylstyrene monomers that can be added to the silicone hydrogels of the present invention include such monomers as N-vinylamide, N-vinylacetate (for example, N-vinyl pyrrolidone (NVP)), N-vinyl-N-methylacetamide, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformate, N-vinylformamide, while it is preferable to NVP.

Other hydrophilic monomers, the cat is which can be used in the present invention, include polyoxyethylene polyols having one or more terminal hydroxyl groups, substituted functional groups, capable of containing polymerization of the double bond. Examples of such monomers include polyethylene glycol, an ethoxylated Alkylglucoside and ethoxylated bisphenol A reacted with one or more molar equivalents closing groups, such as isocyanatoacetate (IEM), methacrylic anhydride, methacryloylamido, vinylbenzoate and similar compounds, with the formation of poliatilenglikola having one or more end-curable olefinic groups associated with poliatilenglikola through a connecting group such as a carbamate or ether group.

Other examples include hydrophilic vinylcarbene or vinylcarbene monomers described in U.S. patent No. 5070215, and hydrophilic oksazolonovye monomers described in U.S. patent No. 4910277. Other suitable hydrophilic monomers are well-known specialist in this field.

In one embodiment, the implementation of the present invention the hydrophilic properties of at least one hydrophilic monomer, such as DMA, HEMA, glycomolecules, 2-hydroxyethylmethacrylate, NVP, N-vinyl-N-methylacrylamide, polietilenglikolmonostearat, methacrylic acid and acrylic acid is, the most preferred monomer is DMA.

The concentration of the presence of hydrophilic monomers can vary considerably, depending on the specific combination of required properties. Is acceptable concentration of hydrophilic monomers to about 50, and preferably from about 5 to 50% by weight in terms of all reactive components. For example, in one implementation options of the lenses of the present invention have a water content of at least about 25%, and in another embodiment, the implementation is from about 30 to 70%. For these options, the implementation of the hydrophilic monomer may be included in amounts of from about 20 to 50% by mass.

Other components that may be present in the reaction mixture and used for the formation of contact lenses in the framework of the present invention, include wetting agents, for example, described in U.S. patent No. 6367929, international patent number WO03/22321, WO03/22322, components, improves the compatibility, for example, described in U.S. patent No. 2003/162862 and 2003/2003/125498, compounds that absorb ultraviolet radiation, drugs, antimicrobial compounds, capable of copolymerization and depolymerizes dyes, antiadhesive, reactive compounds for tinting, pigments, their compounds and the like

In the reaction mixture may be added to the polymerization catalyst. The polymerization initiators include compounds such as laurelbrooke, benzoyl peroxide, isopropylparaben, azobisisobutyronitrile etc. that are sources of free radicals at moderately elevated temperatures, and fotosensibiliziruyuschimi systems, such as aromatic alpha hydroxyketone, alkoxycarbonyl, acetophenone, arylphosphonate, besatisfied, and Quaternary amine plus a diketone, mixtures thereof and the like, Examples of photoinitiators are 1-hydroxycyclohexyl, 2-hydroxy-2-methyl-1-phenyl-propane-1-he, bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylphosphine (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphine (Irgacure 819), 2,4,6-trimethylbenzenesulfonamide and 2,4,6-trimethylbenzenesulfonamide, benzoylmethylene ether and a combination of camphoroquinone and ethyl 4-(N,N-dimethylamino)benzoate. To commercially available visible light initiators include Irgacure 819, Irgacure 1700, Irgacure 1800, Irgacure 819, Irgacure 1850 (production Ciba Specialty Chemicals) and the initiator Lucirin TPO (manufactured by BASF). To a commercially available UV photoinitiators include Darocur 1173 and Darocur 2959 (Ciba Specialty Chemicals). These and other photoinitiator, which can be used are described in volume III, Photoinitiators for Free Radical Cationic &Anionic Photopolymerization, 2thedition, J.V. Crivello&K. Dietliker; p is on the editorial Board G. Bradley; John Wiley and Sons; New York; 1998. The initiator used in the reaction mixture in an effective amount to initiate the photopolymerization reaction mixture, for example, from about 0.1 to about 2 weight parts per 100 parts reacts monomer. The polymerization reaction mixture can be initiated by proper selection of heating or visible or ultraviolet light or other means, depending on the initiator of polymerization. Otherwise, the initiation can be done without photoinitiator using, for example, e-beam. However, if you use photoinitiator, the preferred initiators are besatisfied, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine (Irgacure 819®) or a combination of 1-hydroxycyclohexanone and bis(2,6-dimethoxybenzoyl)-2,4-4-tributyltinoxide (DMBAPO), in another embodiment, the implementation of the preferred method of initiating polymerization is the activation of visible light. The preferred initiator is bis(2,4,6-trimethylbenzoyl)-phenylphosphine (Irgacure 819®).

Reactive components (containing silicone component, hydrophilic monomers, wetting agents and other components, which react in the formation of the lens) are mixed together with a diluent or without it, and form a reaction mixture.

In od the om implementation options of the used solvent has a polarity, sufficient to solubilize non-polar components in the reaction mixture in the reaction conditions. One of the ways of describing the polarity of the solvents of the present invention is the solubility parameter Hansen, δp. In some embodiments of δp is less than 10 and preferably less than 6. Suitable diluents are described in U.S. patent No. 60/452898 and 6020445.

Classes of suitable diluents include, inter alia, alcohols having from 2 to 20 carbon atoms, amides having from 10 to 20 carbon atoms and are derived from primary amines, ethers, polyethers, ketones having from 3 to 10 carbon atoms, and carboxylic acids having from 8 to 20 carbon atoms. For all solvents with increasing number of carbon atoms can be also increased the number of polar functional groups to ensure proper Miscibility with water. In some embodiments of the preferred are primary and tertiary alcohols. Preferred classes include alcohols having from 4 to 20 carbon atoms, and carboxylic acids having from 10 to 20 carbon atoms.

In one embodiment of the invention the solvent is selected from those diluents that are to some extent soluble in water. In some embodiments of the amount of diluent miscible with water, is on ENISA least about three percent. Examples of the water-soluble diluents are: 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, tert-amyl alcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, cekanova acid, octanoic acid, dodekanisa acid, 1-ethoxy-2 - propanol, 1-tert-butoxy-2-propanol, EH-5 (provider - Ethox Chemicals), 2,3,6,7-tetrahydroxy-2,3,6,7-tetramethylpentane, 9-(1-methylethyl)-2,5,8,10,13,16-hexoctahedron, 3,5,7,9,11,13-hexamethoxy-1-tetradecanol, mixtures thereof, etc.

