Fabrication of soft plastic contact lens blank

Holder ~ Same (71 (74) Agent:

(54) Contact lens and its manufacturing process.

72.

Invention of t ^ 33) (32) (31) Conventional priority: Patent application filed in the United States of America on Novenibre 1969, n. 880.828 to the names of Kenneth Fi O'DriscoH and Allan A. Isen.

Sale of booklets at IMPRIMERIE NATIONALE, 27, rue de la Convention - PARIS (15^e)

42863

The present invention relates to a method or process for forming and polymerization, at low temperature (40 to 602C) and at medium temperature (90 to 120^sC), of a dispersion of a polymer in a monomer, by pouring into a mold and continuing the polymerization after removal from the mold, the dispersion preferably consisting of 20 to 45% of polymerized vinylpyrrolidone and from 80 to 55% manomethacrylic esters of a glycol chosen from the group consisting of ethylene glycol, propylene glycol, diet hylene glycol and dipropylene glycol, free methacrylic acid not exceeding 1% by weight and the dimethacrylate of the said esters not exceeding 0.2% by weight. Amounts of excess impurities outside these limits cause obscuring or clouding, unacceptable hardness of the molding after hydration, and a decrease in the amount of water absorbed by the hygroscopic polymerized solid. The monomer is mainly a pure hydroxyalkyl methacrylic ester.

An essential characteristic of the process according to the present invention is the post-polymerization step of the molded and solid polymerized mass after induction of free radicals "at low (40 to 60^sC) and medium temperature (90 to 120 ^ 0) by means of (a) a polymerizing irradiation of the dry solid, and (b) a treatment with hydrogen peroxide of the product swollen with water in a saline solution isotonic which brings the solid post-polymerized product to a state of complete hydration (the swelling water participating for 45 to 80%) which is proportional to the content of polyvinylpyrrolidone.

As prior art we can cite:

- U.5 patent. 2,136,422 (FIELDS), which describes the mass polymerization of ethylene glycol monomethacrylate with a free radical initiator such as benzoyl peroxide at elevated temperatures to produce a perfectly transparent solid which is cut and passed through to produce table legs or the like.

- U.5 patent. 3,086,956, (ARMEN and others) which, in its example 7, describes the polymerization of glycol monomethacrylate with polyvinylpyrrolidone and ammonium persulfate as initiator, at pH 5 in the presence of water, in order to provide a copolymer graft

42863 as a Suspension in water containing 19.7% dry matter.

- US Patent 2,923,692, (AC.KERMAN and others) which describes weakly crosslinked copolymers of esters of methacrylic acid and vinylpyrrolidone (see column 7 line 32). The products thus obtained contain cross-linked acrylic acid groups, highly sensitive to water, which can be neutralized by alkalis to form a smooth and continuous mucilage after the product has been purified by washing, dried and passed through a homogenizer or a colloid mill.

-We could expect that the mass polymerized ester of FIE-L05, neutralized, hydrated, washed and ground by the ACKERMAN method would lead to mucilage or a glue * We have found that before grinding, the product had a limited hydration capacity (at most 20 to 30 even with substantial quantities of acrylic or methacrylic acid in the interpolymer or the copolymer. Reference will be made later to the hydrophilic lenses described in patent U .5. 3.048.429.

, - U.5 patent. 2,941,980 (R0BIN5QN), which describes polymers and water-soluble copolymers of pyrralidone with several kinds of monomers such as acrylic acid, vinyl acetate, and others; these water-soluble polymers are mixed with alkylated phenols serving as plasticizers to provide base coatings for metals, paper, glass, etc. to ensure their protection against water.

The accelerating effect of at most 1% vinylpyrroli— done on the polymerization of methacrylic esters is. known from patent U.5. 3,232,912, (MUNDAY) but the polymerized products are liquids or solids with low melting point, used as detergents in lubricating oils and as mud dispersers in heating oils.

The copolymers of vinylpyrrolidone and of acrylic acid, according to RDBIN5ON, or of grafted polymers of glycol methacrylate with vinylpyrrolidone, according to ARMEN, - are not satisfactory for producing contact lenses swollen with water. These products form low resistance films which, when impregnated with water, are easily distorted by forces of

42863 tension and have a low power of recovery, improper elongation and hardness.

It should not be expected that the polymers grafted in the proportions recommended by the above-mentioned authors can be used to form hard, transparent, and hydro-swollen contact lenses capable of being cleaned and sterilized with hydrogen peroxide.

In general, the process according to. the invention consists in transforming a solid polymer, induced in free radicals, containing polyvinylpyrrolidone and a polyhydroxyalkyl methacrylate, into a formed mass, hydrated, soft to the touch and highly permeable, having a hardness, an elasticity and a power increased recovery by treating the dry solid mass by irradiation to assist densification, and subsequently by hydration of the mass in a saline solution and its treatment with hydrogen peroxide which produce additional copolymerization between the polyvinylpyrrolidone and the polymerized methacrylate.

In a preferred embodiment, a resistant, soft, hydrated and fluid-permeable contact lens cut from a blank is prepared by molding a composition consisting essentially of 20 to 45% of solid molecular weight polyvinylpyrrolidone high in order to obtain a network of 80 to 55% of ethylene glycol methacrylate, or of propylene glycol or of diethylene glycol, which must not contain more than 1% methacrylic acid as impurities and, if possible, less than 0.2% and not more than 0.2% ethylene glycol dimethacrylate. The polymerization of the raw and preformed polymer mass is carried out in stages, the first taking place in a mold and the following hdrs of the mold, as follows j (1) - in the open mold, with a peroxide at low temperature such that acetyl peroxide, dicarbonated secondary butyl peroxide, cyclohexanone peroxide, etc., at 40-60 ° C for a period of 4 to 24 hours.

