JP2003504503A - Thermoformable ophthalmic lens - Google Patents

Abstract

  (57) [Summary] Melt-processable hydrogel block copolymers are made from hydrophilic and hydrophobic monomers, have sufficient internal association without cross-linking, and provide a dimensionally stable hydrogel at a maximum temperature of at least about 60 ° C. The polymer can be thermally processed into an ophthalmic lens and then hydrated to a hydrogel material. In some cases, the polymer can be treated before, during, or after hydration to form crosslinks.

Description

Detailed Description of the Invention

BACKGROUND OF THE INVENTION The present invention relates to the manufacture of ophthalmic devices by a molding process. More particularly, the invention relates to thermoformable hydrogel polymers and ophthalmic lenses, especially contact lenses, made by melt processing of the polymers.

The use of contact lenses not only for decoration but also as corrective ophthalmic lenses is well known. Various materials have been used in the manufacture of contact lenses, but these materials have been found to be less than ideal.

To be effective as a material for contact lenses, the material has certain important properties: (a) sufficient oxygen permeability, (b) good wettability with tear fluid,
(C) protein deposition resistance, (d) dehydration resistance (of hydrogel), (e) intended use (
Sufficient durability for (eg, disposable, long-term wear, etc.), (f) visual clarity,
(G) sufficient light transmission, (h) proper manufacturing cost, and (i) comfort
Must have

Various materials have some of these properties, but not all of them. For example, a contact lens made of a hydrophobic material often has good durability and oxygen permeability, but is not comfortable to wear. Some of the hydrophobic materials used to make contact lenses contain methacrylate and acrylate monomers containing large pendant groups containing substituted silicones, styrene monomers containing large substituents, etc. . However, they lack wettability and comfort.

On the other hand, a contact lens made of a hydrophilic material has wettability and oxygen permeability. Examples of commonly used hydrophilic monomers include hydroxyalkyl methacrylate, N-vinylpyrrolidone and polyvinyl alcohol.
However, these materials lack properties such as durability and dehydration resistance.

Accordingly, there is a need for ophthalmic lens materials that have only the advantages of these materials, excluding the disadvantages associated with both hydrophobic and hydrophilic materials. Considerable research effort has been concentrated on the development of such new materials. These novel materials are in the form of crosslinked hydrogel polymers with improved physical properties. Generally, a hydrogel polymer is considered to be a polymer having substantial hydrophilicity that is plasticized by absorbing moisture, and can be described as a soft and elastic moisture-containing gel. Materials that contain both hydrophilic and hydrophobic components can form hydrogels. In some cases, these materials can be considered amphipathic, exhibiting either hydrophilicity or hydrophobicity, depending on the conditions. In addition to the favorable physical properties found in hydrogel polymers, it is desirable to be able to efficiently manufacture and / or convert polymers into ophthalmic lenses.

Historically, contact lenses have been manufactured by at least one of three methods: lathe, centrifugal casting and cast molding. The lathe method cannot meet the demand for cheap, high volume, high speed manufacturing. Efforts to reduce the cost deficiencies inherent in the lathe process have resulted in a combined lathe and cast molding process. For example, a lens is cast on one side,
It can be manufactured by cutting the other surface with a lathe. Although this method is less expensive than the lathe method, it is less expensive than using only the casting method.

On the other hand, the centrifugal casting method often results in a lens having problems in optical quality and wearing condition. The reason is that the back surface of the lens is determined by centrifugal force rather than the requirements of an optimized lens type design.

[0009] In contrast, the casting method requires the use of two complementary molds. These molds are often disposable, and the cost of changing molds for each new lens accounts for a significant portion of the total cost of the final lens. In addition, the lenses produced by the casting method suffer from numerous quality defects during in situ polymerization due to shrinkage. For example, shrinkage may result in voids on the surface or the final product may not be compatible with the lens design. In the past, attempts have been made to improve the casting process by eliminating shrinkage. For example, Kindt-
Larsen, US Pat. No. 5,039,459, discloses replaceable diluents in a monomer mixture that are polymerized in a casting cup. However, in the case of a disposable casting cup, not only is the operation of replacing the replaceable diluent complicated, but there are also costs and troublesome problems. An advantage of the invention described below is that the casting cup and replaceable diluent are eliminated.

Therefore, there is room for improvement in developing suitable methods for producing lenses from novel polymers with improved properties. However, since cross-linked polymers are difficult to process, complete polymerization is usually done in the last molding step in the manufacture of contact lenses. The crosslinked polymer is a polymer in which polymer chains are bonded to each other to form a network structure. However, in the final molding / polymerization step, there are many quality control problems due to variations in the method. Therefore, it is desirable to use a method in which the polymerization is carried out before the final molding step.

Attempts have been made in the contact lens industry to manufacture contact lenses from polymethylmethacrylate (PMMA) using an injection molding process. PMMA lenses are hard and not oxygen permeable. That is, the quality of PMMA lenses is incomparable to that of hydrogel lenses. Thus, while injection molding methods such as those commonly used in the plastics industry are capable of high-speed, high-volume, high-quality, stable mass production, the above-mentioned important advantages of using these plastic manufacturing methods are important. There was no good contact lens material with properties.

Crosslinked hydrophilic polymers used as hydrogels, which may first be prepared in large batches, however, generally cannot be subsequently melt processed in an injection molding machine. Once crosslinked, this polymer cannot dissolve. Crosslinked polymers can only be molded and / or recycled under special circumstances. By partially or mildly shaping the crosslinked polymer, a thermosetting morphology with a further increased degree of crosslinking can be formed by a heat stabilization treatment. In addition, some crosslinks can be broken during treatment under heat and shear stress conditions. The cross-linked polymer is difficult to process, so it can be manufactured in large batches of stable quality, and processed with an injection molding machine at high speed and volume to produce soft contact lenses with desirable physical properties. There is a need for thermoformable or melt processable polymers that are capable of. The present invention not only addresses these needs, but provides other advantages that will be apparent from the description below.

DISCLOSURE OF THE INVENTION In a first embodiment, the present invention provides about 20-90% by weight of the total monomers of at least one hydrophilic monomer and about 5-80% by weight of the total monomers of at least 1.
A melt-fabricable hydrophilic polymer prepared by polymerizing a monomer containing a copolymerizable hydrophobic monomer of a species and not containing a crosslinking agent. In the unhydrated state, the polymer is melt processable at temperatures of 50-300 ° C. In the unhydrated state, the polymer is a hydrogel having a water content of about 35% to about 90% by weight of the total hydrated hydrogel. Moisture content is about 40
Is preferably about 80% by weight. The polymer is optically clear after being made into an ophthalmic lens and hydrated.

In a second embodiment, the invention comprises an ophthalmic lens comprising a polymer according to the first embodiment and sufficient water to be absorbed by the polymer into a hydrogel.

In a third embodiment of the present invention, a melt processable block copolymer is provided that is substantially free of chemical crosslinks. Non-crosslinked copolymers include blocks that self-separate into mutually immiscible phases. The main component in the copolymer contains blocks of hydrophilic units and the minor component contains blocks of hydrophobic units. At temperatures of at least about 80 ° C. and above, sufficient dissociation of the block of hydrophobic monomers allows the polymer to be heat processed into the desired shaped ophthalmic device. The non-crosslinked copolymer is
When hydrated to a hydrogel polymer, it has a sufficient amount of internal hydrophobic bonds within the hydrophobic region to be dimensionally stable when subjected to temperatures of at least about 60 ° C. and above.

In a fourth embodiment of the present invention, a monomer comprising at least one hydrophilic monomer and at least one hydrophobic monomer is copolymerized without forming substantial amounts of chemical crosslinks. Providing a polymer prepared by: increasing the temperature of the polymer to a temperature above its glass transition temperature or melting temperature; introducing the polymer into an ophthalmic lens mold; Forming a lens, solidifying the lens in a mold, removing the lens from the mold, and hydrating the lens in an aqueous salt solution to provide a hydrogel lens having a water content of about 35 to about 90% by weight. A method of manufacturing an ophthalmic lens, the method including:

In a fifth embodiment of the present invention, a step of forming a melt processable polymer by copolymerizing a hydrophilic monomer and a hydrophobic monomer in the presence of a monomer having a latent reactive functional group, Casting the polymer into a mold, molding the polymer into a lens, reacting latent functional groups to form covalent crosslinks in the polymer, and hydrating the lens to form a hydrogel material. And a step of forming the ophthalmic lens.

In a sixth embodiment of the invention, the steps of providing a solid, substantially non-crosslinked, crosslinkable polymer, introducing the polymer into the lens mold, and heat processing the polymer to form the lens mold. In-situ solidification, cross-linking the polymer in the lens mold shape, removing the lens from the mold, and hydrating the lens to give a water content above 35% by weight of the hydrated lens. And a step of forming a hydrogel having the same.

In a seventh embodiment of the present invention there is provided a melt processable graft copolymer which is substantially free of chemical crosslinks. Non-crosslinked copolymers include a backbone and grafted side chains that self-separate into mutually immiscible phases or regions. The main component in the copolymer is hydrophilic and the subcomponents are hydrophobic. At temperatures of at least about 80 ° C. or higher, sufficient dissociation of the regions containing the hydrophobic component allows the polymer to be heat processed into the desired shaped ophthalmic device. The uncrosslinked copolymer has a sufficient amount of internal hydrophobic bonds within the hydrophobic region to be dimensionally stable when hydrated to a hydrogel polymer and subjected to temperatures of at least about 60 ° C. and above. .

In an eighth embodiment of the present invention, a melt processable polymer is provided. The polymer comprises at least one of various repeating units. In the unhydrated state, the polymer is melt processable at temperatures of about 50-300 ° C. In the hydrated state, the polymer is a hydrogel having a water content of about 35 to about 90% by weight of the total hydrated hydrogel. The water content is preferably about 40 to about 80% by weight.
The polymer is optically clear after being made into an ophthalmic lens and hydrated.

[0021] Various embodiments of the present invention provide the advantages of materials capable of producing contact lenses that combine the excellent and important properties found in either hydrophilic or hydrophobic materials. It Further, various embodiments of the present invention provide materials that can be used to make contact lenses using reusable molds and utilizing high speed, high capacity thermoforming machines without the need for disposable molds. To be done. These and other advantages of the invention will be readily apparent from the following detailed description of the preferred embodiments of the invention.

Detailed Description of the Preferred Embodiments The present invention takes the form of several different embodiments. Some embodiments of the present invention provide about 20-90% by weight of at least one hydrophilic monomer and about 5-80% by weight.
Melt-fabricable hydrophilic polymers prepared by polymerizing monomers comprising at least one copolymerizable hydrophobic monomer of It is preferred that the polymer contains substantially no crosslinker.

In the unhydrated state, the hydrophilic polymer (ie, the xerogel) contains about 50
It can be melt processed or thermoformed at temperatures from about 300 ° C. Melt processing is a common method of processing polymers, examples of which include, but are not limited to, techniques such as thermoforming, injection molding, compression molding, resin transfer molding and extrusion molding. . Melt processing can be carried out in multiple steps, such as extruding the polymer once into an intermediate form and then compression molding into the final form. The xerogel is preferably melt processable at temperatures of about 80-250 ° C. More preferably, the xerogel is melt processable at temperatures of about 115 to about 200 ° C. At these temperatures, the viscosity of the polymer is about 100,000.
It is preferably less than 0 centipoise (cps), about 1,000 to 50,000.
More preferably, it is 0 cps. However, for some melt processing methods, such as compression molding, the work melt viscosity may be higher than the preferred viscosity range described above. The temperature at which the xerogel can be melt processed is above the glass transition temperature (T _g ) or melting temperature (T _m ) of the xerogel, but preferably below the temperature at which the xerogel degrades. Preferably the T _g of the xerogel is about 30 to 200 ° C., its creep stability is preferably at least about 30 minutes at about 120 ° C.. The preferred composition and parameters depend on the conditions of the manufacturing method of the lens and the required properties (eg oxygen permeability, visual clarity and water content).

In the hydrated state, a hydrophilic polymer has a water content (unless otherwise specified herein, the water content is expressed in wt% relative to the total weight of the hydrated lens). Of about 35 to about 90% by weight, and has an oxygen permeability (Dk) of about 8 to about 50.
Barrers (Dk units), forming hydrogels having a tear strength of greater than about 1 g / mm and a tensile modulus of about 20 to about 140 g / mm ² . The hydrogel polymer is preferably mechanically and dimensionally stable after being made into an ophthalmic lens, is optically transparent, and has a visible light transmittance of at least 90%. More preferably, the visible light transmittance is at least 95%, most preferably at least 99%.

The terms “mechanically stable” and “mechanical stability” as used herein maintain their consistent structural integrity when the polymer is hydrated into a hydrogel, It does not dissolve or become brittle enough to support its own hydrated weight. For example, brittleness or lack of mechanical stability can be demonstrated by the fact that the hydrogel is torn when the lens-sized portion of the hydrogel is picked up with tweezers. Of course, to be useful as an ophthalmic device, the hydrogel material must have a certain mechanical stability to withstand the normal forces associated with handling the device.

As used herein, the terms “dimensionally stable” and “dimensionally stable” refer to the material of a polymer hydrogel material processed into lenses, hydrated, and once the temperature is changed. It means that the change of the linear distance and / or the curvilinear distance is relatively uniform (ie isotropic) in all directions. That is, the change in lens diameter in one direction in the plane of the lens is not significantly greater than the change in another, and the curved shape of the lens is distorted to such an extent that it is no longer suitable for its intended use. Is not there.

A second embodiment of the invention is about 35-90 based on the total hydrated weight of the ophthalmic lens.
A lens comprising a polymer according to the first embodiment which contains a wt% water content, is an optically transparent and dimensionally stable hydrogel material. The hydrogel material of the ophthalmic lens preferably has substantially no covalent crosslinks. In other words, this means that the hydrogel, when dehydrated, has a sufficiently low crosslink density that it can be melt processed below the temperature at which it begins to deteriorate.

In a third embodiment of the present invention there is provided a melt processable block copolymer which is substantially free of chemical crosslinks. Non-crosslinked copolymers include blocks that self-separate into mutually immiscible phases. The main component in the copolymer contains blocks of hydrophilic units and the minor component contains blocks of hydrophobic units. The term "unit" is defined as a moiety that is joined to another moiety through at least two bonds to form a polymer. Monomers are converted into polymer units during the polymerization process. in this way,
Units are derived or formed from monomers.

At temperatures above at least about 80 ° C., sufficient dissociation of the blocks of hydrophobic units results in thermal processing of the polymer to form the desired shaped ophthalmic device. The non-crosslinked copolymers are mechanically stable when hydrated to hydrogel polymers, and dimensionally stable when the hydrogel is subjected to temperatures of at least about 60 ° C. or higher. It has a sufficient amount of internal hydrophobic bonds within the region of the hydrophobic unit.

The copolymer may then optionally be treated by chemically cross-linking the polymer to increase its dimensional stability after it has been formed into an ophthalmic device. Alternatively, to increase dimensional stability, the non-crosslinked polymer may optionally incorporate long side chains pendant from the polymer backbone that can form entangled and self-separating immiscible phases. Generally, these long side chains have a weight average molecular weight of about 300 to about 100,000. About 5 long side chains
It is preferred to have a weight average molecular weight of 00 to about 50,000. It is further preferred that the long side chains have a weight average molecular weight of about 1,000 to about 10,000.
For example, long chain polysiloxanes or poly (ethylene glycol) acrylates may be incorporated into the polymer for this purpose.

