MXPA01003611A - Injectable intraocular lens - Google Patents

Abstract

The present invention relates to polysiloxanes suitable for the preparation of intraocular lenses by a cross-linking reaction, having a specific gravity of greater than about 1.0, a refractive index suitable for restoring the refractive power of the natural crystalline lens and a viscosity suitable for injection through a standard cannula. The present invention includes an injectable intraocular lens material based on said polysiloxanes and methods of preparing intraocular lenses by direct injection into the capsular bag of the eye.

Description

INJECTABLE INTRAOCULAR LENS Field of the Invention The present invention relates to an intraocular lens and to materials useful in the preparation of intraocular lenses (IOLs), specifically, injectable IOLs and methods for their preparation. More particularly, the present invention relates to silicone materials of higher specific gravity suitable for making flexible IOLs, which can be injected into the capsular bag with greater convenience than the materials suggested above.

Antecedents of the Invention. The human eye is a highly developed and complex sensory organ. It is composed of a cornea, or clear outer tissue which refracts the rays of light and routes them towards the pupil, an iris that controls the size of the pupil, thus regulating the amount of light that enters the eye, and a lens which focuses the light that enters through the vitreous fluid to the retina. The retina converts the light that enters into electrical energy which is transmitted through the brain stem to the occipital cortex resulting in a visual image. In a perfect eye, the path of light from the cornea, which passes through the lens and vitreous fluid to the retina, is not obstructed. Any obstruction or loss in clarity, within these structures causes scattering or absorption of light rays resulting in decreased visual acuity. For example, the cornea may be damaged resulting in edema, scarring or abrasion, the lens is susceptible to oxidative damage, trauma and infection, and the vitreous fluid may become cloudy due to hemorrhage or inflammation.

As the body ages, the effects of oxidative damage caused by exposure to the environment and production of accumulated endogenous free radicals, results in a loss of lens flexibility and denatured proteins that coagulate slowly reducing lens transparency. The natural flexibility of the lens is essential to focus light on the retina through a process referred to as flexibilization. Flexibility allows the eye to automatically adjust the field of view of objects at different distances. A common condition known as presbyopia results when the cumulative effects of oxidative damage decrease this flexibility, reducing the acuity of near vision. Presbyopia usually begins to appear in adults during the middle of its fourth decade of age; mild forms are treated with glasses or contact lenses. Lenticular cataract is a lens disorder that results from excessive development of coagulated protein and calcification. There are four common types of cataracts: senile cataracts, associated with aging and oxidative stress, traumatic cataracts which develop after a foreign body enters the lens capsule or after intense exposure to ionization or infrared radiation, complicated cataracts which are subsequent to diseases, such as diabetes mellitus or eye disorders such as detached retinas, glaucoma and retinitis pigmentosa, and toxic cataracts resulting from medicinal or chemical intoxication. Regardless of the cause, the disease results in impaired vision and can lead to blindness. Treatment of severe lens disease requires surgical removal of the lens, which involves phacoemulsification followed by irrigation and aspiration. However, without a lens, the eye does not have the ability to focus the light that enters the retina. Consistently, an artificial lens is used to restore vision. Three types of lens prostheses are available: cataract eyeglasses, external contact lenses and IOLs. Cataract glasses have thick lenses, are unpleasantly heavy and cause distortion of vision, such as magnification of the central image and distortion of lateral vision. Contact lenses solve much of the problems associated with glasses, but require frequent cleaning, are difficult to handle (especially for elderly patients with arthritis symptoms), and are not suitable for people who have limited tear production. Intraocular lenses are used in most cases to overcome the aforementioned difficulties associated with cataract and contact lenses.

The IOLs mentioned in the prior art documentation, usually belong to one of the following categories: non-deformable, can be doubled, are expandable and injectable hydrogels. The previous IOLs, which enter the practice of surgery, are non-deformable implants that have rigid structures composed of acrylates and methacrylates. These types of lenses require a large surgical incision in the capsular bag and are not flexible. The large incision results in prolonged recovery times and the likelihood of introducing astigmatism. In an effort to reduce recovery time and patient discomfort, numerous techniques and lenses with small incisions have been developed. The current IOLs, designed for implantation with a small incision, have elastomeric characteristics and are made of silicone materials. This type of lens can be rolled or folded, inserted into the capsular bag, and once inside, it can be unfolded. Occasionally, bending the lens prior to insertion results in permanent deformation that adversely affects the optical qualities of the implant. The bending lenses meet the requirement to reduce the large size of the required surgical incision of non-deformable lenses, but they are not flexible. In addition, IOLs are both non-deformable and can bend, are susceptible to mechanical dislocation resulting in damage to the corneal endothelium.