(2) - outside the mold, at medium temperature, with a free radical initiator, such as benzoyl peroxide, diethÿle peroxide, azoisobutyronitrile, orthotolyl peroxide, etc.

42863 at a temperature of 90 to Il20^sC for a period of 30 minutes to 2 hours; .

(3) out of the mold, in polymerized mass, formed, hardened using actinic or high energy radiation, such as ultra-violet, gamma radiation, etc. after the lens has been cut to size; and _ (4) - finally in the hydrated state with hydrogen peroxide and in the presence of salt which produces the osmotic equivalent of a normal saline solution, whereby the lens cut and swollen with water, containing approximately 40 to 80 of water, but preferably 50 to 60 is cured in the wet state to a remarkably high degree compared to that imparted by normal hydration of the lens in the absence of steps (3) and (4).

Step (3) increases the hardness of the lens in the hydrated state by about 100 Ί as it emerges from a burst measurement, in a bubble, and step (4) further increases the hardness at least 200% hydrogonflated lens and allows the lens to be cleaned of pollution from the eye by subsequent treatment with hydrogen peroxide. .

It was completely unexpected to be able to obtain a graft of glycol methacrylate practically free of methacrylic acid from polyvinylpyrrolidone and making it possible to obtain by casting of these materials blanks which. are hard, dimensionally stable and uniformly reproducible in a hydrated form and swollen by 40 to 80% of water, and in which the permeability of the hydrated product has been increased by a post-polymerization treatment, firstly, by means of irradiation in the dry state, and in. second, using hydrogen peroxide in isotonic saline. .

The function of polyvinylpyrrolidone, with a K de.Fikentscher index of 30 to 90 in the preferred embodiment of the invention, with regard to the treatment with hydrogen peroxide, appears to be essential in the new and unexpected properties, hardness elastic recovery and elasticity, obtained by graft copolymerization with a hydroxyalkyl acrylate.

Polyvinylpyrrolidone is comparable to gelatin and albumin in view of its strong affinity for water, its original faibad

42863 ble toxicity and its bio-chemical inertness in general. The polyvinylpyrrolidone which is preferred for making contact lenses in accordance with the invention, has a Fikentscher K index of 33, corresponding to a molecular weight of approximately 25,000 to 50,000, the average molecular weight measured by osmometric route being 37,000. about, which is about half the molecular weight of albumin in beef blood.

The carbonamide groups present in gelatin are responsible for the fibrous structures in hydrated gelatin emulsions which have been detected under the microscope in grain-free photographic emulsions obtained from solutions of 5 to 10% of gelatin adjusted to the isoelectric point. .

Surprisingly, the photographs of the lens structures treated with hydrogen peroxide according to the present invention and taken with an electron microscope (of the scanning type) do not show fibrous structures but instead show collapsed spheres which are distributed at through the non-crystalline matrix. These spheres communicate hydroscopic characteristics to the product which contribute during the post-polymerization with hydrogen peroxide to create a microscopic alteration so significant which makes it possible to increase the permeability and the diffusibility, through the membrane of the polymer, of dissolved products. in water. This polymer membrane treated with hydrogen peroxide, used as a contact lens, can be cleaned with hydrogen peroxide to remove the catalase deposited under the action of tears and other organic debris which tend to accumulate in the Wichterle hydrophilic contact lenses.

Hydrogen peroxide has the effect of ridding the interstices of the lens of catalase and other muco-proteins of the eye. At the same time, it somewhat increases cohesion without affecting the permeability to fluids which is such an important factor in proper functioning. This latter effect is much greater than the initial hardening of the product, which is achieved by the first washing with hydrogen peroxide. The use of hydrogen peroxide, therefore, becomes a maintenance technique which not only sterilizes the lens, but is one of the key factors in maintaining clarity, transparency and permeability

42863 to fluids.

This treatment thus avoids eye irritation and prevents the development of edema under the lens when the lens is worn continuously for 24 hours or more.

The product of the present invention, treated with hydrogen peroxide, appears to have properties significantly different from gelatin in its resistance and inertness to acids, alkalis and at relatively high temperatures in the wet state. Since gelatin is amphoteric, it reacts with acids and bases and dissolves reversibly under the effect of heat until denaturation and flocculation above a certain temperature in an aqueous medium. On the contrary, the product of the invention supports boiling water for more than 72 hours without altering its interesting characteristics of permeability. Although the chemical mechanism of the alteration of carbonamide bonds by irradiation, and polymerization with hydrogen peroxide could not be fully explained, it is clear that a significant and significant strengthening of the physical properties has been obtained and it cannot be obtained by any other method.

In the manufacture of contact lenses made of a non-irritating plastic material and swellable with water, from a raw and dry part, or blank, according to the preferred method of the invention, a simple casting device is used for form the part and polymerize it, as shown in the appended figures in which:

Fig. 1 is an elaboration diagram showing the mixing of the ingredients, their stirring, their degassing, their introduction into the mold and the placing of the mold in an oven for the first and the second stage of cooking at low and medium temperature respectively, to lead to a hard, transparent, formed mass which is subsequently subjected to cutting and polishing.

Fig. 2 is a schematic view showing the arrangement of the male and female parts of the mold to form the hard and transparent solid which will be subsequently cut.

Fig. 3 is an elaboration diagram showing the manufacturing steps in a particularly preferred form

42863 î 2077538 according to which the irradiation treatment, the swelling in an alkaline medium, the osmotic swelling and the hardening with hydrogen peroxide are carried out in order to improve the physical properties and the water permeability, and to reduce the swelling osmoti5 only of the cut and polished lens.