Furthermore, the ophthalmic device of the present invention may take the form of a contact lens, corneal implant or intraocular lens.

When the copolymer is an amorphous polymer without crystalline arrangement of the polymer chains, preferably the non-crosslinked copolymer is such that it does not become soft or sticky due to ambient temperature during handling, storage or transport. Sufficiently high glass transition temperature (T _g
) Should have. Furthermore, it is preferred that the T _g should be low enough so that it is not necessary to use a melt processing temperature close to the thermal decomposition temperature to prevent degradation during processing of the polymer. Thus, T _g good even -40~200 ℃.
For practical purposes, it is desirable for the T _{g to} be about 30 to about 200 ° C. It is preferred that the T _g is about 50-150 ° C. Even more preferably, the T _g is from about 60 to about 125 ° C. The T _g is the temperature below which a polymer is a hard glass, but above which it becomes a more flexible material.
For example, as the temperature of the polymer rises within the glass transition zone, the polymer may change from a rubbery material to a gum and eventually to a liquid.
T _g is the temperature at which the heat capacity of the polymer changes, and is represented by differential scanning calorimetry (DS).
Conveniently measured by C). Also, amorphous polymers do not show a sharp pattern when analyzed by X-ray diffractometry.

Similarly, when the copolymer is a crystalline polymer, the non-crosslinked copolymer has a sufficiently high melting temperature (T _m ) such that it does not become soft or sticky at ambient temperature during handling, storage or transport. Should have Furthermore, T _m should be an sufficiently low temperature such that it is not necessary to use a near melt processing temperature to the pyrolysis temperature to prevent degradation during processing of the polymer. So for practical purposes,
It is desirable for the polymer to have a T _m of about 100 ° C. or T _g (whichever is higher) to 250 ° C. Even more preferably, the T _m is at least about 5 ° C. above the steam sterilization temperature, which is usually about 120 ° C., and below about 250 ° C. Even more preferably, for practical work in various thermal processing equipment, the T _m is about 20 ° C. above the steam sterilization temperature, ie about 140 ° C., preferably below about 200 ° C. The T _m, is the temperature at which the crystal region is disturbed in the polymer. T _m is conveniently measured by DSC as the temperature at which there is an endothermic transition. Further, the crystalline polymer is
Shown are the patterns of rings, dots and arcs when analyzed by X-ray diffractometry.

In addition, the copolymer may include a combination of amorphous hydrophilic regions and crystalline hydrophobic regions. As the temperature of the semi-crystalline polymer rises within the glass transition zone, the polymer may change from glassy to elastomeric. Further increases in temperature can cause the material to turn liquid at its T _m . In the case of this copolymer, the T _{g of} the amorphous region and the T _{m of the} crystalline region are independently optimized, so that the benefits associated with the morphological and rheological attributes imparted to the copolymer by each region are related. You can get various advantages. Both T _g and T _m should be measurable by DSC.

There are certain advantages to optimizing T _g and T _m . It is expected that lowering T _g and T _m will allow the polymer to be melt processed at lower temperatures. In addition, this improves processability by extending the processable life of polymers, especially those containing heat-activated latent crosslinking functional groups. Furthermore, lowering the T _g is expected to minimize any cross-linking and / or curing of the polymer until it reaches the lens mold. T _g and T _m can be varied by adjusting the amount of hydrophobic units in the polymer. Also, increasing the amount of units containing flexible (long) side chains will decrease the T _{g of} the polymer. The crystallinity of a polymer can be reduced by incorporating asymmetric units or side chains into its structure. In the extreme example of this embodiment, T _g values well below room temperature are obtained.
Poly (alkyl acrylate) may indicate a T _g value of about -50 ° C., polysiloxanes may exhibit a T _g value of about -120 ° C.. By incorporating large amounts of units derived from alkyl acrylates or siloxanes throughout the material, the T _g
Values are expected to be lower than the temperature range.

The melt-processed hydrogel block copolymer according to this embodiment of the invention is
It preferably comprises the block copolymer of this embodiment and has a water content of greater than about 35% by weight of the hydrated lens. The water content is more preferably 35 to 90% by weight. It is even more preferable that the water content is 40 to 80% by weight. Desirably, the hydrogel block copolymer is optically transparent and has a refractive index of about 1.3 to 1.5, preferably about 1.4.

In a fourth embodiment of the invention, a monomer consisting of at least one hydrophilic monomer and at least one hydrophobic monomer is formed without forming a substantial amount of chemical crosslinks (ie , Less than about 0.25% by weight of crosslinker, preferably about 0%), providing a polymer prepared by copolymerization, introducing the polymer into a lens mold, and controlling the temperature of the polymer. Raising the temperature above the glass transition temperature and / or melting temperature, forming a lens, solidifying the lens in a mold, removing the lens from the mold, hydrating the lens in an aqueous solution Thereby forming a hydrogel lens having a water content of about 35 to 90% by weight of the hydrated lens.

The temperature of the polymer is raised before and / or after it is placed in the mold, depending on the type of processing equipment used. For example, in a typical thermoplastic injection molding machine, the temperature of the polymer is raised before it is placed in the mold. on the other hand,
In the case of compression molding or vacuum assisted molding, the polymer is processed into a thin film and probably does not need to be heated until it is cast into a mold. Depending on whether the polymer is amorphous or crystalline, its temperature is raised to a temperature above the T _g or T _{m of the} polymer, respectively. The desired range for T _g or T _m is consistent with the desired range described above in connection with the third embodiment of the invention.

In some cases, a release agent may be used to prevent the polymer from sticking to the mold.
A common mold release agent is food grade silicon. One of ordinary skill in the art can select any suitable commercially available mold release agent that is compatible with the polymeric materials of the present invention.

In a fifth embodiment of the present invention, a step of forming a melt processable polymer by copolymerizing a hydrophilic monomer and a hydrophobic monomer in the presence of a monomer having a latent reactive functional group, Then introducing the polymer into the mold, molding the polymer into the shape of a lens, reacting latent functional groups to form covalent crosslinks in the polymer, and hydrating the lens 35
And a step of obtaining a transparent hydrogel having a water content of more than wt.%.

The latent reaction of the functional groups may take place during or after molding and before or after the hydration step. To obtain sufficient latent cross-linking, it is desirable to use monomers having latent reactive functional groups in amounts up to about 40% by weight. It is preferred that all monomers be used in an amount of about 2 to about 25% by weight. From about 5 to about 20% by weight of such monomers
More preferably, it is used in an amount of

The amount of latently reactive functional group-containing units used to achieve a particular amount of crosslink density in this embodiment of the invention is the same as the crosslink density in a typical crosslink polymerization reaction of conventional hydrogel polymers. It is believed to be significantly higher than the amount of cross-linking agent used to obtain For example, in the polymerization of HEMA-based hydrogels, generally about 0.5
A suitable crosslink density is obtained by using wt% EGDMA. Perhaps the lower amount of EGDMA required is due to the mobility of the crosslinker in the polymerization mixture compared to the limited mobility of the pendant latent functional groups that are already tethered in place in the polymer chain. Is more efficient, or the monomer mixed with the non-crosslinked polymer of other embodiments of the present invention has limited access to the crosslinking site by the pendant latent functional groups. ing.

However, it has been observed that the efficiency of crosslinking according to the invention is poor, so that the crosslinked hydrogel was crosslinked by using conventional crosslinking agents during polymerization or by using the method of the invention. It is expected that one of ordinary skill in the art would be able to determine if this is the case. Simple analytical measurements should be able to provide the ratio of crosslink density per unit of crosslink functional groups. In the case of conventionally crosslinked hydrogels, this proportion is considered to be relatively large, and in the case of hydrogels crosslinked according to the invention, this proportion is believed to be relatively small.

In a sixth embodiment of the invention, providing a solid, substantially non-crosslinked, crosslinkable polymer, introducing the polymer into a lens mold, and heat processing (ie, heating) the polymer. By doing so, the ophthalmic lens is manufactured by a method including a step of solidifying in the lens mold, a step of crosslinking the polymer while maintaining the shape of the lens mold, and a step of removing the lens from the mold. Crosslinking may be initiated or activated by the heat supplied when the polymer is thermoprocessed. It is also possible to crosslink the polymer with a curing agent. The curing agent may be mixed with the polymer before it is cast into the mold, or it may be applied to the polymer after it has been molded into the shape of a lens. It is preferred to apply a release agent to the mold prior to introducing the polymer into the lens mold. The release agent prevents the lens from sticking to the surface of the mold,
The lens should be easy to remove. After removal, the lens can be hydrated to form a hydrogel polymer having a water content greater than 35% by weight of the hydrated lens.

In a variation of this sixth embodiment, the polymer is dosed in a heated mold with an agent capable of removing some of the polymer to form reactive species. For example, a suitable peroxide can be incorporated into this polymer. Heat decomposes the peroxide to remove hydrogen from the polymeric material, leaving the polymeric groups undergoing other reactions and crosslinking. If the polymer contains alkenyl groups, peroxy groups may add to the alkenyl groups to form polymer groups. The polymeric groups can be attached or added to other alkenyl groups to form crosslinks. Similar results should be obtained with azides or photosensitive compounds.

In a seventh embodiment of the present invention there is provided a melt processable graft copolymer that is substantially free of chemical crosslinks. Non-crosslinked copolymers include a backbone and grafted side chains that self-separate into mutually immiscible phases or regions. The main component in the copolymer is preferably hydrophilic and the subcomponents are preferably hydrophobic.
At temperatures of at least about 80 ° C. and above, sufficient dissociation of the region containing the hydrophobic component results in thermal processing of the polymer into the desired shaped ophthalmic device. The non-crosslinked copolymer has a sufficient amount of internal hydrophobic bonds within the hydrophobic region to be hydrated to a hydrogel polymer and dimensionally stable when subjected to temperatures of at least about 60 ° C. and above.

In an eighth embodiment of the present invention, a melt processable polymer is provided. The polymer comprises a unit of Formula I and Formula II below, where the unit is the moiety that forms a polymer by linking to the other moiety through at least two bonds. Different units do not necessarily bond with each other as shown in the drawings. further,
Multiple species according to each formula may be present in the polymer.

[0048]

[Chemical 2]

[0049]   In formula I, R¹Is H or CH₃And R²Is NR^FiveR⁶Or OR⁷And
, R^FiveIs H, CH₃, C₁~ C₅₀₀Alkyloxy, C₁~ C₅₀₀Alkenyloxy
, C₁~ C₅₀₀Alkylamino or C₁~ C₅₀₀Alkenylamino, R⁶Is
, H, CH₃, CH₂CH₃, C₁~ C₅₀₀Alkyloxy, C₁~ C₅₀₀Alkenyl
Oxy, C₁~ C₅₀₀Alkylamino or C₁~ C₅₀₀Alkenylamino,
R⁷Is H, C₁~ C₅₀₀Alkyloxy, C₁~ C₅₀₀Alkenyloxy, C₁~ C ₅₀₀ Alkylamino or C₁~ C₅₀₀It is alkenylamino.

In formula II, R ³ is H or CH ₃ and R ⁴ is C ₁ -C ₅₀₀ alkyl, C ₆ -C ₅₀₀ aryl, C (O) NR ⁸ R ⁹ or C (O) OR ^10. And R ⁸ is H,
CH _3, a C ₁ -C ₅₀₀ alkyl or C ₆ -C ₅₀₀ aryl, R ⁹ is an chain comprising C ₃ -C _{5 00} alkyl, C ₆ -C ₅₀₀ aryl, polysiloxane, or units of the formula II , And R ¹⁰ is H, C ₁ -C ₅₀₀ alkyl, and optionally — (CH ₂ CH ₂ N (C
H ₂ CH ₃ ) SO ₂ ) -C ₁ -C ₅₀₀ fluoroalkoxy containing a linking group or a chain containing units of formula II.

[0051]   Alkyl is a hydrocarbon chain which may be linear, branched or cyclic.
It Alkyloxy is, for example,-(CH₂CH (OH) CH₃) And- (CH ₂ CH₂OCH₂CH₃) Like a hydroxyl group or ether bond
An alkyl group in which at least one oxygen (O) is present. Alkylamino is an example
For example- (CH₂CH (NH₂) CH₃) And- (CH₂CH₂N (H) CH₂CH₃
), At least as an amino group, an amide group, an amino bond or an amide bond
Is also an alkyl group with one nitrogen (N) present. Alkenyl is straight-chain or
It may be branched or cyclic and contains at least one multiple carbon-carbon bond.
It is a hydrocarbon chain that has but is not aromatic. Alkenyloxy is, for example,-(
CH₂CH₂OCH₂CH = CHCH₃), Such as hydroxyl groups or ethers
An alkyl group in which at least one oxygen (O) is present as a bond. Archeni
Luamino is-(CH₂CH₂N (H) CH₂CH = CHCH₃)-Like
At least one nitrogen (as a mino, amido, amino or amido bond)
N) is an alkyl group present. Aryl means at least one aromatic carbon
Contains cyclic groups, optionally containing alkyl, alkoxy, or bonds
And optionally a halogen substituent. Polysiloxa
At least one of-(Si (CH₃) O) -containing units, and for example-
(CH₂CH₂CH₂O (Si (CH₃)₂) O)_xC (CH₃)₃), Archi
Alkenyl, alkoxy or alkyl or alkoxy end groups
Contained. Fluoroalkoxy is, for example,-(CH₂CH₂(CH₂)₇CF ₃ ) Is an alkyl group in which at least one fluorine (F) is present.

In the unhydrated state, the polymer can be melt processed at temperatures of about 50-300 ° C. In the hydrated state, the polymer is approximately 35% of the total hydrated hydrogel.
Is a hydrogel having a water content of about 90% by weight. It is preferred that the water content is from about 40 to about 80% by weight. The polymer becomes optically clear when cast into an ophthalmic lens and hydrated.

In practicing each of the various embodiments of the present invention, the polymer may be prepared by polymerizing at least one copolymerizable hydrophilic monomer and at least one hydrophobic monomer. Generally, such monomers are copolymerizable at the vinyl bond by radical initiated polymerization to form a single, unbranched polymeric backbone. It is preferable to use a vinyl monomer having a hydrophilic substituent or a hydrophobic substituent. A polymer prepared from only hydrophilic monomers exhibits hydrophilicity, whereas a polymer prepared from only hydrophobic monomers exhibits hydrophobicity. Hydrophilicity is
It is determined by measuring the contact angle formed between the surface of the polymer and the water droplets on this surface. This angle is measured using a goniometer. The contact angle of the hydrophilic polymer is preferably 0 to 90 °, more preferably 0 to 45 °. The contact angle of the hydrophobic polymer is preferably 91 to 180 °, and 1
More preferably, it is 35 to 180 °.