It has been further suggested to use an elastomeric polymer that becomes flexible when heated at body temperature or slightly up, in an IOL implantation with small incision. Once flexible, said lens could be deformed along at least one axis, reducing its size enough to facilitate insertion through a small incision. Subsequently, the lens is cooled to retain the modified form until it is reheated. The cooled lens is inserted into the capsular bag and the natural temperature of the body tempers the lens and it returns to its original shape. The main drawback of the thermoplastic lens is the limited number of polymers that exactly meet the needs of this method. Most polymers are composed of polymethylacrylate which has solid-liquid transition temperatures above 100 ° C. To reduce these transition temperatures, modifications to the temperatures of the polymer substrate are required with the use of plasticizers, which can eventually be filtered inside the eye.

Dehydrated hydrogels have also been suggested for techniques with small incisions. The hydrogel lenses are dehydrated before insertion and rehydrated naturally once they are inside the capsular bag. However, once the polymer structure is completely hydrated it becomes noticeably weak due to the large amount of water absorbed. The typical diameter of the dehydrated hydrogel will expand from 3 mm to ß mm resulting in a lens containing approximately 85% water. At this concentration of water, the refractive index falls to approximately 1.36, which is unacceptable for an IOL. To achieve a refractive index equal to or greater than that of the natural lens (> 1.40), a significantly thicker lens is required; This is emphasized when the diameters exceed 6 mm.

To further develop the IOLs and reduce the size of the surgical incisions to less than 1.5 mm, techniques with injectable IOLs have been suggested, where the low viscosity lens material is injected directly into the empty capsular bag and is cured in situ, as part of the surgical procedure. In this process, the capsular bag will be used as a mold to form the lens shape, and thus contribute to controlling its refraction. Several attempts have been made to develop materials suitable for use as injectable IOLs. For example, in its patents Nos. 5,278,258, 5,391,590 (? 590) and 5,411,553, Gerace et al. disclose a rapid cure mixture of polyorganosiloxane containing vinyl, organosilicone comprising hydride groups and a platinum group metal catalyst used to form an IOL. The resulting polymers showed a reduced tendency to discoloration, compared to other silicone polymers catalyzed by platinum. The '590 patent also discloses a substantially non-functional component of the polymer blend having a viscosity of at least 50 times greater than the functional polymers. The non-functional component is mixed with the functional components to adjust the viscosity to a previously determined specification. In U.S. Patent No. 5,476,515, Kelman describes an IOL of injectable collagen. This lens is clear, resistant to epithelialization and has the ability to flex. Said lens is made of a transparent collagen compound having a refractive index range of from 1.2 to 1.6 which can be used either in its original viscous state, or polymerized in a soft gel. The collagen compound is injected directly into the capsular bag after removal of the natural lens.

In addition to the problems with gaining control over the crosslinking process and finding clinically acceptable conditions, there is an effort to refine the polyorganosiloxane compositions, since these need to have a suitable viscosity for injection, a refractive index suitably prone to leak out of the desired injection site (e.g., the capsular bag). This is considered in the aforementioned US Pat. No. 5,391,590, wherein an additional high viscosity polysiloxane is added to the injection mixture. However, high viscosity silicones have the disadvantage that they can trap air bubbles, which can spoil the optical quality of the resulting product. Furthermore, it has been found that polyorganosiloxanes having an upper fraction of dimethylsiloxane units can have an unacceptably low specific gravity with the undesired result that the injected lens material would float in an aqueous layer within the capsular bag. In such a case, it would be difficult to completely fill the capsular bag and the surgeon would be required to manually express the water in order to maintain the correct lens shape during the healing process. Therefore, it is desirable to formulate a material for forming an injectable lens from polysiloxanes, which can overcome the problems with respect to flotation and filtration, while still having an adequately high refractive index and desirable mechanical and optical qualities, to constitute in this way an optimal replacement of the natural lens. These characteristics are achieved through the injectable lens material of the present invention with a specific gravity greater than 1.0, which maintains a sufficiently high refractive index, at least similar to that of natural lenses, and provides a surface of the lenses resulting optically smooth.

Summary of the Invention. The objects of the present invention provide injectable materials useful in the preparation of IOLs, specifically, injectable IOLs, and methods for their preparation and use. In particular, it is an object of the present invention to provide intraocular lenses having the advantage of a specific gravity greater than 1.0, which greatly simplifies the injection of the silicone material to form the lens and helps ensure proper positioning and conformation once cured in situ, while having the ability to provide a controllable refractive index within the physiological range that the recipient requires for adequate vision and a suitably low modulus of the cured product, to better replicate the flexibility characteristics of the implanted lens. A further object is to provide materials and methods that lead to a fully cured injectable IOL with an optically smooth surface. These and other objects not specifically described, are pointed out by identifying the silicone materials of higher specific gravity suitable for the production of flexible IOLs, which can be injected with greater convenience than ordinary materials.