The reaction mixture within the present invention can be overiden using any known method of forming the reaction mixture in the production of contact lenses, including centrifugal casting and static casting. Methods of centrifugal casting is described in U.S. patent No. 3408429 and 3660545 and methods "static" casting described in U.S. patent No. 4113224 and 4197266. In one implementation options of the contact lens in the framework of the present invention is produced by molding a silicone hydrogels, which is a cost-effective way and allows you to precisely control the final shape of the hydrated lens. When using this method, the reaction mixture is placed in a mold having the geometrical form, which must give a finished silicone hydrogel, i.e. n is bohsia water from the polymer. The reaction mixture is exposed to such conditions under which polymerize the monomers, resulting in a gain polymer having approximately the following form, which is necessary for the final product.

After curing, the lens is subjected to extraction to remove unreacted components, and then remove the lens from the mold for casting lenses. The extraction can be carried out using conventional extracting liquids, certain organic solvents, such as alcohols, or may be conducted by extraction using aqueous solutions.

Aqueous solutions are solutions that contain water. In one implementation options of the aqueous solutions in the framework of the present invention contain at least about 30% water, in some embodiments of at least about 50% water, in some embodiments of at least about 70% water, and in others at least about 90% by weight of water. Aqueous solutions may also include additional water-soluble components, such as antiadhesive, wetting agents, additives reduce friction, pharmaceutical and nutraceutical components, mixtures thereof, etc. Antiadhesive are compounds or mixtures of compounds that in combination with water to reduce the time that is required for to remove the contact lens from the mold for casting lenses, in comparison with the time required to extract such a lens when using an aqueous solution containing no release agent. In one implementation options of the aqueous solutions contain less than 10% by weight, and in another embodiment less than 5% by weight of organic solvents, such as isopropyl alcohol, in addition, in another embodiment, the implementation of the solutions do not contain organic solvents. In these embodiments of aqueous solutions do not require special handling, for example, cleaning, recycling or special disposal procedures.

In various embodiments of the extraction can be performed, for example, by immersing the lens in an aqueous solution or by exposure to the lens of the flow of an aqueous solution. In various embodiments of the extraction may also include, for example, one or more operations: heating the aqueous solution; mixing an aqueous solution; the improvement of the content of antiadhesive in aqueous solution to a level sufficient to remove the lens from the mold; mechanical or ultrasonic agitation lenses; adding an aqueous solution of at least one leaching funds sufficient to ensure adequate removal of unreacted components and the lens.

The extraction may be carried out in various ways without limitation, for example, by using the periodic process, during which the lenses are immersed in the solution, which is in a stationary vessel for a certain period of time, or vertical process, during which the lens is exposed to a continuous stream of an aqueous solution.

In some embodiments of the aqueous solution can be heated using a heat exchanger or other heating apparatus to further facilitate the leaching of the lens and remove lens from the mold for casting. For example, heating may include increasing the temperature of the aqueous solution to the boiling point when immersed hydrogel lens and form, which are attached to the lens, in a heated aqueous solution. Other implementations may include controlled cyclic change of temperature of the aqueous solution.

Some implementations may also include the use of physical mixing to promote leaching or extraction. For example, some forms of lenses, with which the contact lens can vibrate or move back and forth in aqueous solution. Other options for implementation may include the use of ultrasonic waves in water solution.

These and similar methods can avlat the Xia acceptable ways to release the lens.

Used herein, the term "lens retrieved from" means that the lens is either completely separated from the form, or only loosely attached and can be easily removed with a light shake or shifted by means of a tampon. Used in the present invention, the conditions include a temperature of less than 99°C in a period of time approximately equal to less than 1 hour.

It was found that adding at least one reducing the absorption of proteins compound also improves the ability of the lens to be removed from the form when using water extraction. Lenses formed from reaction mixtures containing at least one reducing the absorption of proteins compound that is extracted from the molds easier, and they found a smaller number of edge defects such as chipping or chipping. In some embodiments, the implementation is achieved by reducing the number of edge defects by at least 20%. In some implementations to reduce the number of edge defects in the reaction mixture is added at least one reducing the absorption of proteins compound that acts in conjunction with the handling of oxygen moulds for casting lenses before settling back generatrix forming on the front, containing the reaction mixture. The types and amounts of reducing the absorption is elkow compounds described above. The right time is also described above.

The lens in the framework of the present invention require minimal processing after fabrication. Processing after fabrication is an optional part of the manufacturing process and includes the change of solution and extraction, but not sterilization, storage and balancing. In those implementations, which provide treatment after fabrication, it is produced by aqueous solutions for at least 6 hours, in some embodiments of less than 4 hours less than 2 hours and (sometimes) less than 1 hour.

Treated lenses can be sterilized by known methods, for example, without limitation, by autoclaving.

It should be understood that all operations described in this document tests have some degree of inaccuracy inherent in the way of their conduct. Accordingly, the results should not be considered as absolute values, but as the field of numerical values, limited by the accuracy of a particular test method.

To illustrate the invention the following examples. The examples do not limit the invention. They are intended only to suggest practical use of the invention. Experts in the field of contact lenses and other areas will be able to find other ways of practical use of the project for the invention. However, these methods will be considered as falling within the scope of the present invention.

EXAMPLES

In the following examples, the following abbreviations are used:

SiGMA2-methyl-,2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester 2-propanolol acid
DMAN,N-dimethylacrylamide
GAME2-hydroxyethylmethacrylate
mPDMSthe polydimethylsiloxane end manometrically and mono-n-butilkoi groups and a molecular weight of 800-1000 MW (Mn)
Norbloc2-(2'-hydroxy-5-methacryloyloxyethyl)-2H-benzotriazol
CGI 1850a mixture of 1-hydroxycyclohexanone and bis(2,6-dimethoxybenzoyl)-2,4-4-tributyltinoxide in the ratio of 1:1 by weight
FSBphosphate-saline buffer solution
PVPpoly(N-vinyl pyrrolidone) (K values specified)
Blue G IS MA the reaction product is active (blue Reactive Blue 4 and GAME as described in Example 4 of U.S. patent No. 5944853

IPSisopropyl alcohol
DO3,7-dimethyl-3-octanol
HO-mPDMSthe polydimethylsiloxane end mono-(3-methacrylate-2-hydroxypropoxy), sawn and monobutyl group
EGDMAetilenglikolevykh
TEGDMAtetraethylethylenediamine
TPGMEtripropyleneglycol ether
ALEcleopathra fluid prepared in accordance with the procedure below
CGI 819bis(2,4,6-trimethylbenzoyl)-phenylphosphine
OSHequivalent
MAGHonomatology ether of hydroquinone

The mother solution of albumin: a solution album is 1 mg/ml, diluted FSB ratio 1/20 to obtain a stock solution of bovine serum albumin (50 mg/ml

Buffer solution letpadaung fluid (ALE):

Buffer solution letpadaung liquid (buffer ALE) was prepared by adding 0,137 g sodium bicarbonate (Sigma, S8875) and 0.01 g of D-glucose(Sigma, G5400) FSB containing calcium and magnesium (Sigma, D8662). Thus prepared solution ALE was stirred at room temperature until complete dissolution of all components (approximately 5 minutes).