Figs. 4_at, 4^, 4_VS and 4, -j show the steps from the size of the mass formed out of the mold of FIG. 2 until the lens is finished, and ·

Fig. 5 is a sectional view showing the interpretation of the mold and of the hard transparent mass formed after the first stage of cooking and before removal from the mold.

The invention will be better understood on reading the five examples of application of the method of the invention which will now be described in detail in relation to the said figures.

Example 1: To 120 parts of distilled hydroxyethylmethacrylate containing less than 0.2% dimethacrylate and less than 1% free methacrylic acid as impurities, 40 parts polyvinylpyrrolidone powder (Plasdone Grade C, supplied by GAF Corporation) are added having a Fikentscher K index of 33, an average molecular weight of 37,000, a molecular weight range of 25,000 to 50.0D0 with an olafond at 15% of the distribution of the K index including 39% by weight of polymer and a floor at 25% including 18.5%. This polymer hereinafter designated by

PVP is hygroscopic and has a humidity of around 3 which can still rise by 1 to 2% in a humid atmosphere.

A quantity of 40 parts of liquid methacrylate, hereinafter called HEMA is mixed with a catalyst, for example 0.2 grams of benzoyl peroxide powder and 0.2 grams of secondary butyl peroxide dicarbonate, (available under the name commercial of Lupersol 225 to the Lucidol Chemical Corporation, Buffalo, New York).

The liquid catalyst mixture in an amount of 40 parts, is added to 120 parts of the PVP - HEMA mixture, and is mixed thoroughly to form 160 parts of monomer with 40 parts of a paste-based dispersion of polymer. These proportions lower the contraction, compared to HEMA alone. PVP is present

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42863 β 2077538 in a proportion of 20% by weight in the dispersion. The dispersion is degassed to allow air bubbles to escape and the mold is filled, as shown in the diagram in FIG. 1. The molds are then placed in an air circulating oven for a period of 20 hours, at 4Q^eC. At the end of this period the molds are removed from the oven and removed from the mold using a rod to press against the end. flat Teflon sleeve at the bottom of the mold. This forces the molded part to come out at the other end of the sleeve. The molded blanks are placed on aluminum foil and returned to a container. oven where they are post-baked at 110^eC for an hour and a half. When removed from the oven again, the blanks are a polymer made of PVP to which poly-HEMA has been grafted.

Example 2: the molding process is derived from exeia15 pie 1, but instead of $ 20 by weight of PVP we use $ 30>. The lenses obtained by the process of Example 1 contain approximately 55% of water, measured in isotonic saline solution, and finally constitute lenses having the same standards as in Example 1.

Example 3: The process of Example 1 is repeated except that diethylene glycol monomethacrylate is used with 25% by weight of PVP. The resulting lenses still have the same standards as in Example 1.

Example 4: The process of Example 1 is repeated except that, instead of 20 of PVP, 35% by weight is used, without changing the standards.

Example 5: a mixture of 80 parts of propylene glycol monomethacrylate and 80 parts of HEMA is used as the monomer phase with 20% by weight of PVP and the operating process is that of Example 1. The lenses obtained reach the high standards of example 1.

The water content of the lenses obtained according to Example 1 is approximately 51% with swelling in pure water, and approximately 49.5% in 0.9% saline solution. On the contrary, the hydration of poly-HEMA without PVP is approximately 38 to 36%. The hydration of the lenses of the other examples is substantially the same as that of Example 1 "In general, the main

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42863 differences obtained by substituting HEMA for prolylene glycol or diethylene glycol monomethacrylate are the lowering of the refractive index and the bending ability of the polymerized solid.

If in the previous examples PVP is used in amounts of less than 20%, the hydration value of approximately 40 - 50% is not reached in the basket of polymer swollen with water, and the desired hardness and the increase in resistance is not achieved by the subsequent treatment with hydrogen peroxide.

If the initiator is omitted at low temperature and polymerized at 90 - 120^sC for 30 minutes to 2 hours, the solid product is not uniform in its physical properties.

Without the two initiators at low and medium temperature, the improvement in permeability compared to the commercial product Soflens produced according to the WICHTERLE patents, is not achieved any more than a constant reproducibility.

Thus the two primordial stages of initiation at a temperature of 40 - 6Q²C in the mold to form the solid rod and at 90 - 120^atC outside the mold, on a baking sheet, to harden the already consistent rod, provide a rod of storable material with a hardness index (Shore A) between 70 and 90 which can be cut and polished into lenses by the usual techniques implemented with dura acrylic materials. Even without further treatment, such lenses can be hydrated and swollen with water and then exceed the performance of hydrophilic lenses which are currently commercially available.

If more than 45% PVP is used in the polymerized mass, the mass, after hydration, becomes excessively soft.

Even after post-polyroérisaticn, the product can not be hardened to compete with the high values ​​of firmness and elasticity, preferred examples above.

Only in the range of 20 to 45% PVP does the present polymerized composition, free of crosslinking, riva35 read with the mechanical properties of 5oflens ^B commercial.

Soflens material does not have the same permeability which, in the examples cited, is 10 to 15 times stronger than that

42863 Soflens equipment.

MANUFACTURE OF LENSES

The manufacture of contact lenses in the hard state and the subsequent process after hydration and finishing in the soft state are described and claimed in a patent application by ALLAN A. I5EN one of the inventors of the present invention, and relating a method for pruning soft contact lenses treated with hydrogen peroxide and a new lens resulting therefrom.

The lenses are obtained by cutting and polishing the mass formed, in the hard state, as shown in the working diagrams of FIG. 1 and in Figs. 2, 4_at at 4 ^ and 5, and it appears that the process is the same as for an acrylic lens.