In its most general form, the present invention relates to polysiloxanes suitable for the preparation of intraocular lenses through a crosslinking reaction, having a specific gravity greater than about 1.0, a suitable refractive index to restore the refractive power of the natural crystalline lens and a suitable viscosity for injection through a standard cannula. It will be understood that the polysiloxanes comprise a certain amount of functional unsaturated groups suitable for the reaction with hydride groups bonded by silicone (Si-H) in the presence of a catalyst. Those skilled in the art are aware of a large number of alkenyl portions and different routes of how to synthesize functional vinyl polysiloxanes. A suitable route and commonly used, is to introduce final blocking groups of vinyl dimethyl siloxane, wherein the olefinic vinyl group will have the ability to cure by crosslinking. The polysiloxanes according to the present invention may have refractive index ranges of between 1382 and up to about 1.60, preferably from about 1.38 to 1.46 and more preferably index ranges from about 1.38 to 1.43, in order to be suitable as a material for the production of intraocular lenses. Most preferably, they are the polysiloxanes of the present invention having a specific gravity within the range from about 1.03 to about 1.20. The polysiloxanes must also have a suitable viscosity to be injectable rapidly through a conventional cannula having a 18 gauge needle dimension or finer dimensions. Preferably, the polysiloxanes should have the ability to pass through a Caliber 21 needle. To meet these injection capacity criteria, the polysiloxanes according to the present invention should have a viscosity of less than about 60,000 cSt. More preferably, the viscosity should be less than about 8000 cSt. The expert in the field will have the ability to relate these requirements to suitable polymerization degrees.

The polysiloxanes usually consist essentially of different siloxane monomer units having the general formula -RaRbSiO-, wherein Ra and Rb are the same or different substituted or unsubstituted alkyl or aryl groups bonded to the silicone atom. According to the present invention, at least one of the siloxane monomers included in the polysiloxanes has a specific gravity greater than about 1.0. According to one aspect of the present invention, the polysiloxanes have at least one monomer, wherein Ra and Rb are the same or different alkyl or aryl groups of which at least one of said groups is substituted with one or more atoms of fluorine. Preferably, the polysiloxanes comprise monomer units, wherein Ra is fluoroalkyl and Rb is alkyl, and more preferably the polysiloxanes comprise 3,3,3-trifluoropropylmethylsiloxane monomers. In order to provide the polysiloxanes with the usually higher specific gravity, it is preferable that the fluoroalkyl containing monomers exceed about 4 mol. In addition, it is also preferable that one of the siloxane monomers is an arylsiloxane and it is especially preferred that the arylsiloxanes be diphenylsiloxane and phenylalkylsiloxane.

According to one aspect of the present invention, the polysiloxanes are essentially terpolymers derived from three different siloxane monomers of the general formula (R? R2SiO)? (R3R4SiO) m (R5R6SiO), wherein one of the three monomers has a specific gravity greater than about 1.0 and said terpolymer has a refractive index of about 1.41. In order to achieve polysiloxanes with the aforementioned requirements, in which the inventors have found that they are advantageous to obtain a material suitable to be injected into the capsular bag of the eye, it has been adequately discovered that Ri and R2 are the same or different substituted or unsubstituted lower alkyl and more preferably both are methyl. R3 and R4 must be selected from the same or different substituted or unsubstituted aryl and alkyl groups, preferably R3 is phenyl and R4 is phenyl or methyl. R5 and Re must be selected from fluoroalkyl and alkyl groups, and preferably R5 is trifluoropropyl and Re is methyl. Alternatively, the polysiloxanes of the present invention can be higher polymers than terpolymers, including but not limited to, as mentioned above, tetracopolymers with the same types of monomers. According to a preferred aspect of the present invention, the polysiloxanes are essentially vinyl terminated terpolymers having the formula: wherein R1 and R2 are independently Cr alkyl C 6 f R 'is phenyl, R * is phenyl or Ci-C 6 alkyl R- is CF 3 (CH 2) X wherein x is from 1 to 5; R6 is C? -C6 alkyl or fluoroalkyl; 1 is in the molar fraction range from 0 to 0.95; m is in the molar fraction range from 0 to 0.7; and n is in the molar fraction range from 0 to 0.65. It is preferable that R1 is methyl, that R2 is methyl, R4 is phenyl, that x is 2, either independently or in combination. Preferably, according to these alternatives R6 is methyl. According to one embodiment, the polysiloxane is a copolymer of diphenyl or siloxane phenylalkyl and dialkyl siloxane. According to further embodiments, the polysiloxane is a copolymer of siloxane diphenyl or phenylalkyl and siloxane trifluoroalkyl (alkyl), or a higher terpolymer or polymer of diphenyl siloxane and / or phenylalkyl, dialkyl siloxane and alkyl trifluoroalkyl siloxane. According to a specific preferred embodiment, the polysiloxane is a terpolymer of dimethyl siloxane, diphenyl siloxane or phenylmethyl siloxane and 3,3,3-trifluoropropylmethyl siloxane. Preferably, said polysiloxanes comprise at least about 4 mol% of trifluoropropylmethyl siloxane and from 1 to 50 mol% of diphenylsiloxane and / or phenylmethylsiloxane. More preferablysaid polysiloxanes comprise approximately 4 to 65 milliliters of 3,3,3-trifluoropropylmethyl siloxane, from 1 to 50 mol of diphenylsiloxane monomer units and dimethylsiloxane. A polysiloxane composition suitable to be part of a composition for injection into the capsular bag of the human eye for the formation of IOL, comprises about 28 ol of trifluoropropylmethyl siloxane units, about 4 mol of diphenyl siloxane monomer and dimethyl siloxane units.