Lipid mother solution was prepared by mixing the following lipids in solution ALE with careful stirring for approximately 1 hour at a temperature of approximately 60°C to obtain a clear solution:

Cholesterolemia (Sigma, C0289)24 mg/ml
Lineolata (Sigma, L2807)20 mg/ml
Triolein (Sigma, 7140)16 mg/ml
Propyl ester of oleic acid (Sigma, O9625)12 mg/ml
Undecylenoyl acid (Sigma, U8502)3 mg/ml
Cholesterol (Sigma, C8667)1,mg/ml

Lipid mother solution (0.1 ml) was mixed with 0.015 g of mucin (mucines from bovine submandibular gland (Sigma, M3895,Type 1-S)). To a mixture of mucin with lipids added three servings of solution ALE with a volume of 1 ml each. The resulting solution was stirred until all components in the solution (approximately 1 hour). To 100 ml was added the required amount of buffer solution ALE and thoroughly mixed.

Then one by one added the following components in the order to 100 ml of prepared above mucinosa-lipid mixture. Full time adding components accounted for approximately 1 hour.

Acidic glycoprotein from bovine plasma (Sigma, G3643)0.05 mg/ml
Fetal bovine serum (Sigma, F2442)0,1%
Gamma-globulins from bovine plasma (Sigma, G7516)0.3 mg/ml
β-lactoglobulin (lipocalin from cow's milk) (Sigma, L3908)1.3 mg/ml
Secrete lysozyme hen egg white (Sigma, L7651)2 mg/ml
Lactoferrin from cow colostrum(Sigma, L4765)2 mg/ml

The resulting solution was left overnight at 4°C. the pH of the solution was brought to 7.4 using 1N. HCl. The resulting solution was filtered and kept at -20°C until use.

In all examples, the intensity was measured using radiometer IL 1400A using sensor XRL 140A.

Comparative example 1

Reactive components and the diluent (tert-amyl alcohol), listed in table 1, were mixed by stirring or rotation for at least 3 hours at a temperature of approximately 23°C until complete dissolution of all components. The content of reactive components listed in mass% with respect to all reactive components and diluent in mass percent with respect to the final reaction mixture. Used mPDMS was subsequently analyzed on OSH, and was found to contain OSH approximately 10,000 parts per million. Used DMA and SiGMA were subsequently analyzed on MAGH, and was found to contain MAGH approximately 400 and 100 ppm, respectively. Under nitrogen, the reaction mixture was placed in a thermoplastic form for contact lenses (front and rear forming material of Zeonor® 1060R obtained from Zeon, Corp.) and irradiated using lamps TLDK 30W/03 under the following conditions: 3 mW/cm2 2and about 5 mW/cm2for approximately 4 minutes at a temperature of approximately 70°C (less than 3% O2). Form within 3 seconds, subjected to heat from an infrared heater (Surfaceigniter, LLC, model RC-052), equipped with a nozzle, which focuses the heat on the back of forming stabilized at a temperature of 800°C and was opened using the lifting pins. The lenses were removed, were extracted and hydrational as follows: in 100% deionized water for approximately 15 minutes at ambient temperature, in a mixture of isopropyl alcohol/deionized water in the ratio of 70:30 for about 15 minutes at 25°C and 100% deionized water at ambient temperature for approximately 15 minutes.

The lenses were Packed in borate-salt buffer solution in glass vials and sterilized for 20 minutes at 121°C.

Comparative example 2

Reactive components and the diluent (tert-amyl alcohol), listed in table 1, were mixed by stirring or rotation within at least about 3 hours at a temperature of approximately 23°C until complete dissolution of all components. The content of reactive components listed in mass% with respect to all reactive components and diluent in mass percent with respect to the final reaction mixture. Used mPDMS was subsequently analyzed on OSH, and was found to contain OSH approximately 10,000 parts per million. Used DMA and SiGMA were subsequently analyzed on MAGH, and was found to contain MAGH approximately 400 and 100 ppm, respectively. Under nitrogen, the reaction mixture was placed in a thermoplastic form for contact lenses (front forming material of Zeonor® 1060R supplied from Zeon, Corp., and forming the rear is made from a mixture of material 55:45 Zeonor® 1060R:polypropylene) and irradiated using lamps TLDK 30W/03 under the following conditions: 1.5 mW/cm2within about 30 seconds at a temperature of approximately 50°C (less than 1% O2and about 5 mW/cm2for approximately 4.5 minutes at a temperature of approximately 70°C (less than 3% O2). Form within 3 seconds, subjected to heat from an infrared heater (Surfaceigniter, LLC, model RC-052) equipped with a nozzle, which focuses the heat on the back of forming stabilized at a temperature of 800°C and was opened using the lifting pins. The lenses were removed, were extracted and hydrational in deionized water under the following conditions: approximately 6 minutes at 10°C, about 6 minutes at 90°C and about 6 minutes at 45°C.

The lenses were Packed in borate-salt puff the RNA solution in glass vials and sterilized for 20 minutes at 121°C.

Table 1
Components:weight%
SiGMA30
mPDMS 100022
DMA31
GAME8,5
EGDMA0,75
Norbloc1,5
Blue GAME0,02
PVP K906
CGI 8190,23
Total monomers60%
PVP K1211
tert-amyl alcohol29
Total diluent40%

Lenses manufactured in comparative examples 1-2 were evaluated to determine the absorption of protein by the method 1.

Method 1: method daily incubation

Lenses (six copies of each of the subjects types) wet the removal packing solution and aseptically, using sterile forceps, transferred to 24-well cluster for cell cultures (one lens in each well). In each well contained 0.3 ml of ALE.

Lenses were incubated in ALE at 35°C, stirring rotation for 5 hours per day. After each incubation period in ALE lens was removed from the 24-hole cluster for cell cultures and were soaked overnight in a universal solution Complete Moisture Plus. This procedure was repeated every day during the time specified in the examples. At the end of the incubation period was measured efficiency of absorption of proteins after triple rinsing of the test lenses in three separate vials with phosphate-saline buffer solution.