The molding ingredients, comprising the mixture of hydroxyalkyl methacrylate, of PVP, of initiators at low and medium temperature, undergo the first stage of cooking in mold and the second stage of cooking on plate, to lead to flat cylinders. concaves such as 20, hard, transparent, as shown in FIG. 2. The concave surface is formed by a male member 10 of the mold, fitted in a female member 11 · The inner surface of this female member 11 is coated with Teflon, as is the outer surface of the male member 10. After cooking, the The hardness index of the mass formed is between B0 and 90. The following post-polymerization treatment increases the hardness by 3 to 10 points. For a higher PVP concentration, lower initial hardness indices are obtained.

The subsequent treatment, for example post-polymerization by irradiation, leads to a greater increase in the hardness index at high concentrations of PVP and this demonstrates that the irradiation is particularly effective in the post-polymerization of the PVP part of the product. . The irradiation also tends to cause a slight brittleness, and it is preferable to cut the mass 20 before the irradiation treatment "

Due to the PVP content in the lenses and the two stages of cooking, there remains no trace of uncured material in the mass formed or blank, and the lenses

42863 cut which are prepared according to the steps shown in Figs. 4θ to 4 ^ have water swelling characteristics going well beyond those of hydrophilic lenses of the prior art, commercially available. The commercial product Saflens produced by the BAUSCH Company and LOMB has a water content of 38 ί to compare with the content of 30 to 50% of the cut lenses of FIG. 4 before irradiation and treatment with hydrogen peroxide. This combination of high hardness in the dry state and a high water content in the hydrated state allows a simpler and completely different manufacturing process than that which must be carried out with WICHTERLE lenses which must be cut after being mounted on a support, as described in patent U.5. 3,361,858. The material according to the present invention does not contain any crosslinking, which constitutes the lenses according to the said patent, and it is surprising that the practically pure matrix of poly-HEMA of the invention, having a hardness close to 90, can be easily with cut in the dry state very low tolerances of the order of 1/100 mm, and then can be hydrated to 50% more than the lenses of the prior art. This size in the dry state makes it possible to obtain extremely fine edge sections and allows a uniformity in the manufacture which cannot be obtained with the methods of manufacture of the prior art.

In the dry state, the refractive index of the blank 20 is approximately 1.49. In the hydrated state, the refractive index is approximately 1.39 to 1.40. The lenses become larger, thicker and flatter after softening by hydration. During the process of pruning and polishing the lenses, a relaxation takes place in the shape, and they become a little more domed and slightly larger in diameter. All these modifications are taken into account to obtain, after hydration, the required dimensions and curvature standards.

The lens blank 20 is a small cylinder which has a concave curvature at one of its ends which must be optically worked, and a small amount of material is removed from this surface, for example a minimum thickness of

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42863

0.2 mm and maximum of 0.5 mm, the withdrawal being carried out symmetrically over the entire surface.

The following relate to the manufacturing steps after the blanks 20 are baked at low and medium temperatures. After cooking at low temperature, the blank 20 is removed as shown in FIG. 5 where a rod 13 is pressed against the flat surface of the blank to eject the blank out of the female part 10 of the mold. The blank is removed by the same end through which the dispersion or paste was introduced, and this removal is completely different from that which is practiced according to US Patent 3,361.B5B, in which the lens is molded to dimensions on a mounting and is removed from the assembly by immersion in water to inflate it and allow it to be detached from the assembly. After that, the blank of the present invention is baked at medium temperature on a plate and the steps are continued as follows.

Step 1: size

The size steps are shown schematically in Figs. 4_g at 4 ^. The dotted lines in FIG. 4_g show the removal of peripheral or radial partitions from the blank in order to reduce the angular opening from 18QS to approximately 1202, as shown in FIG. 4_g and Fig. 4 ^.

The flat surface is then cut, according to the dotted line located at the bottom of Fig. 4 ^ in order to facilitate the mounting of the blank on a lathe, and this blank is shown in 4_VS. In the case where the jaws of the lathe can grasp the shape of FIG. 4 ^, the plane size shown in 4_VS is not necessary. The concave cut is made along a dotted line shown in FIG. 4_vsand the cut lens is seen in 4 ^.

In a lens obtained according to the present invention, the flat surface of the back of the blank is surfaced, as indicated in Figs. 4d, and 4_VS, and the center of the flat surface is tarau dice to serve as a holding pivot on a small jeweler's turn The diameter of the blank is reduced in the Levin turn to a dimension exceeding by 0.1 mm the dimension of the finished lens ( see Fig. 4θ) „The radius of the waist on the concave surface corresponds to the radius of this surface.

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Step 2: polishing the inside or back

The concave base blank is then mounted on an optically polishing machine and it is polished against a brass polissary coated with an adhesive felt, the curvature of which corresponds to the curvature of the base of the lens. During polishing, the preform swings back and forth on the polisher, and rotates at the same time. Two polishing cycles are used. The first uses the compound Snow Floss, produced by Johns MANVILLE, mixed with deodorized Kerosene, until the consistency of a thick paste. This rough polishing is continued for 3 minutes. The final polishing is done with Zinc oxide (grade U.5.P.) produced by MERCK, mixed with petroleum jelly to form a paste. This frosting cycle is also continued for 3 minutes. When the curvature is finished, it is examined with a curviscope, and it must have a radius of curvature of the waist at + 0.04 ram.