An important part of the present invention is the provision of an injectable lens material, comprising polysiloxanes having a specific gravity that is greater than about 1.0 and a refractive index of a natural lens, which are defined above, a crosslinking agent. which has an adequate amount of non-reactivated Si-H groups and a catalyst. It will be understood by those skilled in the art that said material is prepared by mixing the polysiloxane and catalyst formulation with a formulation of the crosslinking agent, just before use. It will also be understood that these formulations may comprise additional conventional constituents, such as agents that affect crosslinking and agents commonly associated with the production of IOLs from silicone materials, for example, UV light absorbers. The catalysts can be found between catalysts containing platinum group metal commonly cooled to catalyze the formation of bonds between Si-H groups and vinyl groups, as referred to in US Pat. No. 5,278,258.

The crosslinking agents are of the siloxane or polysiloxane type (for example, a multifunctional organohydrogenpolysiloxane) which carries at least two, preferably at least three Si-H groups, as described in US Patent Number. 5,278,258 and 5,444,106, whose documents are incorporated as references for the crosslinking process. Other suitable crosslinkers are the branched siloxanes mentioned in U.S. Patent No. 2,877,255. An example of a crosslinking agent particularly suitable for the present invention is silane tetrakis (dimethylsiloxy). The amounts of the components of the injectable material may vary according to specific conditions. For example, it is desirable to have a reasonably rapid healing process at body temperature, such that the final cure is achieved within about 2 to 6 hours and that the injected composition is gelatinized in a stable polymer network within a time of proper operation for the surgeon. The person skilled in the art will have the ability to find the variation of the appropriate amount of the components and to select suitable catalysts and crosslinking agents to obtain a suitable crosslink density, and thus, the resulting lens quality will not be compromised. with no optical deficiency, such as discoloration from excessive catalyst levels. Examples of preferred routes for producing the IOLs of the lens material of the present invention are based on specific polysiloxanes to be provided below.

Preferred higher specific gravity polysiloxanes are prepared from a mixture of siloxane compounds including either higher-order cyclic trimers, tetramers, or siloxanes. Monomers used in the preferred embodiments of the present invention, include but are not limited to methyl and substituted methyl siloxanes, phenyl siloxanes and trifluoropropyl methylsiloxanes having individual specific gravities in the range of between about 0.97 and 1.28. A crosslinkable terpolymer silicone fluid, suitable for an IOL, can be prepared by copolymerizing three or more siloxane monomers in a predetermined ratio. Once the polymer is formed, it has a specific gravity greater than 1.0 and can be injected into the patient's capsular bag previously prepared in a mixture with a cross-linker, the necessary catalyst and inhibitor formulation and can be cured in situ. At the beginning, for example, the gelatinization phase of the healing process, the intraocular pressure is maintained to ensure the positioning and conformation of the suitable lens within the capsular bag. The resulting IOL will have a refractive index within the previously determined physiological range, which is optimal for the given application and for an optically smooth surface.