In general, for all embodiments disclosed herein, the hydrophilic monomer is N, N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), 1,2-dihydroxy-. Ethyl methacrylate, 2-
Hydroxyethyl acrylate (2-HEA), 2-ethoxyethyl methacrylate (EOEMA), N-vinylpyrrolidone (NVP), glycidyl methacrylate (GMA), glycidyl acrylate, glycerin monomethacrylate, glycerin monoacrylate, 2,3-dihydroxypropyl methacrylate (D
HPMA), 2,3-dihydroxypropyl acrylate (DHPA), 3-hydroxypropyl methacrylate, 3-hydroxypropyl acrylate, polyhydroxysucrylalkyl acrylate, acrylamide, acrylic acid, methacrylic acid, 4-hydroxybutyl methacrylate, 4-hydroxy. Butyl acrylate, N- (2-hydroxypropyl) methacrylamide, N-methylmethacrylamide, poly (ethylene glycol) monomethacrylate, poly (ethylene glycol) monomethyl ether monomethacryl, N-vinyl-N-methylacetamide, vinylmethyl sulfone , N-acryloylmorpholine, N-methacryloylmorpholine, N-methacryloylpiperidine, N-alkylacryloylamide, acid-functional molybdenum Such mer (and salts thereof), and may be selected from the group consisting of a combination thereof, but is not limited thereto. One or more hydrophilic monomers may be incorporated into the copolymerization mixture.

Preferred hydrophilic monomers are DMA, HEMA and NVP. More preferred hydrophilic monomers are DMA and HEMA.

If too little hydrophilic monomer is used, the water content and hardness of the resulting polymer will be inadequate, the lens may not be compatible with eye tissue and oxygen permeability may be reduced. . If too much hydrophilic monomer is used, the resulting polymer may not form a well-defined hydrogel. In a preferred embodiment, the hydrophilic monomer is used in an amount of about 20 to about 90% by weight of the total monomer mixture, preferably about 35 to about 80% by weight, more preferably about 45 to about 65% by weight. To be The exact amount depends on the monomer mixture selected, the processing conditions, the desired lens properties and the molecular weight of the monomers. One of ordinary skill in the art can optimize the exact amount of hydrophilic monomer used to achieve the desired polymer properties without undue experimentation based on the teachings contained herein.

Generally, for all of the embodiments disclosed herein, the hydrophobic monomer is selected from a wide range of monomers that are copolymerizable with the desired hydrophilic monomer. For example, the hydrophilic monomer and the hydrophobic monomer may both be vinyl monomers. Generally, such monomers are copolymerizable at the vinyl bond by radical initiated polymerization to form a single, unbranched polymeric backbone. Examples of suitable hydrophobic monomers for use in the present invention include methyl methacrylate and other alkylated alkyl acrylates, styrene, alkyl substituted styrenes such as t-butyl styrene, N-isopropylacrylamide (N-IPA).
, N- (t-butyl) acrylamide, N- (n-octyl) acrylamide,
N- (n-octadecyl) acrylamide, N-benzylmethacrylamide, N
Examples include, but are not limited to, substituted acrylamides and substituted methacrylamides such as -diphenylmethacrylamide, N, N-diphenylmethacrylamide, and the like, and combinations thereof.

The hydrophilic monomer is preferably copolymerized with the hydrophobic fluorinated monomer. The reason why such fluorinated monomers are preferred is that they are much more hydrophobic than non-fluorinated hydrophobic monomers. A preferable fluorinated monomer is 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate (FX-13).
, 2- (N-ethylperfluorooctanesulfonamide) ethyl methacrylate (FX-14), hexafluoroisopropyl acrylate, 1H, 1H, 2
H, 2H-heptadecafluorodecyl acrylate, pentafluorostyrene,
Examples include trifluoromethylstyrene, fluorostyrene, pentafluoroacrylate, pentafluoromethacrylate and the like. Preferred hydrophobic monomers are FX-13, FX-14 and 1H, 1H, 2H, 2H-heptadecafluorodecyl acrylate. The most preferred hydrophobic monomers are FX-13 and FX-14.

Further, the polymer can be prepared by copolymerizing a hydrophilic monomer with both a fluorinated hydrophobic monomer and a non-fluorinated hydrophobic monomer. However, it is preferable that the fluorinated hydrophobic monomer is not a silicon fluoride-containing monomer or a fluorinated polysiloxane monomer. Such monomers are often used to prepare materials for rigid gas permeable lenses, but often require surface treatments to obtain corneal compatible wetting. Therefore, it is not desirable to impart such properties to the hydrogel material.

Further, the polymer can be prepared using an amphipathic monomer. Such monomers have both hydrophilic and hydrophobic properties in different parts of the molecule and are well known in the art. Depending on which property is predominant, these monomers can be considered to be either hydrophilic or hydrophobic.

The total amount of hydrophobic monomers, ie monomers having hydrophobicity, is preferably such that sufficient bonds are obtained between the resulting hydrophobic units in the polymer chain.
The resulting "blocky copolymer" or "block copolymer" has mechanical and dimensional stability at storage temperature, use temperature, and preferably steam sterilization temperature. As used herein, the term "bulk copolymer" or "block copolymer", unless otherwise stated, is such that the degree of cohesion of the hydrophobic region forms a distinct phase distinct from the hydrophilic region. In a mathematical sense, it means a copolymer that is far more than is expected to be found in a polymer with a random statistical distribution with the same proportion of hydrophobic and hydrophilic units. The temperature of use is approximately that of the surface of the human eye, ie about 35 ° C. The storage temperature is
It can usually be at a temperature in the range of about 0 to 50 ° C., the duration is relatively unrestricted, months or years, with large temperature fluctuations. The heating or steam sterilization temperature is about 120 ° C. and has a relatively short duration, about 30 minutes.

Temporary pseudo-crosslinking properties are obtained by using a sufficient amount of hydrophobic monomers. In other words, hydrophobic units derived from hydrophobic monomers and dispersed throughout the polymer aggregate the moieties that are hydrophobic in nature of the polymer, and by internal hydrophobic bonds the material in the absence of covalent crosslinks. Has the ability to remain aggregated. This region may be amorphous or crystalline in structure. The need for this aggregation diminishes as the number of covalent crosslinks in the material increases. If too much hydrophobic monomer is used, the lens formed from the hydrogel may not be compatible with eye tissue, or may have segregation, haze, and leather-like properties. If too little hydrophobic monomer is used, the strength of the lens formed from the hydrogel may be inadequate, or the polymer may dissolve when the dry polymer is hydrated and no hydrogel may be formed.

In a preferred embodiment of the invention, the hydrophobic monomer is present in an amount of about 5 to about 80% by weight of the starting monomer mixture, preferably about 15 to about 50% by weight, more preferably about 20 to 40% by weight. Used in the amount of%. The exact amount depends on the monomer mixture selected, the processing conditions, the desired lens properties and the molecular weight of the monomers used. One of ordinary skill in the art can optimize the exact amount of hydrophobic monomer used to obtain the desired polymer properties without undue experimentation based on the teachings contained herein.

By increasing the amount of the same hydrophobic monomer used, the water content of the obtained hydrated polymer can be lowered. Alternatively, by using other different hydrophobic monomers such as methylmethacrylate or N-isopropylacrylamide,
The water absorption of the resulting swollen hydrogel polymer can be controlled.

Also, as mentioned above, the T _m and T _g of the polymer are reduced by increasing the amount of hydrophobic units or units with flexible side chains or units with an asymmetric structure incorporated into the polymer. Can be made. It should also be possible to change the T _g and / or T _m by changing the structure of the hydrophilic units. The following monomers: methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, 2-methoxyethyl acrylate, 2-ethoxyethyl acrylate, 2-propoxyethyl acrylate, 2-butoxyethyl acrylate, pentyl acrylate, hexyl acrylate, hexadecyl acrylate. , Octadecyl acrylate, poly (ethylene glycol) methyl ether acrylate, poly (ethylene glycol) alkyl ether acrylate, poly (ethylene glycol) phenyl ether acrylate, poly (ethylene glycol) monoacrylate, poly (propylene glycol) methyl ether acrylate, poly ( Propylene glycol) alkyl ether acrylate, poly (pro Glycol), poly (propylene glycol) mono acrylates and perfluoroalkyl ether acrylate are some examples of useful monomers to lower the T _g and / or the T _m of the polymer when converted into units. Further, methacrylate monomers corresponding to these acrylate monomers can be used. However, acrylates are preferred over methacrylates because polymers formed from acrylates are known to have lower T _g values than polymers formed from the corresponding methacrylates.

Polymers can also be prepared with small amounts of one or more high refractive index monomers to obtain a material having a desired refractive index of about 1.4 when hydrated. Due to the presence of the resulting high refractive index units in the polymer, the refractive index of the polymer is higher than that of a similar polymer without the high refractive index units. As the high refractive index monomer, pentabromophenyl methacrylate, pentachlorophenyl methacrylate, 2,4,6-tribromophenyl acrylate, 2-phenoxyethyl acrylate, 2-phenoxyethyl methacrylate, phenyl methacrylate, phenyl acrylate, benzyl methacrylate, benzyl acrylate. And so on. If fluorinated hydrophobic monomers are used, these aromatic monomers may need to offset the possible refractive index reduction in the resulting polymer due to the presence of fluorinated hydrophobic units.

In addition, the polymer may incorporate one or more units of UV absorbing functional groups. Such groups include, but are not limited to, 2-hydroxybenzophenone groups, benzotriazole groups, and combinations thereof. The presence of UV-absorbing units in a polymer results in a U of the polymer.
The V transmission is lower than the UV transmission of polymers that do not contain UV absorbing units.

The method of polymerization is not critical to the invention. A solution polymerization method, a bulk polymerization method or an emulsion polymerization method can be used. If desired, the size of the blocks can be adjusted using living radical (or controlled radical) polymerization techniques. The molecular weight can be controlled by using a chain transfer agent other than the reaction solvent. Most free radical initiators can optionally be used. Preferred initiators are Vazo® 64 (also known as AIBN) or Vaz commercially available from EI du Pont de Nemours & Co. of Wilmington, Del., USA.
o (registered trademark) 52. Alternatively, the polymer system may be designed to rely on other types of initiation and polymerization, such as thermal initiation, photoinitiation, cationic or anionic polymerization.

As mentioned above, at least one embodiment of the invention comprises a polymer having pendant functional groups capable of latent crosslinking. Indeed, latent crosslinking of polymers can be combined with most embodiments of the invention by several means. In general, covalent cross-linking in polymerized materials can be accomplished by (1) vulcanization, (2) radical reaction by ionizing radiation, (3) actinic radiation-induced reaction with photosensitive functional groups, or (4). It can be caused by a chemical reaction involving a labile functional group. The particular means chosen depends on the chemical system and the polymerization method used to make the polymer. Whatever cross-linking means is chosen, the cross-linkable functional groups must be latent. That is, the crosslinkable functional groups cannot act during the polymerization process but must begin to act during or after thermoforming the polymer into the desired ophthalmic lens shape. Of course, the cross-linking means chosen should not adversely alter the chemical or physical properties of the lens.

Photocrosslinking is one of the preferred means for latently crosslinking the polymer after melt processing it into the desired shape. The photocrosslinker, or photoinitiator, or photosensitive chromophore,
It can be incorporated into the polymer in several ways. For example, a vinyl monomer having a photosensitive functional group can be readily incorporated into a mixture of other vinyl monomers during the early stages of the polymerization process. Alternatively, the photosensitizing chromophore can be incorporated or blended into the polymer for subsequent crosslinking. Benzophenone is one of a class of such photosensitive chromophores that can be useful in crosslinking polymers. Some examples of the latent photocrosslinking agent that can be polymerized include 4- (2-acryloxyethoxy) -2-hydroxybenzophenone and 1,3-bis (4-benzoyl-3-hydroxyphenoxy) -2-propyl. Acrylate (cinnamyl methacrylate) and 2-cinnamoyloxyethyl acrylate are mentioned. Other latent photocrosslinkers that can be used in the present invention are J. Macromol.
Sci-Chem., A28 (9), pp. 925-947 (1991). For example,
1,2-diphenyl-2-hydroxy-2- (4-vinylphenyl) ethane-1
-One, 1-methoxy-1,2-diphenyl-2- (4-vinylphenyl) ethane-2-ol, 1,1-dimethoxy-1,2-diphenyl-2- (4-vinylphenyl) ethane-1 -One, 1,2-diphenyl-2-hydroxy-2- (4
-Vinylphenyl) ethane-1-one, 1,1-dimethoxy-1-phenyl-2
-(4-vinylphenyl) ethane-2-ol, 1-phenyl-2-hydroxy-2- (4-vinylphenyl) ethane-1-one, 2-hydroxy-2-methyl-1- (4-vinylphenyl) ) Propan-1-one, 2-hydroxy-2-methyl-1- (4-vinylphenyl) butan-1-one and 2-methyl-2-methoxy-1- (4-vinylphenyl) propan-1-one Is mentioned. After the melt processing step, the polymer can be cured by exposing the lens to UV, that is, the photosensitive functional groups can be reacted to cause crosslinking of the polymer. This UV curing can be done with the polymer dry or wet during or before hydration of the lens.

As an alternative to incorporating the photoinitiator into the polymer in the polymerization step,
It has been proposed to mix the melt processable polymer with a photoinitiator as shown below, either immediately before or during the melt processing step. These photoinitiators can undergo crosslinking after molding is complete. It is possible to photocrosslink the unhydrated polymer as well as the corresponding hydrated polymer. The photoinitiators shown below are those that can be used in the present invention and are commercially available from Ciba Specialty Chemicals Additives Division, Tarrytown, NY, USA. Trade names are shown in parentheses following the chemical name of each compound. 1-hydroxycyclohexyl phenyl ketone (Irgacure (registered trademark) 184), 2,2-dimethoxy-2-phenylacetophenone (Irgacure (registered trademark) 651), 2-hydroxy-2-methyl-1-phenylpropan-1-one (Darocur (registered trademark)
1173), 1-hydroxycyclohexyl phenyl ketone (Irgacure (registered trademark) 500), 2-methyl-1- [4- (methylthio) phenyl-2-morpholino] propan-1-one (Irgacure (registered trademark) 907), 2,4,6-Trimethylbenzoyldiphenylphosphine oxide (Darocur® 4265)
), 4- (2-hydroxyethoxy) phenyl- (2-hydroxypropyl) ketone (Irgacure® 2959), 2-benzyl-2-N, N-dimethylamino-1- (4-morpholinophenyl) 1 - butanone (eta ^{5-2,4-cyclopentadiene-1-yl)} [(1,2,3,4,5,6-eta) - (1-methylethyl) benzene] iron (+) hexafluorophosphate ( 1) (Irgacure (registered trademark) 369), 25% bis (2,6-dimethoxybenzoyl) -2,4,4-
Trimethylpentylphosphine oxide + 75% 2-hydroxy-2-methyl-
1-phenyl-propan-1-one (Irgacure® 261), and bis ((η ⁵ -2,4-cyclopentadien-1-yl) bis [2,6-difluoro-3- (1H-pyrrole -1-yl) phenyl] titanium (Irgacure ® 784DC).

It is also believed that in the hydration step of the method, the photoinitiator can be incorporated into the polymer after it has been molded into the shape of an ophthalmic lens. The hydration solution may contain a water-soluble photoinitiator that is incorporated into the polymer as it absorbs water and swells into a hydrogel. For example, crosslinking can be induced by immersing the polymer in a hydrogen peroxide solution. The crosslinking reaction can be accelerated by UV or heat. Alternatively, a reducing agent such as a ferrous salt (eg, iron (II) acetate, iron (II) chloride, iron (II) bromide)) can be added to the peroxide-containing hydration solution.