Step 3: size of the radius of the exterior or front surface

The base thus completed is then mounted on a brass or plastic mandrel for cutting and polishing the front surface. This mandrel has a finished, polished, convex surface which corresponds to the base of the finished blank. The chuck split is adapted to the collar of a high-precision jeweler's lathe as produced by LEVIN and SONS. The mandrel is heated slightly and enough to melt a small amount of wax on the surface of the mandrel. The finished base is applied firmly to this surface and allowed to cool. The mandrel is then mounted on a Levin lathe and the front surface is cut radially in two stages. During the first, coarse pruning removes excess material. During the seconding a finishing size gives a very soft spherical surface and an exact thickness in the center. The thickness is measured by a thickness gauge through a small diameter hole drilled in the center of the mandrel, which is also used to assess the optical qualities when finishing the lens. The front surface then receives an optical polish. The mandrel, mounted on a vertical spindle, is rotated like a polisher, covered with adhesive felt, swings back and forth on the surface and rotates at the same time

42863 time. The polishing paste used is the compound 5now Floss mixed with deodorized petroleum, until pasty. It takes three minutes to perfect the surface, and the optical quality is assessed by removing the mandrel from the spindle and inspecting the optical surfaces with a lensmeter through the hole in the mandrel.

Step 4: size of lenticular edges on divergent lenses

In the case of divergent lenses it is necessary to thin the edges by an additional divergent size on the front periphery of the lens. This is done with a single-edged razor blade and the subsequent polishing is carried out using foam and the zinc oxide polishing solution. The width of this lenticular front must not be greater than the half the diameter of the lens.

Step 5: adding an interior bevel and inspection

The lens is then removed from the mandrel by heating the bottom of the latter until the wax remolves and; the lens can slide easily from the mandrel; it is then cleaned in a test tube with xyle, in an ultrasonic cleaner.

The finishing of the lens includes the addition of a small flat bevel on the inside of the edge, d¹ approximately 0.3 mm wide. This is done by lapping against a sphere of emery or against a felt impregnated with diamond paste and by polishing with felt. Following this, the edge is rounded and polished on a polyurethane sponge saturated with polishing mixture or zinc oxide and deodorized petroleum. The lens is then cleaned again with an ultrasonic cleaner. It is then checked and inspected with regard to the radius of curvature of the base, the optical qualities, the thickness and the surface condition.

Step 6: irradiation treatment as shown in Fig. 3

The irradiation is preferably carried out under an ultraviolet ray lamp, which produces high energy radiation in the band from 2000 to 4000 Angtroms, for at least 1/2 hour, and preferably for 2 to 4 hours. The bursting resistance goes from 490 g / cmZ to 735 - 770 g / cmZ, which consti70 42863 is 2077538 kills an increase of at least about 5D, of the original value without the hydrated lens losing practically none of its qualities of elasticity and speed of recovery. On the contrary, the Solfens commercial product of prior art lenses is not improved by irradiation with regard to its resistance to bursting. Therefore, it is clear that the PVP of the new composition, as well as the two-step polymerization process, such as low temperature initiation and medium temperature initiation to which the

Fig. 1, cooperate in a new way with the irradiation treatment of the solid in the polymerized state to produce this new and unexpected result ”

Ultraviolet sources such as a mercury vapor tube, a xenon lamp or a carbon arc tube can be used.

Other sources of irradiation that can be used include a Cobalt 60 source that emits gamma radiation, used reactor elements from a uranium cell that also emit gamma radiation, or high ionizing energy produced from commercially available sources, X-rays from a Radiation Dynamics device, Long Island, New York with an exhibition of 10? Roentgens for a period of 15 minutes to an hour. Exposure to gamma radiation for the post-polymerization treatment is preferably about 5 to 95 Mega-rads for a period of 5 minutes to an hour. All irradiation treatments are carried out at room temperature.

In this irradiation treatment, as shown in FIG. 3, the hard lens, finished, is placed in pure ultraviolet light, for a period of three and a half hours. The light source is 15 cm from the lens. The ensemole is covered to prevent light loss, and the polymerization of poly-HEMA and PVP is complete after two hours. The light source is a Spectraline ultra-violet lamp of

250 Watts.

Step 7: Neutralization, hydration and treatment with hydrogen peroxide

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42863 is 2077538. During this step, neutralization and 1¹ lens hydration. The lenses are placed in a 0.8% saline solution containing the sufficient quantity of baking soda to bring it to a pH of 8. They are left in the bath for 2 to 20 hours. Each lens is supported in a small openwork palypropylene basket. Then the lenses are placed in a bath of normal saline at about 932C for one hour. The bath is then replaced by a fresh saline solution for a duration of 3 hours, then again changed for a duration of 4 hours. This scalding is carried out in an autoclave equipped with a condenser to avoid evaporation and the increase in the salt concentration.

Then the lenses are placed for 4 hours in a hydrogen peroxide bath at 10 volume (3% HgOgî to which has been added the amount of pure sodium chloride sufficient to produce the equivalent of a normal saline solution. causes the lenses to contract and go into hypertonic state. Following this, they are boiled in an autoclave, in distilled water, for a period of two hours, and again in normal saline for 2 hours (see Fig. 3).

RE5I5TANCE IN LENS BREAKING:

The steps (6) and (7) of post-polymerization, irradiation and treatment with hydrogen peroxide, illustrated in FIG. 3, contribute significantly to the strengthening and hardening of the water-swollen lenses and thereby provide advantages not found in any of the commercial lenses of the soft hydrophilic type. . .

The hard cut lens resulting from the manufacturing operations of Figs. 1 and 4 ^ to 4 ^ can be examined with regard to the bursting resistance surrounding the edges of a lens of the nozzle of a 6 mm pipe and by measuring the air pressure necessary for bursting of the lens which was boiled in water for four hours to hydrate it. This test, performed on a lens of the invention, showed a burst strength of 790 g / cm 2. This lens, based on a poly-HEMA matrix containing .20% PVP, has reached the resistance to original ORIGINAL

42863 (490 g / cm²) of a Soflens molded by centrifugation containing a dimethacrylate reticulum, thereby showing an unexpected improvement in the absence of reticulum and a water content almost of 50% higher (52% in the lenses according to the invention against 37% in the Soflens).