Detailed Description of the Invention. The types of siloxane monomers useful in the preparation of IOLs of this preferred embodiment include, but are not limited to, methyl and substituted methyl siloxanes, phenyl siloxanes or methyl trifluoropropyl siloxanes with individual specific gravities in the range of 0.97 and 1.28. The silicone copolymers of higher specific gravity of the present invention are prepared by mixing a plurality of these compounds, in a predetermined ratio to achieve a desired specific gravity and refractive index. According to one embodiment, three siloxane monomers are mixed together with a suitable final blocker, and are dried in a reduced atmosphere under controlled thermal conditions. The reaction mixture is subsequently catalyzed to induce copolymerization in an inert atmosphere. The reaction is allowed to continue for a predetermined time in a precise thermal environment, and is subsequently terminated. Then, the reaction product is washed, precipitated and dried. The specific gravity, refractive index and average molecular weight are determined. In another embodiment of the present invention, three siloxane monomers are mixed together with a suitable final blocker and dried in a reduced atmosphere under controlled thermal conditions, as described above. The reaction mixture is subsequently catalyzed to induce copolymerization in an inert atmosphere. The reaction is allowed to continue for a predetermined time in a precise thermal environment, and is subsequently completed. Then, the reaction product is washed, precipitated and dried. The resulting precipitate is subsequently dissolved again in a suitable solvent and filtered to improve clarity. The specific gravity, refractive index and average molecular weight are determined. The changes in the reactants, their relative concentrations and their reaction conditions, will result in a variety of final products with specific gravities and different refractive indices. The benefits of these differences will be appreciated by an expert in the field from the specific examples that follow.

According to the methods of the present invention, the proportion of siloxane monomer reagents needed to achieve a desired refractive index and specific gravity can be mathematically approximated. If N is the desired IOL 's refractive index and P is the specific gravity of the lens copolymer, and where n1-3 are the refractive indices and p? -3 are the specific gravities of the monomer reagents, then the following mathematical relationship: N = x? N? + x2n2 + x3n3 P = ipi + x2p2 + x3p3 Where X1-3 represents the proportion of the reagents of the individual siloxane monomer required to achieve an IOL with the desired optical and physical properties and xi + x + x3 = 1. Having an injectable silicone lens with a specific gravity greater than 1.0 , the injection process will be considerably simplified and this represents a significant improvement over the materials previously suggested for injectable lens materials. Prosthetic lenses made through the process described here, are manageable and retain the refractive index of the natural lens making them ideal as corrective lenses, as well as replacements for damaged or cataract lenses. The present invention considerably improves the materials for injectable IOLs based on polysiloxanes preferred above, due to its specific gravity increased to above 1.0, in such a way that the remaining water is displaced after its injection in the aqueous environment of the capsular bag . This feature will reduce the post-injection manipulation of the surgeon and will ensure that the lens will assume a position and configuration distributed in a considerable way so that it is possible to adjust the refractive result of the injected lens formed with the capsular bag as a mold, having fractions of suitable siloxane units that contribute to a higher refractive index and siloxane units that contribute to higher density. Another advantage of the present invention is that extremely curable natural fully cured lenses can be obtained. If a conventional bending silicone lens is considered to have a stiffness of 100, a cured injectable lens made from the material of the present invention could be designed to have a stiffness range from zero to five. Therefore, lenses made from the material described here can be flexible and respond naturally to changes in the shape of the eyes, since the focus length is adjusted. The flexible nature of the lenses made of the materials of the present invention, could make them particularly suitable for corrective purposes in addition to replacements for affected natural lenses, and is considered within the scope of the present invention. An unexpected and beneficial advantage of the present invention is that the optically smooth surface formed after the lens is cured in situ. The examples that follow are provided by way of illustration of the principles of the present invention, and not as a limitation.

Example 1 Preparation of poly (dimethyl-co-methylphenyl-co-trifluoropropylmethyl) siloxane To a dry 50 ml flask was added siloxane monomers: hexamethylcyclotrisiloxane, 6.0g, 3,3,3-trifluoropropylmethylcyclotrisiloxane, 7.3g, 1.3, 5-trimethyl-1, 3,5-triphenylcyclotrisiloxane, 1.7g (1.55ml), and a final blocker, 1,3-divinyltetramethyldisiloxane, 0.14g (0.17ml). The mixture was dried under vacuum at a temperature of 80 ° C for 30 minutes, then purged with argon. The temperature was raised to 140 ° C and 7 mg of potassium silanolate catalyst was added to initiate the polymerization. The reaction proceeded rapidly as indicated, by an increase in viscosity. After about 30 minutes the mixture was clarified. After about 3 hours the temperature was raised to 160 ° C and the reaction continued for an additional 3 hours, after which the reaction was cooled to room temperature. The polymer was cleaned using a procedure of dilution with tetrahydrofuran and precipitation in methanol, then it was dried. The dried silicone product was a clear glass, with refractive index: 1.4070 (calculated: 1.410), specific gravity: 1116 (calculated: 1.104), and molecular weight by GPC 25,000. The crosslinking of the polymer produced a clear silicone gel: Example 2 Preparation of poly (dimethyl-co-methylphenyl-co-trifluoropropylmethyl) siloxane A reaction mixture was prepared according to Example 1, except that the siloxane monomers were hexamethylcyclotrisiloxane, 9.0g, 3,3,3-trifluoropropylmethylcyclotrisiloxane, 4.65g, 1,3,5-trimethyl-1,3,5- Triphenylcyclotrisiloxane, 1.35g (1.23ml). The resulting silicone polymer product was a clear glass, the refractive index was 1.4082 (calculated: 1.410), specific gravity of 1.066 (calculated: 1.056) and the molecular weight by GPC was 26,000.