Another preferred means for effecting latent cross-linking of polymers is the secondary reaction of labile functional groups. Vinyl monomers having secondary reactive functional groups can be readily incorporated into the mixture of other vinyl monomers during the polymerization process. Peroxy, isocyanate, epoxy, hydroxyl, anhydride, and more specifically N-hydroxylmethyl functional groups are capable of latent crosslinking initiated by the heat used in the thermoforming process.

[0074]   As mentioned above, the incorporation of epoxy-containing units
A bridging functional group can be obtained. Free radical polymerization of epoxy-containing monomers
Can be polymerized by means of copolymerization when producing the polymer of the present invention.
You can These monomers containing epoxy functional groups include glycidyl
Methacrylate, glycidyl methacrylate + glycerin monomethacrylate^*
, Glycidyl acrylate, glycerin monovinyl benzyl ether, glycerin
Monovinyl ether, glycidyl acrylate + glycerin monoacrylate ^* , Glycidyl vinyl benzyl ether, glycidyl vinyl ether, allyl
Lysidyl ether, 1,2-epoxy-3-butene, 1,2-epoxy-4-pe
And 1,2-epoxy-5-hexene, but not limited to these.
Is not fixed (^*Is glycerin monomethacrylate or glycerin
It shows that the monoacrylate should accelerate the crosslinking reaction of the epoxy groups.
). Most epoxy (or glycidyl) monomers have diol impurities.
May be contained. This diol impurity, if present, is
Expected to promote / enhance bridge reaction.

Further, as mentioned above, functionalized acrylamides and functionalized methacrylamides, such as the monomers shown below, can provide latent cross-linking and may be incorporated into the polymerization mixture of the present invention. Examples of these monomers include acrylamide, N- (hydroxymethyl) acrylamide, N- (hydroxymethyl) methacrylamide, N- (isobutoxymethyl) acrylamide, N- (isobutoxymethyl) methacrylamide, and N- (2-hydroxy). Propyl) methacrylamide and N- (2-hydroxypropyl) acrylamide, but are not limited to.

Furthermore, as mentioned above, the polymerizable isocyanates are useful for providing units with latently crosslinkable groups. Examples of these isocyanate monomers include at least 2-isocyanate methacrylate and α, α-dimethyl-3-isopropenylbenzyl isocyanate.

Similarly, as mentioned above, anhydrides are also useful for latent crosslinking. Examples of the anhydride-containing monomer include at least 4-methacryloxyethyl trimellitic anhydride and itaconic anhydride.

In addition, units functionalized with hydroxyl groups can be introduced into the polymer using monomers such as those shown below. Crosslinking of the hydroxy-containing group in the polymer is carried out by polymerizing the polymer with diisocyanate (triisocyanate, tetraisocyanate, etc.), diepoxide (or triepoxide, tetraepoxide, etc.) or anhydride (or dianhydride). You can get started by processing at. Examples of hydroxyl group-containing monomers that can be used are at least 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 3-hydroxypropyl methacrylate, 3-hydroxypropyl acrylate, 4-hydroxybutyl methacrylate, 4-hydroxybutyl acrylate, and the like. , Glycerin monomethacrylate, glycerin monoacrylate, vinylbenzyl alcohol, various isomers thereof, glycerin methacrylate, and other functionally similar generalized structures.

Furthermore, the polymers may be mixed with materials such as diols, triols or diamines to enhance the crosslinking of these functional groups. Examples of curing agents for polymers containing pendant hydroxyl groups include at least 1,6-
Hexamethylene diisocyanate, toluene diisocyanate, methylene diphenyl diisocyanate, 4,4 ″ -methylenebis (N, N-diglycidylaniline), N, N-diglycidylaniline, N, N-diglycidylaniline, diglycidyl 1,2-cyclohexanedicarboxylate, diglycolic anhydride, ethylene glycol diglycidyl ether, 3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecarboxylate, glycerin triglycidyl ether, succinic anhydride, phthalic anhydride and anhydrous Pyromellitic acid is mentioned.
Examples of curing agents that can be used for the epoxy-containing polymer and the isocyanate-containing polymer include at least ethylene glycol, glycerin, 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, 1,2- Butanediol, 1,3-butanediol, pentanediol (and its various isomers), hexanediol (and its various isomers), 1,4-diaminobutane, 1
, 3-diaminobutane, butylamine (and various isomers thereof), bisphenol-A, ethanolamine, 3-amino-1-propanol, 1-amino-2-
Propanol, 3-amino-1-butanol, 4,4 ″ -methylenedianiline,
Water and sodium hydroxide are mentioned. Further, it is also possible to treat a lens molded through a thermoforming process using these curing agents.

Furthermore, crosslinking can be carried out by reacting the polymer with several reagents. For example, benzyl alcohol groups can be incorporated into the polymer by using vinyl benzyl alcohol in the polymerization process. The hydroxyl groups may be reacted with diisocyanates, diepoxides, dianhydrides or anhydrides, for example in an injection molding process. Heat or U if required
Additional V can be added to initiate the reaction that effects crosslinking.

Other similar examples of reactive latent crosslinking involve alkenyl (ie, olefinically unsaturated) pendant functional groups on the polymer. Pendant alkenyl functional groups can be incorporated into the copolymer by copolymerization requiring monomers such as dicyclopentenyl methacrylate, dicyclopentenyloxyethyl methacrylate, dicyclopentenyl acrylate and dicyclopentenyloxyethyl acrylate. The double bond in the dicyclopentenyl group is not involved in the polymerization but can be post-reacted (eg by oxidative crosslinking).

If the alkenyl-containing polymer is latently crosslinked in the molding process, the polymer is first crosslinked by mixing it with a peroxide. Several types of peroxy compounds can be used to facilitate crosslinking. Some examples are shown below. Acyl peroxides such as diacetyl peroxide and dibenzoyl peroxide Alkyl peroxides such as dicumyl peroxide and di-t-butyl peroxide Hydroperoxides such as t-butyl hydroperoxide and cumyl hydroperoxide t-butyl perbenzoate , T-butyl peracetate, and the United States,
Like Lupersol® 256 (2,5-dimethyl-2,5-di- (2-ethylhexanoylperoxyhexane) commercially available from Elf-Atochem North America, Inc. of Philadelphia, PA. Peresters; diperoxycarbonates such as OO-t-butyl O-isopropyl monoperoxycarbonate; ethyl-3,3-di (t-butylperoxy) butyrate and 2,2-
Di-peroxyketals such as di- (t-butylperoxy) butane Some of these peroxy compounds have been described by Polymer Engineering and Science, July,
1979, Vol. 19, No. 9, pp. 597-606.

Similarly, instead of activating the latent crosslinking reaction with heat, it is also possible to start activating the crosslinking reaction by moisture, acid or base catalysis or a combination thereof. Moisture activated cross-linking preferably incorporates at least one of alkoxysilane, silanol, acetoxysilane, silane or halosilane groups into the polymer. Alkoxysilanes, acetoxysilanes, silanes or halosilanes form silanols when exposed to moisture. Then, the silanols react with each other to form a siloxane bond. Therefore, polymer chains containing pendant silanol groups (or precursors) can bond together and form crosslinks by forming siloxane bonds. Thus, monomers prepared by copolymerizing such siloxane-functionalized monomers may be melt processed before the crosslinks are formed. Since it is activated by water, crosslinks are formed during the hydration of the polymer.

Cross-linking reactions involving organosilicon functional groups may also occur due to non-hydrolytic treatment. Halosilanes can form siloxane bonds by exposure to alkoxysilanes, metal oxides (eg, calcium oxide, magnesium oxide, zinc oxide, copper oxide, etc.) and alcohols + carboxylic acids. Alkoxysilanes can combine with each other to form a siloxane bond. Crosslinking and curing of silicones are well known (W. Noll, Chemistry and Technology of Silic.
See ones, Academic Press, Inc., London).

Further, the alkoxysilane can be silanol, acetoxysilane, carboxylic acid,
And form siloxane bonds when exposed to acids such as HCl. Crosslinking can be introduced into the melt-processed contact lens material using hydrolysis and non-hydrolysis reactions to form siloxane bonds. When water or other cross-linking initiator is mixed with a polymer containing silanol (or silanol precursor), a cross-linking reaction may start and gelation may occur in the lens mold under appropriate processing conditions. . Alternatively, gelation may occur by immersing the melt processed lens in a hydration solution. If desired, a catalyst may be added to the hydration solution.

The following are organosilicon monomers that may introduce moisture-induced crosslinking into the polymer by copolymerization with other monomers. These monomers contain carbon-carbon double bonds that participate in the initial polymerization reaction and silicon-containing groups that can be converted to siloxane bonds.

Examples of these monomers include methacryloxyethyltrimethoxysilane, methacryloxyethylmethyldimethoxysilane, methacryloxyethyldimethylmethoxysilane, methacryloxyethyltriethoxysilane, methacryloxyethylmethyldiethoxysilane, methacryloxyethyl. Dimethylethoxysilane, methacryloxyethyltrichlorosilane, methacryloxypropyltrimethoxysilane, methacryloxypropylmethyldimethoxysilane, methacryloxypropyldimethylmethoxysilane, methacryloxypropyltriethoxysilane, methacryloxypropylmethyldiethoxysilane, methacryloxypropyl Dimethylethoxysilane, methacryloxypropyl trichloro Examples include, but are not limited to, silane, styrylethyltrimethoxysilane and 3- (N-styrylmethyl-2-aminoethylamino) propyltrimethoxysilane hydrochloride.

In carrying out the latent crosslinking of the polymer, the crosslinking can be promoted by selecting a specific thermoforming method. For example, if only heat is required to initiate crosslinking, thermocompression molding of the uncrosslinked polymer film may be the most efficient processing method. On the other hand, when it is necessary to mix the non-crosslinked polymer with the curing agent, thermoplastic injection molding may be preferred. Similarly, in the general reaction injection molding (RIM) method, the non-crosslinked polymer can be dissolved in an organic solvent and mixed with the curing agent.

Polymers for this application, whether latently crosslinked or not, in addition to the usual properties of contact lenses, transparency, oxygen permeability, mechanical and geometric integrity,
It preferably has structural and dimensional stability in a sterilized state, biocompatibility, softness (comfort), and nontoxicity. Also, when used in injection molding equipment, the polymers have a low viscosity at high processing temperatures, are thermally stable without degradation at high temperatures, and have little or no chemical reaction during processing. It should preferably have special properties such as the short molding times exhibited.

Without being bound by any theory of operation, it is believed that suitable polymer systems according to at least one embodiment of the present invention aggregate in some way at room temperature. Heating the polymer to high processing temperatures causes these agglomerates to melt, resulting in a flowable, processable thermoplastic material. When the polymer cools to room temperature, the domains re-aggregate and retain their aggregates when the lens formed from the polymer hydrates into a swollen gel. The aggregate may be a crystalline domain having a high melting temperature T _m, an amorphous domain having a high glass transition temperature T _g , a highly hydrophobic domain, or a domain having a high degree of ionic interference or chain entanglement. These domains can remain structurally stable at low temperatures due to the cohesive forces between the segments of the polymer within those domains. For example, the high T _g blocks are known to have a high transition temperature, adhesion force at a temperature lower the T _g is strong. This may give the hydrogel sufficient structural integrity to withstand the osmotic forces that tend to pull the polymer apart.

Similarly, hydrophobic blocks may be formed due to the immiscibility of the long stretch of hydrophobic units in the copolymer with the majority of hydrophilic units. In particular, the fluorinated units are more immiscible with the hydrophilic domains than the corresponding hydrocarbon analogues, thus enhancing the cohesive forces within the hydrophobic block, ie, hydrophobic bonds. Therefore, the dimensional stability of hydrated hydrogels can be enhanced by lower amounts of fluorinated hydrophobic units than hydrocarbons incorporated into the polymer.

One preferred embodiment of the present invention is a transient, virtual, physical,
It is believed to utilize pseudo-crosslinks that are thermoreversible and not covalent. These agglomerates maintain the morphology of the polymer at cold and hydrated conditions, but melt and can be thermoformed at elevated temperatures. In contrast, prior art contact lens polymers generally rely on the formation of covalent crosslinks during polymerization, are invariant and cannot be thermoformed into the shape of the mold.

It is further contemplated that the present invention may take the form of several alternative embodiments. In certain other embodiments, block copolymers are used in which the blocks self-separate into mutually immiscible phases. The majority of the major components are, for example, poly (2-hydroxyethylmethacrylate), polyethylene oxide, polyacrylamide, polystyrene-maleic acid copolymers and Nakabayashi et al.
It consists of a block of known hydrophilic material such as zwitterionic phosphate containing units as described in 658,561. Such materials may be polar, cationic, anionic or zwitterionic and share only the property of being hydrophilic. Subcomponents consist of a rigid hydrophobic block having a glass transition temperature (T _g ) or melting temperature (T _m ) above the sterilization or use temperature but below the degradation temperature. Such high temperature hard blocks are exemplified by various nylons, perfluoroalkyl chains, perfluoroalkyl ether chains, polyacrylonitrile units, poly (ethylene terephthalate) units, polyvinylcarbazole units, polymeric liquid crystalline blocks suitable for all chemistries, etc. To be done.

The type of bond between the hard and soft blocks is not critical to the invention. However, the size of the domains of the hard block must be small enough to obtain optical transmission, which is an optical property, without causing significant light diffusion. The block copolymer can be in any form capable of causing this, ie the known diblock, triblock or multiblock. What is important is that optical transparency must be obtained in each case. Therefore, it is believed that the size of the domains of the hydrophobic block should be smaller than the wavelength of visible light, ie about 100 nm or less. Alternatively, when the hydrophilic block and the hydrophobic block have substantially the same refractive index, the domain size of the hydrophobic block may be larger than 100 nm and still maintain the optical transparency. be able to.

When processing these polymers in injection molding equipment, it is expected that the polymers will have the following properties: At elevated temperatures, the polymer flows as expected from the rheological behavior known by experience with block copolymers. The block melts at high temperature, resulting in a thermoformable material. It is preferred that no chemical reactions occur during the formation of the lens. Ophthalmic lenses are thin and the molding time is short because the material cures quickly. A heterogeneous structure is formed after molding and during solidification, but is stable at use and sterilization temperatures. This structure is also stable under the osmotic stress that occurs when hydrating the hydrophilic part of the system. The hydration and coagulation steps must give reproducible mechanical and optical results. Crosslinking must be controlled so that the fluidity of the material does not change significantly. Once the lens is formed, all crosslinks should have a reproducible effect on the lens and optics.

A second alternative form of the invention is known to be that block copolymer morphologies are known to form discontinuous patterns when constrained by thermodynamics and chain statistics and thermodynamic functions. Rely on facts. One of the well known patterns is the close-fitting (probably hexagonal but not necessarily) arrangement of cylinders embedded in a matrix phase. These cylinders have a minority component, ie about 3
It is preferably less than 0%. At about 70%, phase inversion occurs. The intermediate concentration form is still seen. The ability of the rod to align with the external field is well known. Extensional flow fields are particularly effective. The rod-shaped orientation in the XY plane along the principal director axis generally results in a highly anisotropic birefringent film. The size of the rod must be small enough to avoid light diffusion, i.e. not to impair the transmission of visible light. The lens as described represents an innovative bifocal lens for both eyes.