The level of absorption of the proteins were determined by the method of analysis using bikinni acid (set QQP-BCA, Sigma)following the manufacturer's instructions of the kit. Was a standard curve constructed using part of the set of QP-BCA solution of albumin.

24-hole tablets marked and prepared standard solutions of albumin, adding the mother solution of albumin in phosphate-saline buffer (FSB), as shown in table 2 below:

Table 2
Tube No.FSB (ál)Mat. the-R albumin (ál) Final conc. (ág/ml)
1100000
2990100,5
39001005
480020010
560040020
640060030

Prepared fresh reagent QP-BCA, mixing 25 parts of reagent QA with 25 parts of reagent QB and 1 part of reagent QC (copper sulfate (II)), as described in the instructions to the set of Sigma QP-BCA. Prepared this amount of reagent, which was enough for all control and test samples of lenses, as well as for standard samples, and therefore took an equal volume of reagent QP-BCA on each volume of the FSB in the sample/standard.

To each sample was added an equal volume of reagent QP-BCA (1 ml for lenses in 1 ml of the FSB).

Standard samples, samples of lenses and races the thieves were incubated at 60°C for 1 hour, and then gave the samples to cool for 5-10 minutes. Then on the spectrophotometer measured the optical absorption of the solution at 562 nm.

Method 2: method for continuous incubation

Lenses (six copies of each of the types to be scanned) wet removal packing solution and aseptically, using sterile forceps, transferred to 24-well cluster for cell cultures (one lens in each well). In each well contained 1 ml of ALE.

Lenses were incubated in 1 ml of ALE at 35°C, stirring rotation within the time specified in the examples. The solution ALE in the wells was replaced every 24 hours. At the end of the incubation period was measured by the absorption of proteins after triple rinsing of the test lenses in three separate vials with phosphate-saline buffer solution. Measuring the absorbance of proteins was performed according to the method of bicinchoninic acid following the same procedure as described above.

Examples 1-16

Reactive components and the diluent (tert-amyl alcohol), listed in table 1, OSH and MAGH (concentrations indicated in table 4) were mixed by stirring or rotation for at least 3 hours at a temperature of approximately 23°C until complete dissolution of all components. The content of reactive components listed in mass% is tah against all reactive components, and diluent in mass percent with respect to the final reaction mixture. Before adding to the reaction mixture of mPDMS removed OSH (up to concentrations of about 13 parts per million OSH). The indicated concentration of OSH and MAGH represent the total concentration of compounds, including inhibitors in the composition of other components, such as mPDMS, SiGMA and DMA and added OSH and MAGH.

To form lenses were outdoors within the time specified in table 4. In ambient conditions (air), the reaction mixture was placed in a thermoplastic form for contact lenses having base compositions forming listed in table 4 (where % denotes % Zeonor®1060R in a mixture of Zeonor-polypropylene), and the rear form, made from a mixture of 55:45 Zeonor®1060R:polypropylene. The completed forms were then irradiated using lamps TLDK 30W/03 under the following conditions: 2 mW/cm2for about 25 seconds at a temperature of approximately 60°C and approximately 4 mW/cm2within about 5 minutes at a temperature of approximately 80°C (less than 3% O2). Form within 3 seconds, subjected to heat from an infrared heater (Surfaceigniter, LLC, model RC-052), stabilized at a temperature of 800°C and was opened using the lifting pins. The lenses were removed, extragear the Wali and hydrational in deionized water under the following conditions: approximately 6 minutes at 5°C, approximately 6 minutes at 90°C and about 6 minutes at 45°C.

The lenses were Packed in borate-salt buffer solution in glass vials and sterilized for 20 minutes at 121°C.

3, 6 and 10 days was measured by the absorption of protein by the method 1, as described in comparative example 1. The results are shown in table 4.

Table 4
Ave. No.[OSH]
parts per million
[MAGH]
parts per million
Time impacts O2on the form (s)BC (%)The exposure time (s)The absorbance of protein (μg/lens)
3 days6 days10 days
113400205512016±0,415±0,314±0,2
213400202016±0,315±0,415±0,4
313400300552014±0,414±114±1
41340030010012014±0,414±0,914±0,9
5138003001002011±112±111±0,8
6138002010012013±0,213±0,213±0,2
713800 3005512010±0,511±0,811±0,7
81380020552013±0,213±113±0,6
92004003001002013±0,913±0,813±0,8
1020040020552014±0,415±0,414±0,8
112004003005512012±0,611±0,612±0,7
12200 4002010012014±0,614±0,714±0,2
1320080030010012010±19±1,98±1,7
14200800205512011±0,811±0,810±0,4
15200800201002011±0,811±0,511±0,8
1620080030055209±0,79±0,99±0,8

From table 4 it is seen that increasing the s concentration of any of the compounds, OSH or MAGH, or time of oxygen exposure on the form reduces the absorption of proteins. Examples with the highest concentration of inhibitors (examples 16 and 13) show the lowest precipitation of proteins. Table 4 also shows that the composition forms (BC% is the % of material Zeonor in the base generatrix) and the dwell time of the reaction mixture in the form before curing does not affect the absorption of proteins.

Examples 17-25

Repeated comparative example 1 with the following changes: mPDMS was cleared before adding to the reaction mixture to a concentration of OSH approximately 100 ppm, the reaction mixture was added an additional inhibitor, was subjected to O2for either 240 or 20 seconds, as shown below in table 5, and the lens was hydrational in deionized water under the following conditions: approximately 7 minutes at a temperature of approximately 22°C, approximately 7 minutes at a temperature of approximately 90°C and approximately 7 minutes at a temperature of approximately 28°C. the Indicated concentration of OSH and MAGH are the total concentrations of the present compounds, including the number of inhibitors that are contained in other components - mPDMS, SiGMA and DMA, and the concentration of OSH and MAGH added directly to the reaction mixture.

Lenses were evaluated on the absorption of proteins after 8 days of daily Incubus is the (method 1) and after 5 days of continuous incubation (method 2). Lenses also investigated the absorption of proteins, as described above. The results are shown in table 5 below.

Table 5
Ave. No.[OSH] (parts per million)[MAGH] (parts per million)[inhibitor](parts per million)O2(C)PU
8 days
(ág/
lens)
PU
5 days
(ág/
lens)
182006008002409,4±0,29,6±0,3
1940060010002408,8±0,28,8±0,3
2060060012002408±0,58,5±0,03
21200110013006,9±0,17,2±0,1
22400110015002406,5±0,26,7±0,1
23600110017002406±0,26,1±0,1
24200160018002405,6±0,45,7±0,4
25400160020002405,7±0,25,7±0,3
26600160022002405,8±0,55,9±0,3
27200600800240 9,2±0,59,3±0,6
282006008002010,6±0,0510,8±0,4
2940016002000207,6±0,17,4±0,2

Between the results of the absorption of proteins, obtained for 8 days (with clearing during the night) and 5 days of continuous incubation, there is no statistically significant difference. Lenses with a high content of MAGH and high content of OSH demonstrated lower overall absorption of proteins. At low concentrations MAGH (600 parts per million) increase in the content of OSH has the effect of reducing the absorption of proteins larger than at high concentrations MAGH (1600 ppm). The increase in total inhibitor content above ~1700 ppm had no significant influence on the overall absorption of proteins.