Example 3 Preparation of poly (dimethyl-co-diphenyl-co-trifluoropropylmethyl) siloxane To a dry 50 ml flask were added siloxane monomers: hexamethylcyclotrisiloxane, 7.5g, 3,3,3-trifluoropropylmethylcyclotrisiloxane, 6.66g, hexaphenylcyclotrisiloxane, 1.68g. , and a final blocker, 1,3-divinyltetramethyldisiloxane, 0.28g (0.34ml). The mixture was dried under vacuum at a temperature of 80 ° C for 30 minutes, then purged with argon. The temperature was raised to 140 ° C and a potassium silanolate catalyst, approximately 7 mg, was added to initiate the polymerization. The reaction proceeded rapidly as indicated, by an increase in viscosity. After about 30 minutes, the solution was almost clear, with some residue in the bottom part of the reaction vessel. The viscosity of the reaction mixture decreased. After about 2 hours, the temperature was raised to 160 ° C and the reaction continued for an additional 3 hours, after which the reaction was cooled to room temperature. The polymer was washed with tetrahydrofuran and precipitated in methanol, then dried. The dry silicone product was slightly cloudy. The material was dissolved in tetrahydrofuran, filtered through a 0.45 micron filter, and dried again, producing a clear glass silicone polymer. The refractive index was 1.4095 (calculated: 1424), specific gravity of 1.10 (calculated: 1.094) and the molecular weight by GPC was 18,000. The crosslinking of this material produced a clear silicone gel.

Example 4 Preparation of poly (dimethyl-co-diphenyl-co-tri-looropropylmethyl) siloxane To a dry 100-ml flask was charged in order: octaphenylcyclotetrasiloxane, 90.61g, 3,3,3-trifluoropropylmethylcyclotrisiloxane, 101.88g, octamethylcyclotetrasiloxane, 368.27 g, and a final oligomer blocker dimethylsiloxane α, α-di vinyl (Mn 1287 by NMR analysis), 40.93g. The flask was equipped for reflux and the reagents were dried under vacuum in a bath at a temperature of 80 ° C for 30 minutes. The system was purged with nitrogen, and potassium silanolate (Mn 395), 267mg was added. The bath temperature was increased to 160 ° C and the mixture was heated and stirred for 20 hours, yielding a clear colorless polymer mixture. After cooling, the product was diluted with 420ml of dichloromethane, and washed four times with 420ml portions of water, the first portion being acidified with 3. Oml of 0.1N HCl, and the second portion with 0. ßml 0. IN HCl (the third and fourth portions were not acidified). Subsequently, the polymer was washed twice with 420 ml portions of methanol, diluted with 180 ml of tetrahydrofuran and washed twice more with methanol, as indicated above. Subsequently the solvent was removed under vacuum for a few hours, heating it in a bath at a temperature of 100 ° C, at a low pressure of lmbar. The polysiloxane product was clear and colorless, with a refractive index of 1428 (calculated: 1.432) and a density of 1.04 (calculated: 1.043). The viscosity at a temperature of 25 ° C was 1802 cP. H-NMR, 500MHz, produced unit mole ratios: dimethyl / diphenyl / trifluoropropylo / divinyltetra methyl of 0.819 / 0.071 / 0.105 / 0.00494 (the monomer ratios were: 0.827 / 0.070 / 0.099 / 0.00483), implying Mn 18,600. The GPC produced Mn 18,500 and Mw 36,600.

Example 5 Preparation of poly (dimethyl-co-diphenyl-co-tri-looropropylmethyl) siloxane. The polymerization method of Example 3 was repeated on a reagent scale of 125 g, employing octaphenyl tertiarytrasiloxane, 34.88 g, 3,3,3-trifluoropropylmethylcyclotrisiloxane, 25.25 g, octamethylcyclotetrasiloxane, 56.4 g, and a final dimethylsiloxane oligomer, α-? di vinyl (Mn 1287), 8.50g, and potassium silanolate, 55mg. The preparation was different from that of Example 3, using 57ml chloroform, to dilute the polymer followed by three washes with water and two with methanol, all portions were 88ml, then the dilution with 44ml of tetrahydrofuran, followed by two more washes with portions of 88ml of methanol, then the vacuum separation was done to < lmbar in a bath at a temperature of 100 ° C. The clear colorless product had a refractive index of 1. 455 (calculated: 1,460) and density of 1.08 (calculated: 1.080). The viscosity at a temperature of 25 ° C was 3324 cP. H-NMR, 500MHz, produced proportions of moles of units: dimethyl / diphenyl / trifluoropropyl / divinyltetramethyl of 0.697 / 0.158 / 0.140 / 0.00570 (monomer ratios were: 0.713 / 0.146 / 0.135 / 0.00549), implying Mn 18,600. The GPC produced Mn 16,900 and Mw 33,400.