After irradiation and treatment with hydrogen peroxide by the methods of the invention, the burst strength measured by the test indicated above is increased by 735 - 770 g / cm² up to 1120 - 1190 g / cm², which constitutes an increase of at least 250% compared to the original resistance and an increase of approximately 100% of the original value compared with the increase of 50% achieved by irradiation.

This enhancement of the resistance by hydrogen peroxide is solely based on the PVP content since the commercial soflens do not exhibit such an enhancement of the resistance. In the unique case of the invention, the treatments both by irradiation and by hydrogen peroxide are essential if we want to reach the maximum, of resistance and if the other properties of the lenses, for example a controlled elongation in the lateral and vertical dimensions when inflated with water, must be maintained.

These other properties of the lenses, in the inflated state, will be more clearly illustrated by comparison with the shape and dimensions of the hard lens of FIG. 4 ^.

By immersing the lens in water at pH 0 after irradiation (see the third rectangle in Fig. 3) the radius of curvature of the lens increases by 26%, the diameter by 35% and the thickness by 23%. These anisotropic expansion values ​​do not change if the lens is immersed in saline (fourth rectangle in Fig. 3). Water absorption is between 48 and 55

The hydrogen peroxide treatment provides the most surprising improvements in the physical properties of the hydrated lens, improvements which facilitate the maintenance and cleaning of the lens by the patient. By this treatment is obtained, · as mentioned above, an increase in burst strength after irradiation from 735 - 770 g / cm ^ to 1120 70 42 863

1190 g / cm ^ a If the 1% alkaline sodium bicarbonate solution at pH 8: is applied to the lens repeatedly, a slight softening occurs and the burst strength drops to approximately 875 - 945 g / cm ^. This effect is reversed by immersion in a 3% solution of hydrogen peroxide to regain the value of 1120 - 1190 g / cm ^. Repeated treatment with hydrogen peroxide, interspersed with softening treatments with alkaline bicarbonate solution increases the burst strength up to values ​​of 1330 - 1400 g / cm ^.

FLUID PERMEABILITY CHARACTERISTICS:

The fluid permeability of the lenses of Example 1 is studied and compared with the Soflens ”from BAU5CH and LOMB manufactured according to the method of US Pat. No. 3,408,429.

Individual vials of sterile fluerescein solution are prepared at different concentrations of disodium fluorescein in decinormal phosphate buffered solution at pH 7.4.

The concentration of fluorescein is measured with a slit lamp objective fluorophotometer, on the pupil and in solution. The fluorophotometer consists of a light-sensitive device incorporated in the lamp pupil and measures the concentration of fluorescein over an area of ​​80 microns.

The accuracy of the instrument is + 2% ”The value sought is compared to a fresh, stable and standardized fluorescein solution.

RESULTS OF5 STUDY5 IN VITRO IN COMPLETE HYDRATE CONDITION î - Absorption:

The fully hydrated lenses are placed in fluorescein solutions of different concentrations; they are rinsed quickly after the test time in solutionsaline and they are mounted at the end of a glass test tube for the measurement of the fluorescein concentration of the lens.

The lenses themselves absorb less than 3% of the light emitted and do not interfere with the result of the experiment by light absorption. The volume of the impregnation solutions is large compared to the volume of the lens.

The lenses are put under uniform fluorescence under.

42863 the lamp slit after 90 seconds of soaking in a solution of fluorescein at 5 x 10 “^ mg / ml. Three distinct zones are observed in Soflens lenses soaked for 30 minutes, due to the slow diffusion of fluorescein inside the lens. The lenses of the present invention absorb fluorescein much faster; absorption is complete after two hours. The BAU5CH and LOMB (.Soflens) lenses absorb fluorescein slowly and continuously throughout a 24 hour period, reaching a final concentration of 2.3 times that of the lenses of the present invention.

- Elution studies:

After pre-soaking the lenses for 24 hours in a solution of 5 × 10 -3 mg / ml of fluorescein, they are placed in 4 ml of buffered saline and the rate of change of concentration in the lenses and the eluting solutions is measured. After one hour, the lenses of the present invention released 70% of their fluorescein into the solution, while the Soflens released only 25%. It was only after B hours that the Soflens ”released 90% of their rescein fluo20.

After the elution of each of the lens types, it was determined that the Soflens absorb twice as much fluorescein as do the lenses of the present invention, equal to the weight of the lenses.

The total fluorescein content is linearly related to the concentration of the soaking solutions over a concentration range from 5 × 10 -6 mg / ml to 20 mg / ml, or one. range from 1 to 4000. The lenses according to the invention are air dried, placed in the fluorescein solution and the absorption of dry lenses has been found to be substantially identical to that of fully hydrated lenses.

RESULTS OF IN VIVO STUDIES s.

The study is carried out on a young woman who had already worn both conventional lenses and hydrophilic lenses without particular difficulty. The first day he was made to wear on one eye a lens of the present invention and no lens on the other eye. A single drop of ORIGINAL fluoresBAD

42863 2% sterile cetin was instilled into each eye at O, 2, 4, and 11 o'clock. The concentrations in the cornea and in the anterior chamber were measured after 2, 4, 6 and 24 hours, each time removing the lens ten minutes before the measurement.

A week later on. subject wore a BAUSCH and LOMB Soflens lens on one eye and a hard classic methylene glycol methacrylate lens on the other eye.