A third alternative form of the invention is the reaction of an isocyanate with a hydrophilic macromonomer to form a lens directly, for example in a steel mold cavity,
The use of polyurethane chemistry reduces work-molding time. Such chemical reactions are known to be fast and molding times are further shortened by using macromonomers. Since urethane bonds are known to be good oxygen permeators, a reduced water content can be applied. Until now, workers in the field of polyurethane lenses have lamented the lack of mechanical strength, but this is not recognized as a problem in today's era of disposable lenses. The above-described method can use a RIM (reaction injection molding) method in which a liquid reactive component is injected into a mold and reacted to form a final part. In the efficient manufacturing method, multiple RIs are placed on the rotary table.
An M-type installation, or "Lazy Susan" device, may be utilized.

The above-described embodiments of the present invention are suitable for utilizing high speed, high capacity screw extrusion thermoforming injection molding equipment, thermal stamping, vacuum assisted thermoforming, and RIM injection molding equipment. Direct molding or injection molding of a lens
) Placement and some imprints left on the final lens require some attention to possible discomfort to the lens wearer. There are several advanced methods that can be taken to prevent this effect. Hot runner molding is well known to processing engineers. A further effect that can be specified to minimize the gating effect is to rotate or vibrate the mold halves relative to each other when the lens body is in the liquid state. Irradiation of the ultrasonic beam to the gate area is an extension of the above concept. RIM technology may be used to reduce or eliminate gate traces.

In addition, other molding methods can be utilized for thermoformable or melt processable polymers prepared according to the present invention. Such methods include resin transfer molding, compression molding, extrusion molding, vacuum assisted plug thermoforming and stamp thermoforming. These methods can be applied by those skilled in the art to the manufacture of ophthalmic lenses.

The method of the present invention comprises the steps of making a thin film of polymeric material, inserting the film between heated mold halves, and halving the film. It is sandwiched between objects and the film is shaped into the shape of a contact lens precursor by applying sufficient force and heat for a sufficient time, opening the mold in half and opening the lens precursor into the mold. A method of making a hydrogel contact lens is included that includes the steps of removing from the half and forming the hydrogel contact lens by hydrating the lens precursor.

Another embodiment of the present invention comprises applying heat to melt the polymeric material, introducing the melted polymer into the cavity of the lens mold, and maintaining the melted polymer in the lens mold shape. , A step of solidifying in the lens mold, a step of opening the lens mold, and a step of taking out the lens from a half mold,
Forming a hydrogel contact lens by hydrating a lens precursor. Further, the lens precursor can be hydrated prior to removal from the mold halves.

Another embodiment of the invention is to dissolve the polymeric material in an organic solvent, mix the polymeric material with a curing agent, and throw the mixture of polymer and agent into the lens mold cavity. Holding the mixture in the cavity and causing a crosslinking reaction to solidify the reacted mixture into the shape of a lens mold, the step of opening the lens mold, and the step of taking out the lens from the mold half, Forming a hydrogel contact lens by hydrating the lens. In addition, the lens can be hydrated before removal from the mold halves.

The method has the advantage of using reusable types. Thus, the cost disadvantages of today's disposable plastic lens molds are eliminated. These reusable molds may be constructed of a transparent, durable material such as metal or quartz. Transparent molds are advantageous for methods where the polymer needs to be UV cured in the mold.

The method of making an ophthalmic lens of the present invention may be modified by those skilled in the art to allow additives to be added into or on the lens. These additives include colorants and handling tints, printed indici
Mention may be made of a), wetting and surface-treating agents, pharmaceuticals or other active ingredients. Further, the additive may be a plasticizer that facilitates processing of the polymer. The plasticizer may be reactive like glycerin or non-reactive like phthalate ester. Examples of phthalate esters that can be used include di (2-ethylhexyl) phthalate and diethyl phthalate. Depending on the nature of the additive,
It can be added during the initial polymerization, during melt processing, during or before the hydration of the polymer, can be added dissolved in the polymer, or can be mixed or blended with the dry powder polymer particles.

Therefore, one of the advantages of the present invention is the adaptability of the manufacturing method to the particular intended properties of the polymer and the processing constraints of the raw material of the finished ophthalmic lens. Therefore, one of a variety of melt processing methods is selected, depending on constraints, such as temperature limits, set by the particular additives that are desired to be incorporated into the lens.

Those skilled in the art will appreciate that the present invention may have broader applications than use in the manufacture of ophthalmic lenses. For example, a hydrogel polymer prepared according to the present invention or a method of the present invention may be a thin film wrapped dressing, a subcutaneous drug delivery device,
Or it may be useful for producing catheter coatings (by coextrusion).

The following examples show only some of the embodiments according to the present invention and do not limit the present invention. Amounts are in weight percent,% are weight percent and temperatures are expressed in degrees Celsius unless otherwise noted.

[0108] was synthesized in Example several new polymer revealed features. These evaluations are shown in Table 1. These polymers are composed of N, N-dimethylacrylamide and the following compound, a perfluoroacrylate known as FX-13, FX-1.
Prepared from one or more of perfluoromethacrylate known as 4, N-isopropylacrylamide (N-IPA) and methylmethacrylate (MMA). It was possible to melt press clear films from polymers prepared from these monomers. These films were transparent and formed hydrogels having a water content of about 55 to about 90% by weight of the total weight of the hydrated lens. The oxygen permeability, or Dk value, of these materials was about 45-31 barrers.

The dewatering behavior of the new polymers of Examples 1 to 4 was tested. The dewatering behavior of these materials is a trademark of Gentle Touch ^™ , a Wesley-based product in Des Plaines, Illinois, USA.
It was similar to the dehydration behavior of the netrafilcon contact lenses manufactured and sold by Jessen Corp.

Properties of some moldable materials are shown in Table 1. The hydrogel polymers of Table 1 were all dimensionally unstable at the high temperatures (eg 120 ° C.) found during autoclave sterilization, but do not subject the lenses to high temperatures, such as irradiation. Alternative sterilization methods can be utilized. Furthermore, if the contact lenses produced from these polymers are thermoformed in an aseptic state and then aseptically packaged while maintaining a sterile environment, a sterilization step may not be necessary.

Experimental Materials and Methods 2- (N-Ethylperfluorooctanesulfonamido) ethyl acrylate (FX-13) was supplied by 3M Corporation, St. Paul, Minn., USA. When stated to be purified herein, FX-13 was recrystallized twice with methanol before use. The following materials supplied by Aldrich Chemical Company: N, N-dimethylacrylamide, N-isopropylacrylamide, 2,2'-azobisisobutyronitrile (AIBN), 1,4-diaminobutane and 1,4-. Dioxane was used.

In Examples 1 to 4, the following general polymerization method was used. A round-bottomed flask was charged with the above-mentioned proportional amount of the monomer and the above-mentioned solvent of either toluene or dioxane. After the monomers were dissolved, AIBN as a polymerization initiator and a solvent were charged into the flask. The flask was immersed in a 60 ° C. oil bath. The reaction mixture was stirred under nitrogen for about 24 hours. Most of the solvent was removed from the reaction mixture by rotary evaporation. The viscous solution was poured into stirred diethyl ether to precipitate the polymer. The precipitated polymer was separated from diethyl ether and placed in a vacuum oven (65
Dry at ˜70 ° C., pressure less than about 0.1 mm Hg) for at least 24 hours.

The dried polymeric material was placed in a hydraulic laboratory carver press, Model C, commercially available from Carver Press, Inc., Wabash, Indiana, USA. The press was equipped with a heating table whose contact surface was covered with a sheet metal plate lined with aluminum foil. When indicated, a release agent (food grade silicone) was applied to the aluminum foil. The heating table is heated to a molding temperature of up to about 150 ° C. (unless otherwise noted) and the polymeric material of the examples below is applied to a thickness of 75 μm or 100.
Pressed to a transparent film that is μm. To obtain these thicknesses, the thickness should be 7
Brass spacer gaskets of 5 μm or 100 μm were used. Molding times were about 10 minutes, unless otherwise noted, and a force of about 7-9 metric tons was applied. The film was immersed in a 0.9% NaCl wash solution to form a clear hydrogel. The dimensional stability under these conditions was determined by stamping discs with a diameter of about 13 mm from the hydrogel and subjecting them to autoclave sterilization.

DSC measurements were made using a Dupont 910 Differential Scanning Calorimeter. DSC during the experiment
The cell was flushed with nitrogen. The sample was enclosed in an aluminum pan. The instrument was calibrated to the indium standard and an empty aluminum pan was used as a control.
The observed onset of melting of indium was 156.6 ° C +/- 0.5 ° C. The T _g value was taken as the inflection point (the number of scans after the second) in the thermogram. Thermogravimetric analysis (TGA) was performed using a Dupont 951 thermogravimetric analyzer in a nitrogen atmosphere. A heating rate of 10 ° C / min was used in the DSC and TGA experiments.

Whether the particular monomer is incorporated into the polymer by recording the FT-IR spectrum using a Biorad FTS 175 spectrometer, and
It was determined which composition should confirm the polymer structure. In the case of FT-IR analysis,
Samples are typically dissolved in chloroform and then cast on NaCl disks. The resulting film was then dried in a vacuum oven at about 80 ° C. Approximately 24 compression molded polymer films in 0.9% USP NaCl solution
Hydrogels were prepared by hydrating over time. The water content of the hydrogel was determined by an analytical balance with the aid of ATAGO's handheld refractometer and / or gravity. Calibration of the ATAGO refractometer is saturated NaCl
Checked with solution.

Oxygen permeability was measured polarographically using a Delta Scientific Products Model 2110 (DO) monitor or equivalent device. The refractive index is the Abbe refractometer (
Mark II model) and measured at 25 ° C.

The weight average molecular weight (M _w ) and number average molecular weight (M _n ) are perkin Elmer IS
Measured using S200 HPLC / SEC. ISS 200 is UV-
It was equipped with a VIS detector and a model 250 pump. 1m of ultra styragel column (1 x 10 ⁴ , 1 x 10 ³ , 5 x 10 ² A) connected in series
Used with eluent THF at a flow rate of L / min. A narrow molecular weight poly (methylmethacrylate) standard was used.

Elemental analysis was performed. Prior to elemental analysis, the sample was dried in a vacuum oven at 80 ° C. (about 25 inches Hg) for about 17 hours and then at 100-105 ° C. (about 25 inches Hg).
) And dried for about 48 hours. The weight percent of various monomers incorporated into polymer samples was calculated from the results of elemental analysis of sulfur and nitrogen. The estimated molecular weight of FX-13 was about 593. Unless otherwise indicated, the chemicals as received were used.

[0119]

[Table 1]

Detailed information about each of these polymers in Table 1 is provided in the Examples below.

Example 1 In this example, copolymerization of DMA, N-IPA and FX-14 was carried out in toluene. Initiators are not considered in the relative weight percentages of the monomers.

[0122]

[Chemical 3]

Polymer Properties a. FT-IR: spectra were consistent with materials containing functional groups of amide, ester and sulfonamide functional units. b. Glass transition temperature: 124 ° C. c. Pyrolysis: Significant weight loss started to occur at about 325 ° C. d. Molding properties: A transparent film was formed at @ 155 ° C. Molding time is about 1 in total
8 minutes e. Dimensional change: hydrated film area / dry film area, about 2.59 f. Dimensional stability of hydrogels during heat sterilization: Samples deformed during autoclaving. g. Refractive index: [email protected]° C. h. Dk = 35 barrers i. Water content: 75% j. Molecular weight: M _w = 88,000, M _w / M _n = 2.41

Example 2 In this example, the copolymerization of DMA, MMA and FX-14 was carried out in dioxane. Initiators are not considered in the relative weight percentages of the monomers.

[0125]

[Chemical 4]

Polymer Properties a. FT-IR: spectra were consistent with materials containing functional groups of amide, ester and sulfonamide functional units. b. Glass transition temperature: 104 ° C. c. Pyrolysis: Significant weight loss began to occur at about 315 ° C. d. Molding properties: A transparent film was formed at @ 160 ° C. Molding time is about 2 in total
For 2 minutes, the hydrogel was slightly hazy e. Dimensional change: Hydrated film area / Dry film area, about 1.9 f. Dimensional stability of hydrogels during heat sterilization: The sample deformed and became opaque during autoclaving. g. Refractive index: [email protected]° C. h. Dk = 35 barrers i. Water content: 72% j. Molecular weight: _Mw = 300,000, _Mw / _Mn = 2.70

Example 3 In this example, the copolymerization of DMA, MMA and FX-14 was carried out in toluene. Initiators are not considered in the relative weight percentages of the monomers.

[0128]

[Chemical 5]

Polymer Properties a. FT-IR: spectra were consistent with materials containing functional groups of amide, ester and sulfonamide functional units. b. Glass transition temperature: 102 ° C. c. Pyrolysis: Significant weight loss began to occur at about 315 ° C. d. Molding properties: A transparent film was formed at @ 160 ° C. Molding time is about 1 in total
6-20 minutes e. Dimensional change: hydrated film area / dry film area, about 2.48 f. Dimensional stability of hydrogels during heat sterilization: The sample deformed and became opaque during autoclaving. g. Refractive index: [email protected]° C. h. Dk = 35 barrers i. Water content: 70% j. Molecular weight: _Mw = 150,000, _Mw / _Mn = 2.6

Example 4 In this example, the copolymerization of DMA, MMA and FX-14 was carried out in toluene. Initiators are not considered in the relative weight percentages of the monomers.

[0131]

[Chemical 6]

Polymer Properties a. FT-IR: spectra were consistent with materials containing functional groups of amide, ester and sulfonamide functional units. b. Glass transition temperature: 103 ° C. c. Pyrolysis: Significant weight loss began to occur at about 315 ° C. d. Molding properties: A transparent film was formed at @ 160 ° C. Molding time is about 2 in total
2 minutes e. Dimensional change: Hydrated film area / Dry film area, about 2.76 f. Dimensional stability of hydrogels during heat sterilization: Samples deformed during autoclaving. g. Refractive index: [email protected]° C. h. Dk = 34 barrers i. Water content: 75% j. Molecular weight: _Mw = 78,000, _Mw / _Mn = 1.82

[0133]   The following method was used in Examples 5 and 6.

DSC measurements were made with a Dupont 2920 Differential Scanning Calorimeter. The DSC cell was flushed with nitrogen during the experiment. The sample was enclosed in an aluminum pan. An empty aluminum pan was used as a control. Thermogravimetric Analysis (TGA) is a Dupont 951
Performed by thermogravimetric analyzer. The performance of the device was checked with calcium oxalate monohydrate. A heating rate of 10 ° C./min was used for all DSC and TGA measurements.
FT-IR spectra were obtained with a Nicolet infrared spectrometer. Bruker ADVANCE DMX500
Proton NMR spectra were obtained on a high resolution digital NMR spectrometer. The water content was calculated using the weight of the dried and hydrated polymer film. Oxygen permeability was measured by polarography using a 2110 (DO) monitor or equivalent.

[0135] Example 5   In this example, the copolymerization of DMA and FX-13 was carried out.

[0136]

[Chemical 7]

A round bottom flask containing a magnetic stirrer was charged with N, N-dimethylacrylamide (20.
0765g), FX-13 (4.5208g) and 1,4-dioxane (11
0 mL). After the FX-13 was dissolved, 0.0408 g AIBN dissolved in 20 mL 1,4-dioxane was added to the reaction flask. The flask was fitted with a rubber septum and flushed with nitrogen for 30 minutes at room temperature. 1,4-dioxane 15mL
AIBN (0.083 g) dissolved in was added to the reaction mixture and the flask was immersed in a 60 ° C. oil bath. The reaction mixture was stirred under nitrogen for 24 hours.