EXAMPLE 6 Curing of Prepolymers The silicone polymers were prepared for curing by formulating two parts, a Part A containing a platinum catalyst in the form of the 1,3-divinyltetramethyldisiloxane complex, and a part B containing a crosslinker and an inhibitor. siloxane. The preferred crosslinker was tetrakisdimethylsiloxysilane, TKDMSS, although it is also reported in the present invention for comparison a polymeric silicon hydride (Gelest / ABCR HMS-151, a copolymer of methylhydrosiloxane and di-ethylsiloxane having Mn 1900-2000 and 15-18moll units MeHSiO). The optimal proportions of catalyst, crosslinker and inhibitor were determined, studying the cure profiles of the silicone mixtures using a rheometer (Rheometrics RDA 2, with the determination of the modulus of the cured materials). The mixtures were formulated to produce gel times approximately 15-20 minutes at a temperature of 20 ° C. Tests were carried out at a temperature of 35 ° C using plates of 25mm diameter with 1mm spacing. Frequency and deformation sweeps in the materials were carried out regularly. The mixtures for the elaboration of tests were prepared by weighing in exact portions of Parts A and B, mixing for 2 minutes, and extracting the gases under reduced pressure before transferring the mixture to the plates. The discs obtained from the mixtures were clear and colorless. The results obtained are illustrated in the examples that follow: Example 6 (a).

The prepolymer prepared in Example 4 was formulated as Part A, containing approximately 8ppm of platinum, and Part B containing 18.2mg TKDMSS / g Part B, in addition to siloxane inhibitor. The mixture was analyzed in the rheometer in different proportions of weight of B / A at a temperature of 35 ° C, determining the modulus of cut, G ', after 3000 seconds, time in which the mixtures were completely cured. The results of the proportions B / A were: proportion: 0.86, G '199.2 kPa; proportion: 1.00: G '217.2 kPa; proportion: 1.15, G '214.5 kPa.

Example 6 (b). The prepolymer prepared as in Example 4 was formulated as Part A, containing approximately 12ppm of platinum, and Part B containing 8.23lpp of polymeric silicon hydride, Gelest / ABCR HMS-151, in addition to siloxane inhibitor. The mixture was analyzed in the rheometer at a temperature of 35 ° C, as described above. The cutting module G ', after 3000 seconds for the proportions B / A were: 0.821, G' 100.7 kPa; proportion: 1.00: G '167.9 kPa; proportion: 1.22, G '193.2 kPa; proportion: 1.52, G '184.0 kPa.

Example 7 Implantation of silicone material in pig carcass eyes A fresh pig carcass eye was prepared, with a small opening incision inside the capsular bag and the crystalline lens was removed. The silicone composition was prepared from the prepolymer of Example 4, which has a refractive index of 1428, with a Part A containing ca. 12 ppm of platinum in the form of a complex of divimtetramethyldisiloxane, and a Part B containing tetracycderimethylsiloxysilane crosslinker, mix 18.9 mg / g, with siloxane inhibitor. The gel time was approximately 16 minutes at a temperature of 20 ° C. Silicone was prepared for injection, mixing equal weights of Parts A and B in a Teflon pan, loading them into a syringe, evacuating gases, and then injecting it into the capsular bag through a 21-gauge cannula, to fill the bag and produce the appropriate curvature. After healing (ca. 45 minutes from the start of mixing), the lens was removed from the oo. The free transparent tip lens had an anterior radius of 10.1 ± 0.4mm, a posterior radius of 5 ± 0. lmm, thickness of 5.33 ± 0.03mm, diameter of 9.2 ± 0.1mm. Its power in air was 11512 diopters, and focal length of 8.7 ± 0.1mm (in water, the power of the lens was 29,110.5 diopters, and focal length of 45.710.8mm). The natural crystalline lens of the pig, has a Rl superior to that of the human lens. From the measured dimensions of 11 pig lenses, it was calculated that an Rl of about 1.51 is required to restore the natural refractive power in a filled pig lens.

Example 8 Implantation of the silicone material in a cadaver eye of a human A cadaver eye of human was prepared, with a small opening incision in the capsular bag and the crystalline lens was removed. The silicone composition was prepared and a lens was made as in Example 7. The transparent free tip lens had an anterior radius of 8.7 ± 0.5mm, a posterior radius, 6.2 ± 0.1mm, a thickness of 4.11 ± 0.06mm, a diameter of 8.2 + 0. lmm It was calculated that the focus length of 49.08mm produced a power in water of 27,110.7 diopters. The power in water of the average human lens is 21.8 diopters, and to have obtained this power in the lens filled in the present invention, a filler material of Rl 1.41 would have been required.