Examples 26-29

Reactive components and the diluent (tert-amyl alcohol), listed in table 1, and optionally MAGH (at concentrations indicated in table 6) were mixed by stirring or rotation within minicamera 3 hours at a temperature of approximately 23°C until complete dissolution of all components, except that in these examples before adding to the reaction mixture the following components were cleaned up to appropriate concentrations of inhibitor:

mPDMS was cleaned up content [OSH] approximately 100 parts per million;

SiGMA has been cleared to content [MAGH] approximately 100 parts per million. Contents [MAGH] used in DMA was 400 parts per million. Thus, the limiting concentration of inhibitor in the formulation was equal to 500 parts per million. The content of reactive components listed in mass% with respect to all reactive components and diluent in mass percent with respect to the final reaction mixture. To form lenses were subjected to oxygen for approximately 3 minutes at ambient temperature, %O2shown in table 6. Under the N2the reaction mixture was placed in a thermoplastic form for contact lenses (forming the front of the Zeonor®1060R and rear forming from a mixture of 55:45 Zeonor®1060R:polypropylene). The completed forms were then irradiated using lamps TLDK 30W/03 under the following conditions: 1.5 mW/cm2within about 30 seconds at a temperature of approximately 50°C (less than 0.5% O2and about 5 mW/cm2for approximately 4.5 minutes at a temperature close to the part 70°C (less than 3% O 2). Form within 3 seconds, subjected to heat from an infrared heater (Surfaceigniter, LLC, model RC-052), stabilized at a temperature of 800°C and was opened using the lifting pins. The lenses were removed, were extracted and hydrational in deionized water under the following conditions: approximately 7 minutes at 25°C. for approximately 7 minutes at 90°C and about 7 minutes at 20°C.

The lenses were Packed in borate-salt buffer solution in glass vials and sterilized for 20 minutes at 121°C.

The level of absorption of proteins was measured after 6 days as described in comparative example 1 (method 1). The results are shown in table 6.

Table 6
Ave. No.Added [MAGH] parts per millionJust [inhibitor] parts per millionO2, %The specific energy curing,
mW/cm2
The average PU µg/lensWITH*
26150650215241,7
2715065010529the 4.7
28350850215130,5
29350850105172
PU = absorbance of proteins
* = The standard deviation of the rate of absorption of protein (μg/lens)

The results are shown in table 6, clearly show that increasing the concentration of oxygen, which are forms to fill, reduces the absorption of proteins obtained lenses (in example 26, the reduction is 5 µg/lens in comparison with example 27 and example 28, the reduction is 4 µg/lens in comparison with example 29). As can be seen from comparison of example 26 example 28 and example 27 example 29, more than 40% reduction was obtained by increasing the concentration of MAGH from 150 to 350 parts per million.

Examples 30-33

Repeated examples 26-29, except that given to the other energy curing in the second zone was reduced to 0.5 mW/cm 2. The results are shown in table 7 below.

Examples 34-35

Repeated examples 30 and 32, except that the conditions of operations were as follows: 30 minutes in 100% deionized water, 30 minutes in 70% IPA and 30 minutes in 100% deionized water, as shown in table 7, were all carried out at ambient temperature. The results are shown in table 7 below.

Table 7
Ave. No.Flushing[MAGH] parts per millionJust [inhibitor] parts per millionO2, %Energy density, mW/cm2The average PU µg/ lensWITH*
30water150650210,5241,3
31water150650100,5265,2
water350850210,5150,4
33water350850100,5183,6
34IPS150650210,5172
35IPS350850210,5131,6
PU = absorbance of proteins
* = The standard deviation of the rate of absorption of protein (μg/lens)

Examples 36-39

Contact lenses produced as described in comparative example 2, except that mPDMS cleared before adding to the reaction mixture to a concentration of OSH approximately 13 parts per million, and SiGMA and DMA cleanse that is, the total concentration of MAGH in both components was equal to 16 parts per million. In the examples 38-39 were further added OSH and MAGH to get the total concentrations of OSH and MAGH shown in table 8. Forms were subjected to 5% O2within 180 seconds to fill, then the lens utverjdali, took form and was extracted with deionized water, and then extracted from forms as described in example 2. After removal of the forms of lenses closely studied. The output is suitable lenses (without chipping and chipping on the edges) is given in table 8.

Table 8
Ave. No.[OSH]
parts per million
[MAGH]
parts per million
Output (visual control) (% valid)
3613162
3713162
381589320
391589019

Examples 40-44

Contact lenses manufactured as in comparative example 2 (used monomers without treatment with the inhibitor present in the connection from the manufacturer), except that:

forms for 3 minutes was subjected to oxygen concentration specified in table 9 below;

to the effects of heat from the infrared heater of the lens was cooled by a stream of air under pressure (<10°C) (Joule-Thomson) using vortex nozzles (manufactured by ExAir) with coaxial foam insulation Aeroflex;

the lenses were extracted under the following conditions: 100% deionized water for approximately 30 minutes at ambient temperature, a mixture of isopropyl alcohol - deionized water in the ratio of 70:30 for about 30 minutes at ambient temperature and packing solution containing methylcellulose approximately 50 parts per million at ambient temperature for 120 minutes. After removal of the forms of lenses manually checked under a microscope with a 10-fold increase in packing solution containing methylcellulose 50 parts per million. The output is suitable lenses (without chipping and chipping on the edges) is given in table 9.

Table 9
Ave. No.%O2
parts per million
Output (visual control)
(% valid)
40544
417,566
421071
4312,563
441573

Examples 45-53

Reactive components (55% by mass) and the diluent (45% by weight, based on weight percent of the diluent and the final reaction mixture)listed in table 10, were mixed by stirring or rotation for at least 3 hours at a temperature of approximately 23°C until complete dissolution of all components. The content of reactive components listed in mass% with respect to all reactive components. In examples 45, 48 and 51 are indicated the number of MAGH and OSH, which are present in the mixture of monomers without adding additional inhibitor. Additionally OSH and MAGH was added in examples 46-47, 49-50 and 52-53 for more General concentrations of OSH and MAGH, as indicated by the table 10. Under nitrogen, the reaction mixture was placed in a thermoplastic form for contact lenses (front and rear forming material of Zeonor® 1060R set Zeon, Corp.), which was subjected to O2during the night in the concentrations shown in table 11, were irradiated using lamps TLDK 30W/03 under the following conditions: 1,8 mW/cm2for about 25 minutes at a temperature of approximately 65°C and the oxygen content specified in table 11.