After 24 hours, most of the dioxane was removed by rotary evaporation. About 30 mL of dioxane was added to the reaction mixture. The resulting solution was then poured into about 300 mL of stirred diethyl ether. The ether was decanted from the precipitated polymer and an additional 100 ml of fresh ether was poured into the polymer. The polymer was separated from ether and dried in a vacuum oven (65-70 ° C, pressure less than 0.1 mmHg).

After drying for 24 hours, a small sample was removed for FT-IR, DSC and NMR analysis. After drying for 48 hours, the polymer sample was 19.80.
It weighed 5 g. FT-IR (film cast on NaCl): 35
32, 2927, 1734, 1641, 1497, 1398, 1355, 1255, 1216, 1143, 1096, 1058, 92
6 cm ^-1 .

¹ H NMR (CDCl ₃ ): The spectrum showed evidence that both monomers were incorporated into the polymer. Polymer dried under reduced pressure for 24 hours (65-70
C) still showed a small amount of dioxane as evidenced by the singlet at 3.7 ppm.

Differential Scanning Calorimetry (DSC): The material showed a glass transition at 109 ° C. Significant weight loss began to occur during thermogravimetric analysis in nitrogen at a heating rate of 10 ° C / min near 325 ° C, which was indicative of the thermal decomposition temperature (decomposition temperature).

The film was hydrated with 0.9% NaCl aqueous solution. Hydration material has a water content of 84%
And a refractive index of 1.3545 (25.1 ° C.).

Film Forming: The samples used to form the film were dried for about 48 hours. A transparent film was formed at 155 to 160 ° C. in a carver press. The molding time was about 10 minutes. A transparent hydrogel was formed after immersing this material in 0.9% NaCl irrigation solution.

Polymer Properties a. Glass transition temperature: 109 ° C b. Decomposition at 10 ° C / min heating: significant weight loss started near 325 ° C. c. FT-IR: spectra were consistent with materials containing N, N-disubstituted amide, ester and sulfonamide functional groups. d. Proton NMR: The spectrum shows 2 due to the methyl group originating from the DMA unit.
． A small amount of residual 1,4-dioxane (singlet, 3.7 p) with a peak near 9 ppm.
pm). The resonance near 2.6-2.4 ppm is likely due to the ester methylene group derived from FX-13. The methylene proton in the polymer backbone is 1
． It occurred near 3ppm. e. Dk = 45 barrers f. Water content after (hydration in 0.9% NaCl): approx. 84% g. Dimensional change: Hydrated film area / Dry film area, about 3.57 h. Refractive index (R.I.) @ 25.1 ° C .: 1.3545 i. Molding characteristics: A transparent film was molded at 155 to 160 ° C. (molding time was about 10
It was for a minute). j. Molecular weight: _Mw = 100,000, _Mw / _Mn = 3.0

Examples 5 (a) -5 (j) Further testing was performed on the DMA / FX-13 copolymers. The copolymer is
The amount of DMA and FX-1 changed in reverse from 0 to 100% at the supply rate of about 10%.
Prepared according to 3. The physical properties of the obtained material were measured and are shown in Table 2 below. A typical procedure for preparing the polymer is as follows. DMA (15.149 g), FX-13 (6.063 g), VAZO64 in a 3-neck round bottom flask equipped with overhead stirrer, balloon and gas inlet.
(0.102 g) and toluene (150 mL) were added. The flask was immersed in a 60 ° C. water bath and depressurized until the contents of the flask began to boil. At this point the vacuum was discontinued and nitrogen was bleed into the flask until the 9 inch balloon was inflated. The reaction mixture was degassed and then backfilled with nitrogen three more times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture under nitrogen,
The mixture was stirred at 60 ° C for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporation and the resulting polymer was dissolved in about 100 mL THF. The THF solution was added to about 400 mL of stirring water (Milli Q). THF /
Separated from water mixture and placed in fresh Milli Q water. The polymer was then stirred with boiling Milli Q water for about 2 hours. The polymer was then separated from the water and washed several times with fresh Milli Q water in 200 mL portions. Place the polymer in a vacuum oven at 80
It was dried at about 48 hours (about 25 inches Hg). About 27.0 g of product was obtained.

[0146]

[Table 2]

Example 6 In this example, copolymerization of DMA, N-isopropylacrylamide and FX-13 was carried out.

[0148]

[Chemical 8]

In a round bottom flask containing a magnetic stirrer, N, N-dimethylacrylamide (8.0
198 g), N-isopropylacrylamide (2.0715 g), FX-13
(2.2625 g) and 1,4-dioxane (60 mL) were added. FX-1
3 dissolved, then AIBN 0.0408 dissolved in 20 mL 1,4-dioxane
g was added to the reaction flask. Attach the rubber septum to the flask and use nitrogen for 30 at room temperature.
Flashed for a minute. Immerse the reaction flask in a 60 ° C. oil bath and mix the reaction mixture with 24
Stir for hours.

After 24 hours, the reaction mixture became noticeably more viscous. The viscous solution was poured into 300 mL of stirring diethyl ether. The precipitated polymer was separated from diethyl ether and dried in a vacuum oven (65-70 ° C, pressure less than 0.1 mmHg).
. The polymer weighed 10.30 g after more than 24 hours in a vacuum oven.

Samples for FT-IR, NMR and DSC were dried for about 24 hours. FT
-IR (film cast on NaCl): 3488, 3313, 2929, 1734, 16
43, 1498, 1458, 1436, 1355, 1244, 1216, 1146, 1097, 1059 cm ^-1 .

¹ H NMR (CDCl ₃ ): The spectrum showed evidence that all three monomer components were incorporated into the polymer. For example, on a small scale of 3.9 to 3.8 ppm,
Broad peaks are probably due to N derived from N-isopropylacrylamide units.
This is because of -H proton. The large-scale peak centered around 2.67ppm is
It is from a methyl group derived from DMA. The peak centered at 2.40 ppm is probably due to ester methylene units originating from the FX-13 component. The spectrum showed a small amount of residual dioxane (acute singlet at 3.7 ppm).

Differential Scanning Calorimetry (DSC): The material showed a glass transition at 105 ° C. Significant weight loss began to occur near 300 ° C at a heating rate of 10 ° C / min during thermogravimetric analysis in nitrogen.

The film was hydrated with 0.9% NaCl irrigation solution. Hydration material is 80% water content
And a refractive index of 1.36 (25.1 ° C.).

Film Forming: The samples used to form the film were dried for about 28 hours. A transparent film was formed in a carver press at about 150 ° C. The molding time was about 9 minutes. A transparent hydrogel was formed after immersing this material in 0.9% NaCl irrigation solution.

Polymer Properties a. Glass transition temperature: 105 ° C b. Decomposition at 10 ° C / min heating: significant weight loss started near 300 ° C. c. FT-IR: spectra were consistent with materials containing functional groups of ester and sulfonamide and di- and monosubstituted amide units. d. Proton NMR: The spectrum showed a small amount of residual 1,4-dioxane (singlet, 3.7 ppm) with a peak at 2.89 ppm presumably due to the methyl groups originating from the DMA units. The resonance near 2.6-2.4 ppm appears to be due to the ester methylene group (from FX-13). Methylene protons in the polymer backbone were generated near 1.3 ppm. e. Dk = 44 barrers f. Water content after (hydration in 0.9% NaCl): approx. 80% g. Dimensional change: Hydrated film area / Dry film area, about 3.06 h. Refractive index (R.I.)[email protected]° C. i. Molding characteristics: A transparent film was molded at a molding temperature of 150 ° C. (molding time was about 9
It was for a minute). j. Molecular weight: _Mw = 110,000, _Mw / _Mn = 1.8

[0157]   The results of Examples 7-11 below are summarized in Table 4 below.

Example 7 In this example, copolymerization of DMA, GMA, MMA and FX-13 was carried out.

[0159]

[Chemical 9]

DMA (16.515 g), GMA (3.184 g), FX-13 (6.036 g) in a 3-neck round bottom flask equipped with an overhead stirrer (Teflon blade), balloon and gas inlet. , MMA (4.535 g), VA ZO52 (0.150 g) and toluene (150 mL) were charged. The flask was immersed in a 55 ° C. water bath and filled with nitrogen until the balloon (9 inch volume) was inflated. The reaction vessel was depressurized until the contents of the flask began to bubble. At this point the vacuum was discontinued and the flask was bleed with nitrogen until the 9 inch balloon was inflated. The reaction mixture was degassed and then backfilled with nitrogen three more times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture was stirred under nitrogen at 55 ° C. for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporation and the resulting viscous solution was diluted with about 50 mL THF. The THF solution was poured into about 500 mL of stirring hexane. The precipitated polymer was separated from the THF / hexane mixture and washed with 3 x 100 mL hexane. The sample was dried under reduced pressure (about 25 inches Hg) at about 70 ° C. for 72 hours to give 20.249 g of product. Samples were analyzed by FT-IR, DSC, TGA and GPC. FT-IR (film was cast from chloroform NaCl, peaks were selected): 33 24.7,3210.8,2932.6,1727.8,1682.7,1643.2,1497.7,1455.5,1397.8,13 54.9,1243.5,1214.1,1139.2,1058.1cm ^{- 1} . Differential Scanning Calorimetry: The polymer showed a glass transition temperature of 96 ° C. (second scan). Thermogravimetric analysis: When the sample was heated in nitrogen at 10 ° C / min, a significant weight loss began to occur near 359 ° C. Molecular weight: M _w = 111,300, M _w / M _n = 3.85.

Polymer Properties a. Monomer supply: DMA (54.5%) / FX-13 (19.9%) / MMA
(15%) / GMA (10.6%) (without considering the concentration of the initiator) b. 96 ° C. at T _g = DSC c. FT-IR is consistent with structure d. Decomposition temperature: TGA approx. 383 ° C

Molding Example 7A The polymer of Example 7 was compression molded at about 150 ° C. for about 20 minutes to obtain a transparent film having a T _{g of} about 96 ° C. The pressure was gradually increased to about 9-10 metric tons.
This material formed a clear hydrogel with a moisture content of 69% and Dk 44 barrers. In addition, it was stable to autoclave sterilization. Discs (13 mm) were cut from the hydrogel sheet to evaluate dimensional stability, then 0.0005%
It was sterilized in a package solution from Wesley Jessen, a borate buffered saline containing poloxamer. After the first sterilization, the diameter increased to 14 mm. However, the disc was still circular (preserved shape) and did not grow further after the second sterilization. The slight increase after initial sterilization is likely due to hydrolysis of residual epoxy groups. These results suggest that when compression molding is performed at 150 ° C. without adding a curing agent, gelation occurs in about 20 minutes or less.

Molding Example 7B The film obtained by compression molding the polymer of Example 7 in the presence of glycerin was somewhat soft and flexible. This material is about 20% milled polymer and
% (Wt%) glycerin to form a paste, followed by compression molding the paste at 150 ° C. for about 40 minutes to obtain a transparent film with a T _{g of} about 50-60 ° C. This value is about 46-56 ° C. below the glass transition temperature of compression molded samples without the addition of glycerin. In addition to being a hardener, glycerin also acts as a plasticizer. This property appears to allow glycerin to be used to optimize crosslink density and durability. GMA may contain a small amount of glycerin monomethacrylate. Such materials promote the crosslinking of epoxy groups.

The molded film formed a clear hydrogel with a water content of 70% and Dk 42 barrers. A 13 mm disc of hydrogel was expanded to 14 mm by heat sterilization. However, the shape was retained. The disc diameter and shape remained unchanged after the second sterilization.

Molding Example 7C The compression molded film of Example 7 was treated with a solution of a diamine curing agent (1,4-diaminobutane) to induce further crosslinking. As described above, poly (DMA / FX1
Treatment of 3 / MMA / GMA) at 150 ° C. causes some crosslinking. Films compression molded (150 ° C./about 20 minutes / about 9 metric tons) in the absence of glycerin were immersed in a 20% solution of 1,4-diaminobutane in isopropanol. After 3 minutes, the sample was removed from the diamine solution and then at 70 ° C. for 45 minutes, 13 minutes.
Heated at 5 ° C for 5 minutes. This material, T _g 112 ℃ (2 th scan) showed T _g 120 ° C. is between the third scan. These T _g 's were 16 and 24 ° C. higher than the T _g 's of compression molded films not treated with diamine. 112 ~
The increase in T _g to 120 ° C. is due to the reaction of amine groups and epoxy groups during DSC heating, causing further crosslinking. These results suggest that the diamine treated film is more crosslinked than the glycerin and non-glycerin treated polymers. The amine treated film formed a clear hydrogel with a water content of about 72%. The hydrogel shape remained intact after two sterilizations. The hydrogel diameter was reduced from 13 to 12 mm after two sterilization cycles.

The films described in "Molding Examples 7A-C" above formed transparent hydrogels with a water content of 69% -72%. The oxygen permeability of the hydrogels obtained by molding with or without glycerin was about 43 barrers.

Example 8 In this example, copolymerization of DMA, GMA, MMA and FX-14 was carried out.

[0168]

[Chemical 10]

DMA (16.507 g), GMA (3.018 g) in a 3-neck round bottom flask equipped with overhead stirrer (Teflon blade), balloon and gas inlet.
), FX-14 (6.084 g), MMA (4.614 g), VAZO52 (0
． 159 g) and toluene (150 mL) were added. The flask was immersed in a 55 ° C. water bath and filled with nitrogen until the balloon (9 inch volume) was inflated. The reaction flask was evacuated until the contents of the flask began to boil. At this point, stop the decompression,
The flask was flushed with nitrogen until a 9 inch volume balloon was inflated. The reaction mixture was degassed and then backfilled with nitrogen three more times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture was stirred under nitrogen at 55 ° C. for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporation and the resulting solid was diluted with about 50 mL THF. The THF solution was poured into about 500 mL of stirring hexane. The precipitated polymer was separated from the THF / hexane mixture and washed with 3 x 100 mL hexane. Sample under reduced pressure (about 25 inches Hg)
After drying at room temperature for 6 days, 23.894 g of the product was obtained. FT-I sample
It was analyzed by R, DSC, TGA and GPC. FT-IR (from chloroform to N
Film cast in aCl, selected peaks): 3438, 3266, 2984.1,
2947.1, 1731.7, 1644.8, 1504.0, 1455.2, 1397.4, 1357.2, 1243.5, 1143.9,
1059.9, 987.9, 909.7, 1397 cm ^-1 . Differential scanning calorimetry: The polymer showed a glass transition temperature of 98 ° C (second scan). Thermogravimetric analysis: sample in nitrogen, 10
Significant weight loss began to occur near 383 ° C when heated at ° C / min. Molecular weight:
_Mw = 118,300, _Mw / _Mn = 2.99.

Molding Example 8A A glycerin-free film was prepared by using the polymer of Example 8 in a carver press,
It was obtained by compression molding at 150 ° C. and applying food grade silicone as a release agent. The film was transparent and had a T _{g of} 91 ° C. This is about 7 ° C. below the T _g of the uncompressed polymer. The decrease in glass transition temperature is likely due to the plasticization caused by the release agent. The film prepared in the absence of glycerin had a water content of 71% and a Dk 38 barrers. Although the film was cross-linked, the hydrogel of this material deformed during autoclave sterilization. The shape changed from a 13 mm disc to an 16 × 12 mm ellipse. The results suggest that the materials are slightly cross-linked and that glycerin is an effective hardener for such materials. Furthermore, these results show that no hardener was added,
It shows that gelation occurs in 40 minutes or less.