Claims (22)

NOVELTY OF THE INVENTION Having described the present invention, it is considered as a novelty and, therefore, the content of the following is claimed as property:
1. CLAIMS 1. Polysiloxanes suitable for the preparation of intraocular lenses through a crosslinking reaction, having a specific gravity greater than about 1.0, a suitable refractive index to restore the refractive power of the natural crystalline lens and a viscosity suitable for injection through of a standard cannula.
2. 2. - The polysiloxanes according to claim 1, characterized in that the refractive index is within the range of between 1.382 to about 1.60.
3. 3. - The polysiloxanes according to claim 2, comprising at least one siloxane monomer with a specific gravity greater than about 1.0.
4. 4. - The polysiloxanes according to claim 3, comprising at least one siloxane monomer -RaRbSiO-, wherein Ra and Rb are the same or different alkyl or phenyl groups of which, at least one is substituted with one or several fluorine atoms.
5. 5. - The polysiloxanes according to claim 4, comprising fluoroalkyl (alkyl) siloxane monomers.
6. 6. The polysiloxanes according to claim 5, comprising trifluoropropymethyl siloxane monomers.
7. 1 . - The polysiloxanes according to any of claims 1 to 6, the terpolymer or polymer higher than three or more units of siloxane monomer.
8. 8. - The polysiloxanes according to any of claims 3 to 7, which comprises arylsiloxane monomers.
9. 9. The polysiloxanes according to claim 8, which comprise methyl and substituted methylsiloxanes, phenylsiloxanes and trifluoropropylsiloxanes.
10. 10. - The polysiloxanes according to claim 9, which are essentially a terpolymer of a) dimethylsiloxane, b) methylphenylsiloxane or diphenylsiloxane; c) and r-trifluoropropylmethylsiloxane monomers.
11. 11. - The polysiloxanes according to claim 6, comprising at least 4 mol of trifluoropropylmethylsiloxane.
12. 12. The polysiloxanes according to any of claims 2 to 11, which have a specific gravity within the range of from about 1.03 to 1.20, and a refractive index from about above 1.38.
13. 13. - An injectable lens material, comprising polysiloxanes having a specific gravity that is greater than about 1.0 and a refractive index comparable to that of a natural lens according to any of claims 1 to 12, a crosslinking agent having a adequate amount of non-reactivated Si-H groups and a catalyst.
14. 14. - A reaction mixture for preparing polysiloxanes of an injectable lens material comprising a plurality of siloxane monomers having a specific gravity in the range from 0.97 to 1.28, characterized in that the siloxane monomers comprise one or more trimers or tetramers or monomers of higher order cyclic siloxane forming a silicone lens material with a specific gravity greater than 1.0.
15. 15. - The reaction mixture according to claim 14, characterized in that the plurality of siloxane monomers is copolymerized to make a terpolymer with a refractive index of about 1.41 and a specific gravity of about 1.1.
16. 16. - The reaction mixture according to claim 15, characterized in that at least one of the monomers has a specific gravity that is greater than 1.0.
17. 17. The reaction mixture according to claim 15, characterized in that the plurality of siloxane monomers are selected from a group consisting of methyl and substituted methyl siloxanes, phenyl siloxanes and methyl trifluoropropyl siloxane.
18. 18. The reaction mixture according to claim 15, characterized in that the plurality of siloxane monomers consists essentially of cyclic dimethylsiloxane monomer, cyclic diphenylsiloxane monomer and 3,3,3-trifluoropropylmethyl cyclotrisiloxane.
19. 19. The reaction mixture according to claim 15, characterized in that the plurality of siloxane monomers consists essentially of cyclic dimethylsiloxane monomer, cyclosiloxane triphenyltrimethyl monomer and 3,3,3-trifluoropropylmethyl cyclotrisiloxane.
20. 20. - A method for preparing an intraocular lens, comprising: providing a reaction mixture according to any of claims 14 to 19; polymerizing the siloxane monomers to form a polysiloxane having a specific gravity greater than 1.0; transferring the polymerized siloxane monomers in a mixture together with a crosslinking agent and a catalyst for the capsular bag; and curing the mixture for the final lens
21. 21. - A method of preparing an intraocular lens that includes the provision of a mixture containing the polysiloxanes according to any of claims 1 to 12, a crosslinker and a catalyst by injecting said mixture into a mold and curing said mixture at the temperature of curing optionally under forming pressure for a sufficient time to prepare said lens.
22. 22. - A method according to claim 21, wherein the lens is injected into a capsular bag of a human eye and cured at an ambient temperature.