Lens manually extracted from forms and washed in 100% deionized water at a temperature of approximately 90°C for from about 20 to 30 minutes. Lenses carried in vessels with packing solution and was placed on a rotating rollers at ambient temperature. After 30 minutes packing the solution was replaced and the vessel was again placed on the rollers additional 30 minutes. The lens was transferred into vials with packing solution and sterilized for 20 minutes at 121°C.

The absorbance of proteins was measured after 7 days as described in comparative example 1 (method 1). The results are shown in table 11.

Table 10
ComponentAve. 45-50 (%)Ave. 51-53 (%)
Norbloc2,22,2
Irgacure 8190,250,25
GAME88
DMA19,5319,53
OH-mPDMS5555
TEGDMA33
Blue GAME0,020,02
PVP K901212
TPGME100%55%
Cekanova acid0%45%

1. The way to reduce the absorption of proteins silicone hydrogel contact lens, comprising adding an effective amount for reducing the absorption of proteins, at least one reducing the absorption of protein compounds in the reaction is ionic mixture; curing the above-mentioned mixture in the form for forming contact lenses and removing the lens from the mold with at least one aqueous solution.

2. The method according to claim 1, in which the specified reduce the absorption of proteins compound selected from the group consisting of inhibitors, regulators, polymerization degree, acceptors radicals, controlled sources of free radicals and mixtures thereof.

3. The method according to claim 2, in which the specified reduce the absorption of proteins compound contains at least one inhibitor.

4. The method according to claim 3, wherein said at least one inhibitor selected from the group consisting of quinones, substituted phenols, arylamino, nitro compounds, oxygen and mixtures thereof.

5. The method according to claim 3, wherein said at least one inhibitor selected from the group consisting of butylhydroxytoluene, nanometrology ether of hydroquinone, O2vitamin E, a mixture of nitric oxide/nitrogen dioxide and mixtures thereof.

6. The method according to claim 3, in which the specified reduce the absorption of proteins compound contains at least one inhibitor selected from the group consisting of butylhydroxytoluene, nanometrology ether of hydroquinone, O2and mixtures thereof.

7. The method according to claim 1, in which the specified contact lens has no cover.

8. The method according to claim 1, wherein the specified at least one reducing the absorption of protein soy is inania is present in the lens in amount less than the amount that causes eye discomfort.

9. The method according to claim 1, wherein the specified at least one reducing the absorption of proteins compound is present in the specified reaction mixture in a concentration of from about 600 million-1up to 2% by weight relative to the reaction mixture.

10. The method according to claim 1, wherein the specified at least one reducing the absorption of proteins compound is present in the specified reaction mixture in a concentration of from about 800 million-1up to 1% by weight relative to the reaction mixture.

11. The method according to claim 1, wherein the specified at least one reducing the absorption of proteins compound is present in the specified reaction mixture in a concentration of from about 1500 to 5000 million-1with respect to the reaction mixture.

12. The method according to claim 1, wherein said method additionally includes the influence of oxygen on the form before downloading the reaction mixture in the form.

13. The method according to item 12, in which the form is exposed to oxygen with a concentration of up to 20% O2during the exposure time of at least 1 min

14. The method according to claim 1, wherein said aqueous solution contains at least 50% by weight of water.

15. The method according to claim 1, wherein said aqueous solution contains at least 70% by weight of water.

16. The method according to claim 1, wherein the silicone-hydrogel is th contact lens demonstrates the decrease in the absorption of protein by at least 10% of at least one protein from letpadaung fluid in comparison with a lens with a smaller, than the specified effective amount of at least one reducing the absorption of proteins connections.

17. The method according to item 16, wherein said at least one protein is denatured protein.

18. The method according to item 16, wherein said at least one protein is different from lactoferrin and lysozyme.

19. The method according to clause 16, in which the aforementioned decrease in the absorption of proteins is at least 20%.

20. The method according to clause 16, in which the absorption of all the proteins is reduced by at least 10%.

21. The method according to claim 1, in which the specified contact lens demonstrates the overall absorption of proteins less than 15 μg per 1 lens.

22. The method according to claim 1, in which the specified contact lens demonstrates the overall absorption of proteins less than 10 μg per 1 lens.

23. The method includes the following stages:
curing the silicone hydrogel reaction mixture containing from 600 to 20000 million-1at least one reduces the absorption of protein compounds in relation to all components of the reaction mixture for the formation of contact lenses;
contacting the specified contact lens with an aqueous solution, with virtually no volatile organic solvents, to reduce the concentration of impurities in the specified contact lens to the level lower than the concentration that causes eye discomfort.



 

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FIELD: physics.

SUBSTANCE: method is realised using lens pairs that act synergistically, each having an optical power profile different from that of the other lenses, wherein each lens has characteristics described in the claim.

EFFECT: design of contact lenses which enable to correct presbyopia, provide good binocularity and enhance vision sharpness at small, medium and long distances.

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5 cl, 4 dwg

FIELD: physics.

SUBSTANCE: method of designing an ophthalmic lens according to the invention involves acquiring original wavefront aberration data for an eye of an individual having a first diameter; extrapolating the aberration data to second diameter and applying a mathematical filter to each meridian of the extrapolated aberration data to reduce excessive variations in thickness of a lens surface. The second diameter substantially corresponds to or is greater than the diameter of an optical zone of a contact lens, and the filter is selected from a group consisting of a Hamming window, a Hanning window, a Parzen window, a Blackman window, and a Welch window.

EFFECT: designing contact lenses which can be used to correct low and high order ocular wavefront aberrations and in which excessive variation of lens thickness is minimised.

8 cl

FIELD: medicine.

SUBSTANCE: group of inventions relates to medical equipment. In generation of setting guide pre-surgical biometrical information, associated with eye, in which implanted intraocular lens (IOL) is to be installed, is collected, and optical power of torus lens and direction of torus lens axis in eye are calculated. Said information represents information for obtaining eye image, measurement of corneal topography for obtaining steep axis, from which direction of torus lens axis is calculated, and obtained from input data, applied for determination of eye center. Said information is transmitted to program of IOL calculation, position and direction of IOL in eye are calculated and generated is setting guide, which contains eye image, obtained during preoperational tests and on which surgeon can depend during IOL implantation operation to determine cut position and proper centering and orientation of IOL. Console of crystalline lens removal contains input port for reception of said information, module of processing and connected with it memory unit, connected to input port. Module of procession is made with possibility to carry out program of IOL calculation, made with possibility of calculating position and orientation of IOL in eye and generating setting guide.