Molding Example 8B The film obtained by compression molding the polymer of Example 8 in the presence of glycerin is somewhat soft and flexible. The glass transition temperature of the glycerin-containing material is about 72.
C (3rd scan). This value is about 26 ° C. below the glass transition temperature of the unmolded polymer without glycerin. This decrease in T _g is also due to glycerin, which acts as a plasticizer. The glycerin-containing material formed a clear hydrogel that was stable to autoclave sterilization. The hydrogel had a water content of 68% and a Dk of 43 barrers. These results also show that in the presence of glycerin,
When heated at about 150 ° C., this material exhibits gelling in less than 40 minutes.

[0172] Example 9   In this example, the copolymerization of DMA, GMA and FX-14 was used.

[0173]

[Chemical 11]

DMA (16.503 g), FX-14 (7.55 in a 3-neck round bottom flask equipped with an overhead stirrer (Teflon blade), balloon and gas inlet.
5 g), GMA (about 6.25 g), VAZO52 (0.124 g) and toluene (150 mL) were charged. The flask was immersed in a 55 ° C. water bath and filled with nitrogen until the balloon (9 inch volume) was inflated. The reaction vessel was evacuated until the contents of the flask began to boil. At this point the vacuum was discontinued and the flask was bleed with nitrogen until the 9 inch balloon was inflated. The reaction mixture was degassed and then backfilled with nitrogen three more times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture was stirred under nitrogen at 55 ° C. for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporation and the resulting viscous solution was TH
It was diluted with about 50 mL of F. The THF solution was poured into about 500 mL of stirring hexane. The precipitated polymer is separated from the THF / hexane mixture and washed with hexane 3x100.
Wash with mL. The sample was dried under vacuum (about 25 inches Hg) at room temperature for 20 hours. The sample is further dried under reduced pressure (about 25 inches Hg) at 70 ° C. for about 7 days,
18.386 g of product was obtained. Samples are FT-IR, DSC, TGA and G
It was analyzed by PC. FT-IR (film cast from chloroform to NaCl, selected peaks): 2933.5, 1728.4, 1643.2, 1496.0, 1396.2, 1355.5.
, 1244.5, 1212.9, 1137.3, 1059.9, 1000.2, 909.5 cm. Differential Scanning Calorimetry: The polymer showed a glass transition temperature of 91 ° C (second scan). Thermogravimetric analysis: When the sample was heated in nitrogen at 10 ° C / min, significant weight loss began to occur near 368 ° C. Molecular weight: M _w = 195,500, M _w / M _n = 4.06.

Polymer Properties a. Monomer supply: DMA (54.4%) / FX-14 (24.9%) / GMA
(20.6%) (without considering the concentration of the initiator) b. T _g = 91 ° C in DSC c. FT-IR is consistent with structure d. Decomposition temperature: about 368 ° C. by TGA e. Compression molding @ about 155 ° C for about 40 minutes f. A transparent, slightly yellow film was obtained g. The film was judged to be crosslinked due to lack of solubility in THF. h. The film formed a clear hydrogel i. Water content of hydrogel = 56% j. Refractive index (R.I.) = 1.41 k. Dk = 41 barrers l. Dimensional stability of hydrogels: Disc diameter before sterilization = 13 mm Diameter of disc after first sterilization = 14 mm Diameter of disc after second sterilization = 14 mm

Poly (DMA / FX-14 / GMA) was compression molded at about 150 ° C. for about 40 minutes to obtain a transparent film. The film was judged to be crosslinked due to lack of solubility in organic solvents. Upon hydration, a clear hydrogel was obtained which was stable to autoclave sterilization. The hydrogel has a water content of 56% and a Dk of 41 barre
had rs. The low water content of this material compared to the other samples is due to the high epoxy content of the unmolded polymer. A high epoxy content would result in a high crosslink density, which would result in a low water content hydrogel. The 13 mm disc of hydrogel was increased to 14 mm by sterilization (shape retained). The diameter did not increase further in the second sterilization cycle. The increase in diameter after the first sterilization cycle is likely due to hydrolysis of residual epoxy groups. The dimensional stability of the hydrogel and the insolubility of the zerogel in THF suggest that crosslinking during compression molding was successful.

The tensile properties of poly (DMA / FX-14 / GMA) were tested under various compression molding conditions. These conditions include compression molding at either 150 ° C or 160 ° C for 20 or 40 minutes with or without the addition of glycerin to the polymer prior to molding. Lloyd Instruments Mode for measuring tensile properties
l 500 Tensile Tester (available from Chartillon Greensboro, NC, USA) was used. Tensile tester is operated by 5 Newton load cells, pulling speed is 1
It was set to 00 mm / min. The results are shown in Table 3 below.

[0178]

[Table 3]

Example 10 In this example, copolymerization of DMA, NHMA, NHMA, MMA and FX-14 was performed.

[0180]

[Chemical 12]

DMA (16.519 g), FX-14 (6.10) in a 3-neck round bottom flask equipped with an overhead stirrer (Teflon blade), balloon and gas inlet.
3 g), MMA (4.517 g), NHMA (48% solution in water 6.267 g),
VAZO 52 (0.142 g) and THF (150 mL) were added. Flask 5
Immerse in a 5 ° C. water bath and fill with nitrogen until the balloon (9 inch volume) inflated.
The reaction vessel was evacuated until the contents of the flask began to boil. At this point the vacuum was discontinued and nitrogen was bleed into the flask until the 9 inch balloon was inflated.
The reaction mixture was degassed and then backfilled with nitrogen three more times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture under nitrogen, 5
Stir at 5 ° C. for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporator and the resulting solid was dissolved in 50 mL THF. The THF solution was added to 500 mL of stirring hexane. The precipitated polymer was separated from the THF / hexane mixture and washed with 3 x 100 mL hexane. Sample under vacuum (~ 25 inches
Hg) and dried at about 65 ° C. for about 23 hours. The sample was further dried under reduced pressure for about 6 days. About 30 g of product was obtained. Samples FT-IR, DSC and TGA
And analyzed by GPC. FT-IR (film cast from chloroform to NaCl, selected peaks): 3318.2, 2933.5, 1727.76, 1638.7, 1498.
3, 1397.8, 1355.5, 1243.6, 1213.5, 1139.2, 1056.6 cm ^-1 . Differential scanning calorimetry:
The polymer showed a glass transition temperature of 117 ° C. (second scan). Thermogravimetric analysis: When the sample was heated in nitrogen at 10 ° C / min, a significant weight loss began to occur near 380 ° C. Molecular weight (based on all GPC peaks): M _w = 65,20
0, M _w / M _n = 5.5.

Polymer Properties a. Approximate monomer feed: DMA (49.2%) / FX-14 (18.2%) /
MMA (13.5%) / NHMA (18.7%) b. T _g = 117 ° C. in DSC c. FT-IR is consistent with structure d. Decomposition temperature: about 380 ° C. by TGA e. Compression molding @ about 160 ° C for about 30 minutes f. A transparent, slightly yellow film was obtained g. The film was judged to be crosslinked due to lack of solubility in THF. h. The film formed a clear hydrogel i. Water content of hydrogel = 76% j. Refractive index (R.I.) = 1.37 k. Dk = 54 barrers (standard deviation = 7.9) l. Dimensional stability of hydrogels: Disc diameter before sterilization = 13 mm Diameter of disc after first sterilization = 14 mm Diameter of disc after second sterilization = 14 mm

Poly (DMA / FX-14 / MMA / NHMA) was compression molded to obtain a transparent film. The film was judged to be crosslinked due to lack of solubility in organic solvents. Upon hydration, a clear hydrogel was obtained which was stable to autoclave sterilization. The hydrogel had a water content of 76% and a Dk of about 53 barrers.

Example 11 In this example, copolymerization of DMA, NHMA, MMA and FX-14 was performed.

DMA (13.430 g), FX-14 (6.24) in a 3-neck round bottom flask equipped with an overhead stirrer (Teflon blade), balloon and gas inlet.
1 g), MMA (4.540 g), NHMA (48% solution in water 12.508 g)
, VAZO 52 (0.149 g) and THF (150 mL) were added. The flask was immersed in a 55 ° C. water bath and filled with nitrogen until the balloon (9 inch volume) was inflated. The reaction vessel was evacuated until the contents of the flask began to boil. At this point the vacuum was discontinued and nitrogen was bleed into the flask until the 9 inch balloon was inflated. The reaction mixture was degassed and then backfilled with nitrogen three more times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture under nitrogen,
The mixture was stirred at 55 ° C for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporator and the resulting solid was dissolved in 50 mL THF. The THF solution was added to about 500 mL of stirring hexane. The precipitated polymer was separated from the THF / hexane mixture and washed with 3 x 100 mL hexane. The sample was dried under reduced pressure (about 25 inches Hg) at about 65 ° C. for 15 hours. The sample was further dried under vacuum at room temperature for 6 days. About 28 g of product was obtained. After drying, the sample became insoluble in organic solvents. The polymer appeared to be prematurely crosslinked. Sample DSC
And analyzed by TGA.

[0186]

[Table 4]

Example 12 In this example, copolymerization of DMA, FX-13, GMA and RA (alkyl acrylate) was carried out. The purpose of this example was to show that the use of flexible side chains (R) incorporated into the polymer reduces the glass transition temperature. DMA, FX-13 and GMA were copolymerized with various alkyl acrylates (RA) according to the general polymerization procedure of the previous examples. R was selected from n-butyl, sec-butyl, n-hexyl and n-butoxyethyl groups. Table 5 below shows the T _g results of various polymers measured by DSC. These numbers indicate that the non-hydrated polymer can be modified by modifying the monomer side chains. It is well known that flexible side groups reduce the glass transition temperature of polymers by acting as internal diluents. This reduces mutual friction between chains (LH Sperling, Introduction to Polymer Science, 2nd edition, John
See Wiley & Sons). Low T _g polymers are expected to have long melt processing times.

[0188]

[Table 5]

The polymer of Example 12D was compression molded in a Carver press at about 160 ° C. for about 40 minutes. A soft and transparent film was obtained. The film was judged to be crosslinked due to lack of solubility in THF. Upon hydration, the film formed a clear hydrogel. The water content was about 75% by weight, based on the total weight of the hydrated film. Next, the hydrated film was subjected to a heat sterilization cycle to determine the dimensional stability under heat sterilization conditions. Both the diameter (about 13 mm) and the shape of the film were retained after being subjected to sterilization.

The polymer of Example 12D was also compression molded at low temperature. In the first example, the polymer was molded at 110 ° C. for about 12 minutes. A transparent and flexible film was obtained. The film was judged to be uncrosslinked due to its solubility in THF.
Upon hydration, the film formed a clear hydrogel with a water content of about 76% by weight. In the second example, after mixing about 6% by weight glycerin, the polymer was molded at 100 ° C. for about 20 minutes. A very soft and transparent film was obtained. The film is THF
It was determined that it was not crosslinked due to its solubility in. Upon hydration, the film formed a clear hydrogel.

Example 13 In this example, copolymerization of DMA, FX-13, GMA and RA (alkyl acrylate) was carried out. The purpose of this example was to further illustrate the effect of the flexible side chains (R) on the properties of the copolymer and the resulting hydrogel. DMA, FX-13 and GMA were copolymerized with various alkyl acrylates (RA) according to the general polymerization procedure of the previous examples. R is n-butyl, iso-
Selected from butyl, n-hexyl, n-butoxyethyl and n-octadecyl groups.

The following general polymerization conditions were used. A round bottom flask was charged with the amounts of monomer described, Vazo 52 initiator (monomer + about 0.5 wt% relative to initiator) and toluene. A rough estimate of the relative monomer content in the reaction is DMA (5
4.5% by weight), FX-13 (20% by weight), GMA (10.0% by weight), RA
(15% by weight). After the monomers had dissolved, the flask was immersed in a 55 ° C. water bath and purged with nitrogen. The reaction mixture was then stirred under nitrogen for about 24 hours. The solvent was removed from the reaction mixture by rotary evaporation. The obtained sample was diluted with 75 mL of THF. The viscous solution was poured into stirring hexane to precipitate the polymer. The precipitated polymer was separated from hexane and placed in a vacuum oven (65-65).
It was dried at 70 ° C. and a pressure of 0.1 mmHg or less) for at least 24 hours. The FT-IR spectrum of each polymer was consistent with the material containing amide, ester and sulfonamide functional units. The results of the characterization of the dry copolymer and hydrogel are summarized in Table 6 below.

N-Butoxyethyl acrylate (BEA) was used as the alkyl acrylate in the polymer of Example 13A. The copolymer was molded in a carver press to obtain a transparent, flexible film. When molded at 100 ° C. for 20 minutes, the film was uncrosslinked as shown by its solubility in organic solvents. Molded at 150 ° C. or 160 ° C. produced a crosslinked film, which was hydrated to produce a hydrogel.

N-Hexyl acrylate (HA) was used as the alkyl acrylate in the polymer of Example 13B. The copolymer was molded in a carver press to obtain a transparent, flexible film. Molded at 160 ° C. or 180 ° C. produced a crosslinked film which was hydrated to produce a translucent hydrogel. Glycerin about 6
The copolymer sample mixed with wt% produced a clear film, which was smooth and very flexible. Hydration of these films results in hydrogels that are optically clear and stable to heat sterilization.

N-Butyl acrylate (BA) was used as the alkyl acrylate in the polymer of Example 13C. The copolymer was molded in a carver press to obtain a transparent, flexible film. Molding at 160 ° C. for 20-40 minutes produced a clear, slightly brittle crosslinked film. Molding at 180 ° C. for 10 minutes produced a transparent, flexible film. The film pressed at either 160 ° C or 180 ° C was hydrated to give a clear hydrogel. Also, this copolymer is
About 6 wt% glycerin can be mixed prior to compression molding at either 0 ° C or 180 ° C. Hydration of these films resulted in clear hydrogels with lower water content and mechanical stability than those formed from copolymers without glycerin.

The polymer of Example 13D used iso-butyl acrylate (IBA) as the alkyl acrylate. The copolymer was molded in a carver press to obtain a transparent, flexible film. Molded at 160 ° C. or 180 ° C. produced a crosslinked film, which was hydrated to produce a clear hydrogel. These hydrogels became cloudy and adhesive when heat sterilized. The copolymer sample mixed with about 6% by weight of glycerin produced a clear film, which was smooth and flexible. Hydration of these films resulted in hydrogels that were optically clear both before and after heat sterilization.

N-Octadecyl acrylate (ODA) was used as the alkyl acrylate for the polymer of Example 13E. The copolymer was molded in a carver press to obtain a transparent, flexible film. When cast at 100 ° C. for 12 minutes, the film was uncrosslinked as shown by its solubility in organic solvents. Molded at 160 ° C. or 175 ° C. produced a crosslinked film, which was hydrated to produce a hydrogel. The polymeric hydrogels molded at 175 ° C were slightly cloudy upon heat sterilization, while the polymeric hydrogels molded at 160 ° C remained transparent.