Drops were instilled at 0, 2 and 4 hours and measurements were made at 0, 2, 4 and 6 hours; after this time the BAUSCH and LOMB lens was removed. The fluorescein concentrations of the cornea and of the anterior chamber are reported in Tables 1 and. 2,. · Further. The concentrations of the cornea, and of the anterior chamber were higher with the lenses of the present invention, than with the other lenses. No difference was noted between the trial without lens, with standard methacrylate lens or with BAUSCH and LOMB lens. After 6 hours the fluorescein concentrations of the cornea and of the anterior chamber of the eye wearing a lens according to the invention were 6 to 8 times those at20 dyed with any of the other modes of treatment. In addition, the lens of the invention has been able to maintain the fluorescein concentration in the eye tissue for 24 hours despite the well known rapid evacuation of fluorescein from the eye. lens was not pre-soaked in la-fluorescein before insertion.

In other studies, the lenses of the invention were pre-soaked in solutions of $ 0.1 and 0.01% fluorscexene and inserted into the right eyes of milk rabbits, together with a drop of the 0.01% solution in the left eyes; 90 minutes later, the lenses were removed, the eyes were irrigated with saline and the concentrations in the cornea and in the anterior chamber were measured. The lenses were then reinserted and the rabbits received a drop of the 0.01 $ solution in the left eye, every thirty minutes, for an additional two hours. Saline was instilled into the right eye. Fluorescein concentrations in the cornea and aqueous humor at 1.5 hours and

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42863 three and a half hours are given in Tables 3 and 4 below. The ocular concentrations reached with pre-soaked lenses were four times higher than those reached with frequent instillations.

The 10-fold increase in concentration of solution d¹ imbibition gave an 800% increase in concentrations in the eye; it would have taken much less fluorescein to reach the same ocular concentration if the fluorescein had been soaked in the lens, instilled locally ·

TABLE 1

Corneal fluorescein concentration for different types of contact lenses.

(Values ​​must be multiplied by 10 “^ mg / ml)

Time (hours) lens of the invention BAOSCH and LOMB lens

Methyl methacrylate

NOT^s of lens

<td> 2</td><td> 14</td><td> 6</td>

<td> 4</td><td> 81</td><td> 17</td>

<td> 6</td><td>15D</td><td> 25</td>

<td> 24</td><td> 220</td><td></td>

4,5 9 · 13

24

TABLE 2

Fluorescein concentration in the anterior chamber for different types of contact lenses (Values ​​must be multiplied by 10 “^ mg / ml) Time lens (hours) 1¹ invention

17

115

235

184

<td>lens</td><td>Methacrylate</td><td>NOT^e from len ·</td>

<td>BAUSCH and LOMB</td><td>of methyl</td><td>tille</td>

<td> 6</td><td> 4</td><td> 13</td>

<td> 19</td><td> 19</td><td> 26</td>

<td> 27</td><td> 21</td><td> 28</td>

<td></td><td></td><td> 14</td>

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T AB LEAU 3

Concentration of fluorescein in the rabbit cornea with prepreg lenses of the invention.

(values ​​must be multiplied by 10 ”^ mg / ml) (number of animals in brackets)

T emps (hours)

1.5

3.5 pre-impregnated lenses with 0.1% fluorescein

616 (3) lenses pre-impregnated with 0.01% fluorescein

107 (3) (3) instillation of 0.01% fluorescein (6) (6)

TABLE 4

Concentration of fluorescein in the aqueous humor of rabbits with prepreg lenses of the invention (the values ​​must be multiplied by 10 "^ mg / ml). (Number of animals in brackets) prepreg lenses prepregs with prepregs with fluorescein fluorescein

Time (hours) _ at 0.1% __ at $ 0.01

1.5 - 42 (3)

3.5 490 (3) 59 (3) 0.01% fluorescein instillation (6) (6)

OXYGEN PERMEABILITY STUDIES

The lenses of the present invention appear to have a higher oxygen transmitting power than commercial hydrophilic lenses, and therefore, are of good health with regard to the passage of oxygen through the lens to the cornea.

The lenses of the present invention, prepared according to the two-stage initiation process shown in. Fig. 1, without the two subsequent stages of irradiation and treatment

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42863 hydrogen peroxide, have characteristics of permeability and diffusion comparable to those, which have been reported above} and these lenses, cut from a polymerized rod, as shown in Figs. 4_at at 4 ^, are sensitive to cleaning and hardening with hydrogen peroxide, although to a significantly lower degree / 4-SS than lenses prepared according to the preferred method of the invention, as shown in FIG. 3.

The diffusibility of the solutes through the lenses prepared according to the methods of Figs. 1 and 3, is about 6 times to about 20 times greater than the diffuse of commercial Soflens products, this diffusibility being expressed by the speed of elution of an indicator through the lens. By way of comparison of the diffusion value it can be seen that a dye diffuses completely in a few hours through a lens of the invention, while such diffusion requires 24 hours or more for commercial lenses.

The significance of such a diffusion appears when a circular lens conforming to the patent application of the same applicants mentioned above, is placed in contact with the horn born on the hyper-sensitive peripheral area, its thin north extending from a few millimeters above said area, the peripheral crown of the lens forming a lacrimal vesicle cut from the material of the lens adjacent to the crown.

The vesicle of this new lens has the consequence that the solution of the lacrimal fluid remains clear in contact with the cornea and that an osmotic pressure is created in the direction of the lacrimal fluid which is less dense, towards the fluid of the cornea which is more dense, which contributes to the humidification of the eye. The semi-rigid edge is held against the sclera by attratian capil30 laire. Tears can enter under the rim to fill the vesicle which is immediately adjacent to the inner edge of the lens. Hypertonic drops instilled into the eye stimulate the function of washing and cleaning tears, and if there are drugs in these drops, they rapidly diffuse in a matter of minutes through the permeable structure of the lens.