EFFECT: application of group of inventions makes it possible to increase accuracy of placement and orientation of IOL in eye due to provision of feedback during operation, based on pre-operation eye images.

12 cl, 7 dwg

FIELD: physics.

SUBSTANCE: method of making contact lenses includes a step of feeding a liquid composition into a mould designed to make contact lenses, wherein, according to the invention, the liquid composition contains a lens-forming material and a phospholipid, wherein the lens-forming material is cross-linkable and/or a polymerisable with actinic radiation or by heating. Said method also includes a step of cross-linking/polymerising the lens-forming material in the mould to form a lens having a polymer matrix, where at least a portion of the phospholipid moves to the phase boundary between the mould and the polymer matrix of the formed lens, and a step of separating the mould, where the phospholipid is contained in an amount which is sufficient to reduce the averaged force of separating the mould by at least 40% compared to a case when there are no phospholipids.

EFFECT: making contact lenses while ensuring high quality thereof and high output, which is provided owing to easy separation of the mould and extraction of lenses from the mould during injection moulding thereof.

23 cl

FIELD: physics.

SUBSTANCE: contact lens according to the invention consists of an optical zone, a lens periphery, a first and a second thickened zone on the lens periphery, wherein the first and second thickened zones lie asymmetrically about each other, wherein the thickness of each of the thickened zones linearly or nonlinearly increases, starting from the upper part of the zone to the maximum value, and then linearly or nonlinearly falls towards the lower part of the zone.

EFFECT: design of contact lenses which are better held in the required position on the eye compared to traditional stabilised lenses.

18 cl, 5 dwg

FIELD: medicine.

SUBSTANCE: system represents a lens and a series of lenses wherein optical force is distributed to provide positive addidation in a near sight region which is not so much as that one usually required for near sight accommodation, at the same time providing a negative spherical aberration in a peripheral optical region. Dynamic eye factors of the patient are combined with positive addidation provided by a central optical region of the lens, and effective addidation provided by negative spherical aberration provided by the peripheral optical region of the lens for ensuring minimally visible degree of fogging preset for maximal increase of patient's eye focus depth.

EFFECT: creation of the lens and the series of lenses for treating presbyopia and pre-presbyopia not deteriorating intermediate and far vision of the patient

22 cl, 7 dwg

FIELD: physics.

SUBSTANCE: in the method, light is passed through a diffraction lens to an array of elementary lenses, wherein each elementary lens receives a portion of light and the diffraction lens has a zonal boundary covering at least part of one elementary lens. Properties of the diffraction lens are measured based on light focused by the array of elementary lenses and picked up by a detector. The measurement result is adjusted in order to compensate for the assumed optical properties of the diffraction component of the lens in the measuring system. Fuzzy spots and/or double spots can represent diffraction zones of the wave front. The centroid of the spot or the brighter of the two spots can be used to determine the transverse position of the spot. Theoretical calculations, laboratory measurements, clinical measurements and experimental images of the spots can be generated, compared and mutually checked to determine the equivalent single-focus lens.

EFFECT: using diffraction lenses to compensate for optical effects arising due to that the wave front is not smooth and continuous, and local slopes of individual zones and discontinuity on diffraction steps affect the position of the spot.

16 cl, 19 dwg

FIELD: medicine.

SUBSTANCE: invention refers to ophthalmology. According to one of versions, an ophthalmological lens comprises optics having two optical elements arranged sequentially along an optical axis with at least one of said elements laterally movable with respect to the other longitudinal direction substantially perpendicular to said optical axis. There are also at least two haptic elements coupled with each said optical elements, a number of flexible hinges coupling two said haptic elements so that the flexible hinges are laterally movable with respect to each other under action of ciliary muscles causing lateral motion of said optical elements with respect to each other with said elements configured so that said lateral motion causes optical force variation provided by said optics, as well as to spherical aberration presented by said optics.

EFFECT: higher optical properties of the ophthalmological lenses.

15 cl, 3 dwg

FIELD: physics.

SUBSTANCE: design of contact lenses which are useful for preventing myopia and avoid discomfort when corneal shape changes, as well as undesirable side effects during medication, which is ensured owing to that the lens, according to one of its versions, has an optical zone comprising a central zone having an essentially constant distant vision focal power, a first circular zone which is concentric with the central zone and has positive longitudinal spherical aberration, and a second circular zone which is concentric with the first circular zone.

EFFECT: preventing development of myopia.

16 cl, 2 dwg

Optical monocrystal // 2495459

FIELD: physics.

SUBSTANCE: monocrystals are designed for infrared equipment and for making, by extrusion, single- and multi-mode infrared light guides for the spectral range from 2 mcm to 50 mcm, wherein a nanocrystalline structure of infrared light guides with grain size from 30 nm to 100 nm is formed, which determines their functional properties. The monocrystal is made from silver bromide and a solid solution of a bromide and iodide of univalent thallium (TIBr0.46I0.54), with the following ratio of components in wt %: silver bromide 99.5-65.0; solid solution TIBr0.46I0.54 0.5-35.0.

EFFECT: reproducibility and predictability of properties, avoiding cleavage effect, resistance to radioactive, ultraviolet, visible and infrared radiation.

FIELD: measurement equipment.

SUBSTANCE: method involves shaping of a reflector based on organic plastic material and non-organic substance with reflection coefficient of not less than 0.9 by preparing a mixture of initial components under pressure. As organic plastic material there used is a mixture of fluorine and polycarbonate; as non-organic substance - titanium dioxide, at the following component ratio, wt %: polycarbonate 100; fluorine 3.5-5.0; titanium dioxide 0.5-1.0. Forming can be performed by pressing at pressure of 800 to 1500 atm and at temperature of 240-270°C to thickness of not less than 2 mm or by casting at pressure of 750 to 1500 atm and at temperature of 280-290°C to thickness of at least 2 mm. Polycarbonate with melt flow-behaviour index of 2-60 g/10 min can be used as polymer material.

EFFECT: enlarging processing methods, temperature interval of processing, reducing cost and material consumption.

4 cl, 1 dwg

FIELD: physics.

SUBSTANCE: antireflection film has on its surface a moth eye structure which includes a plurality of convex portions, wherein the width between the peaks of adjacent convex portions does not exceed the wavelength of visible light. The moth eye structure includes a sticky structure formed by connecting top ends of the convex portions to each other and the diameter of the sticky structure is smaller than 0.3 mcm. The aspect ratio of each of the plurality of convex portions is less than 1.0, and the height of each of the plurality of convex portions is shorter than 200 nm.

EFFECT: reduced light scattering.

29 cl, 69 dwg

FIELD: chemistry.

SUBSTANCE: germanium monocrystals are grown in crystallographic direction [111] after holding at melting point for 1-2 hours, with temperature gradient at the crystallisation front in the range of (10.0÷18.0) K/cm, which provides dislocation density on the level of (2·104-5·105) per cm2.

EFFECT: invention enables to obtain germanium monocrystals with considerable increase in signal reception area due to directed introduction of a given concentration of dislocations into the grown crystal and conversion of said dislocations from standard crystal defects to active elements of infrared optical devices.

3 dwg, 1 tbl

FIELD: physics.

SUBSTANCE: antireflection film has, on its surface, a moth-eye structure including a plurality of convex portions such that a width between vertices of adjacent convex portions is not greater than a wavelength of visible light, wherein the moth-eye structure includes a sticking structure formed when tip end portions of the convex portions are joined to each other. The diameter of the sticking structure is greater than or equal to 0.3 mcm and density of the number of sticking structures per unit area of the plane of the antireflection film is lower than 2.1 units/mcm2.

EFFECT: reduced light scattering.

29 cl, 69 dwg

Contact lenses // 2486920

FIELD: medicine.

SUBSTANCE: invention refers to an ophthalmic product represented by a sealed and sterilised package comprising a packaging solution and a soft hydrogel contact lens immersed in the packaging solution. The soft hydrogel contact lens comprises a polymer matrix, a first leaching polymeric lubricant and a second leaching polymeric lubricant, wherein the second leaching polymeric lubricant has an average molecular weight at least 3 times greater than the average molecular weight of the first leaching polymeric lubricant. The packaging solution contains approximately 0.1 wt % to approximately 1 wt % of a hydroxyl-containing polymer increasing the viscosity and specified in the group consisting of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and mixtures thereof, polyethylene glycol having a molecular weight of 400 or less, α-oxo-polyatomic acid or a salt thereof in an amount sufficient to provide a reduced oxidative degradability of polyethylene glycol in the packaging solution with the viscosity from approximately 2.0 to approximately 8.0 cps at 25°C, one or more buffer agents in an amount sufficient to provide a pH of the solution equal to 6.0 to 8.0, and wherein the packaging solution has an osmolality from approximately 200 to approximately 450 mOsm/kg. What is also described is a method for producing the soft contact lens.

EFFECT: helping with the initial discomfort of an individual who wears the contact lenses and comforting the above individual for a period of time longer than 6 h.

15 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: method involves loading starting separate silver chloride and silver bromide salts into a container made of heat-resistant glass, fusing said salts to a given composition of solid solution, growing a monocrystal in a halogenating atmosphere by moving the container in a temperature gradient, cooling the grown crystal to room temperature and removing the crystal from the container; the monocrystal is then heated at a rate of 50-60°C per hour to temperature of 250-270°C, held at said temperature for 1-2 hours, cooled at a rate of 20-25°C per hour to temperature of 100-150°C and then cooled at a rate of 30-40°C per hour to room temperature.

EFFECT: reduced internal stress in the crystalline workpiece, improved optical homogeneity and reduced optical losses.

2 ex

FIELD: physics.

SUBSTANCE: flat lens made from leucosapphire is made from a plastically deformed workpiece, wherein the axis of symmetry of the flat lens coincides with the height of the cone of optical axes of the plastically deformed workpiece. The entrance and exit surfaces are flat and perpendicular to the axis of symmetry. The method of making the flat lens involves making a concave-convex workpiece by plastic deformation - bending the plane-parallel plate from the Z crystal cut. The lens is formed by removing an excess layer of material from the workpiece as a plane-parallel plate, perpendicular to the axis of symmetry of the workpiece, which is superposed with the axis of the cone of optical axes, of a given thickness. The entrance surface of the flat lens lies at a distance x<δ from the vertex of the workpiece, where δ is the thickness of the workpiece.

EFFECT: forming a flat converging lens from leucosapphire for extraordinary beams.

2 cl, 2 dwg

FIELD: metallurgy.

SUBSTANCE: mould for formation of a moth eye structure on the surface comprises a base from glass or plastic, an inorganic sublayer, a buffer layer, containing aluminium, an aluminium layer and a porous layer of aluminium oxide, having on the surface a tilted structure of moth eye with multiple grooves, the size of which in two dimensions visible in direction of the normal line to the surface makes at least 10 nm and less than 500 nm. The method includes the following stages: (a) the mould base is provided from glass or plastic, an inorganic sublayer, a buffer layer, containing aluminium, and an aluminium layer, (b) the aluminium layer is partially anodised for formation of the porous layer of aluminium oxide with multiple grooves, (c) the porous layer of aluminium oxide is exposed to etching, increasing grooves in the porous layer in size, and (d) the porous layer of aluminium oxide is anodised for growth of grooves.

EFFECT: increased adhesion between an aluminium layer and a base.

8 cl, 2 tbl, 4 ex, 7 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to opto- and microelectronics and can be used to make opal-like structures. The method of producing photonic-crystal structures based on metal oxide materials involves filling a template consisting of monodispersed micropheres of polystyrene, solutions of metal-containing precursors, followed by annealing the structure on air at temperature of 450-550°C for 8-10 hours. The precursors from which the structure is formed are saturated alcohol solutions of tin dichloride SnCl2·2H2O or zinc nitrate Zn(NO3)2·2H2O.

EFFECT: invention enables to obtain photonic-crystal structures based on SnO2 and ZnO with a photonic stop band in the visible or near infrared spectral range and porosity of not less than 85%.

5 dwg

FIELD: process engineering.

SUBSTANCE: proposed method comprises the stages that follow. Single substrate with optical quality zone is brought in contact with reactive mix to transmit actinic radiation through said single substrate so that portion of said reactive mix is polymerised and ocular lens workpiece is formed. Transmission of said actinic radiation is controlled by voxels. Ocular lens workpiece comprises first and second surface sections in optical quality zone, second section being formed in free manner. Proposed method comprises the stages that follow. Ocular lens workpiece is formed with first and second surfaces by irradiating reactive mix with first actinic radiation transmitted through the substrate. Note here that transmission of said actinic radiation is controlled by voxels to spread first portion of fluid over second surface and to irradiate lens workpiece with second actinic radiation.

EFFECT: lens with preset sizes and geometry.

39 cl, 19 dwg, 3 tbl, 2 ex

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