The hydrogen peroxide treatment not only appears to harden the lens and increase its resistance to shatteringBAD ORIGINAL

7û 42863 ment, as mentioned above, from 1120 g / cm ^ to 1330 1400 g / cm ^, but also it opens and cleans the pores and microinterstices of the lens material through which the diffusion takes place " Therefore, the oxygenated water at the dilution of

3 % is a maintenance fluid that is used together. to a solution of 1% of baking soda, the latter having the effect of loosening the pores and softening the lens to facilitate its washing and to reduce the burst strength by 210 - 2Θ0 g / cm ^, and_;the first having the effect of counteracting this reduction to bring the lens to its maximum, of rigidity after washing. Surprisingly, it has been found that the aging of the lenses of the invention in normal use, for example their wearing and their maintenance, slightly increased the resistance to bursting of 140-210 g / cm 3. . Whether the lens was new with a burst strength of 1120 g / cm, or used with a resistance of 1400 g / cm ^, no difference was found in its corrective function or in its comfort.

The lenses of the present invention resist the sensitive dimensional changes which ordinarily occur upon application of different osmotic saline concentrations. The anisotropic swelling and retraction characteristics for a water content of 50 to 55% appear to constitute unique conditions for resisting dimensional variations of osmotic origin which could cause the lens to change in its position or to bend under i ¹ action of the normal movement of the eyelid, of a very bright illumination, of irritation to others.

If a lens is too rigid and insufficiently hydrated, which is the case with commercially available hydrophilic and highly crosslinked lenses, the inner curve. of the lens must be more pronounced than the curvature of the meat, with a spacing under the lens in the central region in order to be able to conform the lens to the cornea. It is this space which bends with each blink. The edge of the hydrophilic lens scrapes the cornea in its sensitive peripheral part.

Inadequate water content causes irritation and discomfort. Only by increasing the diameter of the lens

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42863 and by providing it with a very thin and flexible edge that could improve commercially available lenses, but the liquid permeability is still insufficient and the optical tolerance can never be as good as in the lenses of the invention the fact that such lenses are cut in the hard state with a greater degree of precision than the lenses of the prior art which are cut in the soft state. Surprisingly, there are no dimensional variations in the lenses of the invention for small variations in hydration, while such changes take place significantly with the lenses of the prior art. Consequently, the adjustment is flatter is better with the lenses of the invention, the optical correction is more precise; no appreciable movement takes place; and bending at the blinking is completely avoided.

In the lenses of the invention the elimination of flexion, the softer optical finish, the flatter corneal curvature, and the peripheral vesicle of tear fluid, make it possible to correct astigmatism in a much more satisfactory manner than with the lenses that are currently on the market.

The chemical composition of a hygroscopic lens of the invention, for example the essential content of PVP and HEMA, combined with the judicious process of polymerization in two stages to allow the precision of the running-in and the uniformity and the post-polymerization by irradiation and action of hydrogen peroxide, conferring adjustment precision, maximum resistance, elasticity and elastic recovery properties, all things essential to the comfort of the eye when the lens is worn for long periods.

Instead of the homopolymer constituted by polyvinylpyrrolidone, its short-chain alkylated derivatives can be used.

Namely:

- 3-nsethyl-l \ I-vinyl-2-pyrrolidone

- 4-methyl-N-vinyl-2-pyrrolidone.

- 3,3-dimethyl-i \ l-Vinyl-2 — pyrrolidone

- 4-ethyl-1M-vinyl — 2-pyrrolidone

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2g

- 5-m.ethyl-l \ l-vin.yl-2-pyrrolidone

- 5-ethyl-N-vinyl-2-pyrrolidone and others. These examples target all PVP having a short chain alkyl derivative in position 3, 4 or 5.

The composition also has utility as a liquid hygroscopic coating having strong adhesion to glass, plastics and metals after baking in two stages under the conditions indicated in FIG. 1. The pasty liquid can be applied at a thickness of 25 - 250 microns on a glass, flask or other to provide an anti-fog glass ”'suitable for cold drinks, the glass is therefore not subject to the - condensate! coming from outside. The coating can also be applied to automobile windshields to form an anti-fog · on the inside. The coating can also be applied to polycarbonate lenses used for ski goggles or for CR-39 (polycarbonate) plastic contact lenses.

The membrane composition can be poured in the manner of a desalination membrane and used to salify by reverse osmosis.

The membrane can be used as an antiseptic support strip for internal and external wounds, and, in this regard, another patent application by the same applicants relating to soft plastic bandages containing medicines for ophthalmological use, states that antibiotics, corticosteroids, antiseptics and disinfectants used in chemotherapy for infectious diseases.

In the treatment of the eye, these drugs incorporate pilocarpine, helladone alkaloids, ia dihenzyline, hydergin, methacholine, carbachol, bethanechol, sulfonamide and the like.

The inherent advantage of the precision of the lens of the invention is to prevent the liquid from accumulating behind the bandage when a drug support bandage is formed which extends over the sclera, under the eyelid, L 'edema ^' may appear with waterproof and hard acrylic bandages, is avoided, The active agents are not concentrated in the membranes

42863 of hydrated plastics of the invention, which would consequently cause an osmotic bulge, but are quickly diffused to bathe the affected part of the eye with the optimum concentrations for therapeutic efficacy. There is no dimensional change in the dressing when only saline and hypertonic drugs are applied to the eye, and this is a positive factor in the healing process.

The pasty composition can also be used to mold or coat an artificial eye, an organ or a prosthesis according to precise dimensions and without the risk of shrinking. In all these uses, the coating, the membrane, the molding, etc., can be cleaned with hydrogen peroxide after appropriate times.

The present invention is not limited to the embodiments described above, but by the content of the claims which follow.

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