[0198]

[Table 6]

Example 14 In this example, a two-step molding process was performed using the copolymers of Examples 13A, 13B, 13C and 13D. Each of these copolymers was converted into an uncrosslinked sheet when molded in a Carver press at 90 ° C. for 20 minutes. THF
Solubility tests on the films showed that films formed under these conditions were not chemically crosslinked. The same copolymer also formed an uncrosslinked sheet when mixed with about 6% by weight glycerin before molding under these conditions. The molded film test piece caused a crosslinking reaction when placed in a 200 ° C. air circulation oven. Gelation was monitored by removing strips of film at specific intervals and measuring their solubility in THF. Gelation of these copolymers occurred at 200 ° C. for about 3-5 minutes. Gelation occurred without glycerin, but the presence of glycerin appears to enhance the gelling process. In the absence of glycerin, the copolymer of Example 13A was substantially crosslinked after 5-7 minutes at 160 ° C and 10 minutes at 145 ° C.

Example 15 In this example, the copolymer of Example 13E was used to perform a two step molding process. Copolymer mixed with 5% by weight of glycerin
When it was molded at 70 ° C. for 20 minutes, it was converted into a crosslinked sheet. Solubility tests in THF showed that films cast under these conditions were chemically crosslinked. A disk with a diameter of 12 mm is cut from the formed sheet, and 170 ° C in a carver press
Further molding was carried out for 30 minutes at a load of 0.5 metric tons. Hydration of this sample produced a lens-like object.

This indicates that the partially cured polymer sheet or disc can be formed into a lens-like object. Weak cross-linking can carry out further processes during which unreacted latent cross-linking sites may react, producing objects with increased cross-link density than partially cured polymers. .

Example 16 In this example, copolymerization of DMA, FX-14, MMA and NIBMA was carried out. The purpose of this example was to show the use of functionalized acrylamide monomers as latent crosslinkers. Following the general polymerization procedure of the previous example, DMA (
55% by weight), FX-14 (20% by weight) and MMA (15% by weight) and NIB
It was copolymerized with about 10% by weight of MA (N-isobutoxymethylacrylamide).
NIBMA acts as a latent crosslinker. The obtained polymer is heated at 160 ° C. about 40
It was compression molded for a minute to obtain a transparent and flexible film. The film was determined to be crosslinked due to insolubility in THF. Upon hydration, the film formed a hydrogel with a water content of about 73%. Some deformation occurred in the hydrogel during the heat sterilization process.

Example 17 In this example, copolymerization of DMA, FX-14, MMA and DCPMA (dicyclopentyl methacrylate) was carried out. The purpose of this example is to show the use of an alkenyl-containing methacrylate monomer, which is incorporated into the polymer to add peroxide prior to compression molding to cause latent crosslinking. 10. Following the general polymerization procedure of the previous example, DMA (54.5 wt%), FX-14 (19.9 wt%) and MMA (14.9 wt%) and DCPMA (dicyclopentenyl methacrylate) 10. 2% by weight was copolymerized. A polymer with a T _{g of} 71 ° C. was obtained.

The polymer was subjected to 3 separate molding experiments. In the first example, the polymer is 155
It was compression molded for about 20 minutes at 0 ° C. to obtain a transparent, yellowish film. The film dissolved in organic solvent and was shown to be uncrosslinked. Upon hydration, the film formed a slightly hazy hydrogel with a water content of about 71% by weight. The hydrogel was not dimensionally stable under heat sterilization conditions. Under such conditions, the hydrogel shape changed from circular to elliptical.

In the second example, the polymer was mixed with about 6% by weight peroxide. Mixing was accomplished by dissolving the polymer in an organic solvent such as THF, acetone or chloroform and then mixing with peroxide. The solvent was then evaporated and the resulting dry polymer / peroxide blend was compression molded at 155 ° C. for about 22 minutes to give a clear, yellowish film. The film was not soluble in organic solvents and was shown to be substantially crosslinked. Upon hydration, the film formed a clear hydrogel with a water content of 72% by weight. The hydrogel was dimensionally stable under heat sterilization conditions and maintained both shape and size after two heat sterilization cycles.

In a third example, the polymer is mixed with about 6% by weight peroxide and then about 2% at 175 ° C.
It was compression molded for 2 minutes to obtain a transparent, yellowish film. The film was not soluble in organic solvents and was shown to be substantially crosslinked. Upon hydration, the film formed a clear hydrogel with a water content of about 71% by weight. The dimensions were stable under heat sterilization conditions and both shape and size were maintained after 3 heat sterilization cycles.

Example 18 In this example, copolymerization of DMA, FX-14, MMA, DCPMA and HMABP was carried out. The purpose of this example was to show a polymer that is thermally processable and photocrosslinkable. DMA (54.15% by weight), FX, according to the general polymerization procedure of the previous example (except that the reaction flask was wrapped in aluminum foil to prevent light from prematurely reacting with the HMABP photoinitiator). -14 (13.34 wt%
), MMA (11.7 wt%) and DCPMA (9.87 wt%) and HMAB
It was copolymerized with 6.68% by weight of P (3-hydroxy-1-methacryloxybenzophenone). A polymer with a T _{g of} 72 ° C. was obtained. The obtained polymer was compression-molded at 140 ° C. for about 20 minutes to obtain a transparent and yellowish film. The film dissolved in organic solvent and was shown to be uncrosslinked.

Upon hydration, the film formed a yellowish clear hydrogel with a water content of 56% by weight.

A portion of the dried film was exposed to UV radiation to activate the HMABP photoinitiator and “cure” the polymer. The film was exposed under a short-wave light source, a Black-ray Lamp Model XX-15 with a GE-F1518 BLB black light. The film was placed about 5.5 cm away from the light and exposed for about 6 hours. After this cure, the film became insoluble in organic solvents, indicating that the film was substantially crosslinked. Upon hydration, the UV cured film formed a clear hydrogel with a water content of 51% by weight. The hydrogel was dimensionally stable under heat sterilization conditions.

Example 19 In this example, copolymerization of DMA, FX-13, BEA and MPMDES (methylpropyldiethoxysilylmethacrylate) was carried out. The purpose of this example was to show a thermoprocessable, curable moisture polymer. DMA (55 wt%), FX-13 (20 wt%) according to the general polymerization procedure of the previous example.
, BEA (20 wt%) and MPMDES (5 wt%) were copolymerized with Vazo52 initiator (0.54 wt%). The obtained polymer was compression molded at 100 ° C. for about 12 minutes to obtain a transparent film. The film dissolved in organic solvent and was shown to be uncrosslinked.

A portion of the dried film was hydrated and then dehydrated. The dehydrated film was insoluble in organic solvents, indicating that the film was substantially crosslinked. Upon hydration, the moisture cured film formed a clear hydrogel with a water content of 74% by weight. The hydrogel was not dimensionally stable and became opaque under heat sterilization conditions. Alternatively, the polymer could be compression molded at 160 ° C. for about 20 minutes to obtain a transparent film. The film was insoluble in organic solvents, indicating that the film was substantially crosslinked. Upon hydration, the thermoset film formed a clear hydrogel with a water content of 70% by weight. The hydrogel was dimensionally stable under heat sterilization conditions.

In another method of practicing the invention, thermoworkable copolymer materials containing latent crosslinking groups can be synthesized so that crosslinking can be reversed after the process is complete.
It is a monomer such as N, N'-cystamine-bis-acrylamide (CB
This can be achieved by copolymerizing A) with the above-mentioned compound. H. Lee and T. Park, Polymer
See the example in Journal, vol 30., No. 12, pp. 976-980. Copolymerization of CBA with a monomer such as DMA should result in a crosslinked hydrogel forming a polymer. The disulfide bonds in the crosslinks can be subjected to chemical reduction to form thiol groups, resulting in loss of chemical crosslinks. Oxidation of thiols results in the re-formation of disulfide groups, resulting in the formation of chemical crosslinks. Examples of reducing agents include, but are not limited to, dithiothreitol, and examples of oxidizing agents include, but are not limited to, cystamine and molecular oxygen (O ₂ ). Thus, copolymers of this type containing pendant thiol side groups can be melt processed and then crosslinked to disulfide bonds by oxidation.
It is also possible to use disulfides containing dimethacrylate or diacrylate monomers to achieve a similar effect.

In yet another method of practicing the present invention, thermoworkable copolymer materials can be synthesized such that latent cross-linking occurs as a result of thermal decomposition of peroxy or azo species contained in the side chains of the copolymer. These peroxy or azo species decompose at high temperatures to form radicals. This elevated temperature is preferably above the temperature of the polymerization reaction.
The radicals formed in the decomposition induce a crosslinking reaction in the polymer by the process described above.

From the foregoing examples and discussion above, the copolymers made in accordance with the present invention,
Alternatively, it will be apparent to those skilled in the art that what is suitable for thermal processing into the ophthalmic lens of the present invention takes the form of various embodiments. In addition, this teaching allows one of ordinary skill in the art to practice the invention with a variety of monomers, including those not used in the previous examples.

To further elaborate the present invention, further embodiments constructed from the foregoing disclosure are provided. Among the considerations, this section describes a branched chain containing a polymerized hydrophilic backbone (skeleton) with polymerized hydrophobic side chains (branched chains), particularly suitable for use in the manufacture of medical devices including contact lenses. It relates to non-crosslinked hydrogels containing copolymers (also called graft copolymers or comb copolymers). Alternatively, the backbone may be hydrophobic and the side chains hydrophilic.
The copolymer is uncrosslinked, that is, has no chemically covalently bonded crosslinks. However, the copolymer achieves mechanical stability as a hydrogel due to pseudo-crosslinking (ie, physical crosslinking, eg, due to internal hydrophobic association of hydrophobic branches across different polymer molecules), which is described in detail in the previous section in the discussion above. Have been described.

The purpose of designing branched copolymers with both hydrophilic and hydrophobic segments is to make physically crosslinked hydrogels that have both high water content and significant physical strength. In general, the presence of a hydrophilic backbone in the copolymer strongly enhances moisture adsorption, resulting in a bulk material with hydrogel characteristics. On the other hand, when the material is hydrated, the hydrophobic branched chains aggregate with each other to form a separate phase, which significantly improves the physical properties of this hydrogel. The described branched copolymers, the details of which will be discussed later, can usually be synthesized by several different methods, purified in the following process and dried. The dry copolymer may be formed into a desired shape, such as a film, at a preferred temperature and then hydrated to give a hydrogel.

Although hydrogel films made from branched chain copolymers having the above structure do not contain chemical crosslinks, these hydrogels still exhibit significant mechanical strength in handling and dimensional stability in heat sterilization. The unique physical properties of these hydrogel films are primarily due to the presence of physical crosslinks associated with hydrophobic side chains. Copolymers of this type are made without thermoreactive functional groups that build up chemical cross-links, so the materials can be molded from a wide range of processing temperatures and times.

Polymerized branched copolymers useful in the method of the invention may encompass a wide range of sizes and compositions. The copolymer is preferably from about 10,000 g / mol to about 1,000.
It has a weight average molecular weight in the range of 1,000 g / mol. More preferably, the molecular weight ranges from about 50,000 g / mol to about 500,000 g / mol. Each side chain of the branched chain copolymer preferably has a weight average molecular weight of about 300 g / mol-100,000 g / mol. The polymerized side chains are covalently attached to the backbone. Macromer units having side chains preferably range from about 0 to about 95% by weight, based on the total branched copolymer. More preferably, macromer units preferably range from about 5 to about 60% by weight, based on the total copolymer. As used herein, macromers are macromolecules having active groups incorporated into the polymer backbone, such as, but not limited to, vinyl groups, and pendant groups consisting of long polymerized repeating chains or peptidomimetics. Is believed to be.

In general, branched copolymers containing a hydrophilic backbone with hydrophobic side chains can be prepared by the three possible routes shown below. However, these methods are not the only way to build copolymers with branched chains.

(A) Copolymerization of Monomers with Macromers Branched chain copolymers can be synthesized directly from a mixture of monomers and macromers and an initiator. Suitable monomers for use herein can be hydrophilic or a mixture of hydrophilic and hydrophobic. Suitable macromers for use herein can be hydrophobic, or a mixture of hydrophobic and hydrophilic. In this embodiment, the selected macromers are polydimethylsiloxane monomethacrylate (hydrophobic macromers) and poly (ethylene glycol) methylethyl acrylate macromers (hydrophilic macromers), which are commercially available catalog suppliers such as
This is because it is conveniently available from Gelest or Aldrich. The synthesis of other hydrophobic and hydrophilic macromers with the desired composition is described in published literature, eg K. Ito, N. U.
The method described in Sami, and Y. Yamashita, Macromolecules, 13, 216 (1980) can be used. For example, one of the proposed reaction schemes is shown below, which is one of the possible methods for preparing hydrophobic or hydrophilic macromers.

[0221]

[Chemical 13]

The monomers used in this synthesis can be any kind of hydrophilic or hydrophobic monomers, and also blends of both. It is not particularly limited to 2- (N-ethylperfluorooctanesulfonamido) ethyl acrylate (FX-13) used in this example.

Example 20 In this example, copolymerization of dimethylacrylamide, FX-13 and polydimethylsiloxane monomethacrylate (M _w = 5,000) was carried out. The purpose of this example is to describe a branched chain copolymer made by chemically initiating a radical polymerization reaction in one step using vinyl monomers having long hydrophobic side chains.

To a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet, toluene (180 mL), dimethylacrylamide (DMA) (64
． 7% by weight), 2- (N-ethylperfluorooctanesulfonamido) ethyl acrylate (FX-13) (20% by weight) and monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 5,000 (15 Wt%) as well as Vazo 64 (0.3 wt%). The total mass of monomers was 30 g. The solution was purged with nitrogen for 10 minutes, then thermally initiated at 60 ° C. and polymerized for 20 hours. Instead, the monomer was added to the Rayonet-600 reaction chamber (4 watt x 4, λ = 365 m
It is also possible to photoinitiate in m) and polymerize at room temperature for about 20 hours. After collecting the branched chain copolymer and drying, the material was compression molded into a film at 160 ° C. and then hydrated to give a hydrogel. The expected copolymer structure is shown below and the characterization results for both the dry copolymer and the hydrogel are summarized in Table 7 below.

[0225]

[Chemical 14]

Examples 21-24 below describe the effect of hydrophobic side chains on the properties of dry copolymers and hydrogels. The structures of these copolymers are similar to those described above.

Example 21 In this example, copolymerization of dimethylacrylamide, FX-13 and polydimethylsiloxane monomethacrylate (M _w = 1,000) was carried out.

To a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet, toluene (200 mL), dimethylacrylamide (DMA) (54
． 7% by weight), 2- (N-ethylperfluorooctanesulfonamido) ethyl acrylate (FX-13) (20% by weight) and monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 1,000 (25 Wt%) as well as Vazo 64 (0.3 wt%). The total mass of the monomers was 50 g. The solution was purged with nitrogen for 10 minutes and then photoinitiated in a Rayonet-600 reaction chamber (4 watt x 4, λ = 365 mm) and polymerized for about 20 hours at room temperature. (Alternatively, it is possible to heat-initiate the monomer at 60 ° C. and polymerize for 20 hours.) After collecting the branched chain copolymer and drying, the material is compression molded into a film at 160 ° C.,
It was then hydrated to give a hydrogel. The results of the characterization of both the dry copolymer and the hydrogel are summarized in Table 7 below.

Example 22 In this example, copolymerization of dimethylacrylamide, FX-13 and polydimethylsiloxane monomethacrylate (M _w = 10,000) was performed.

Branched chain copolymers were prepared according to the procedure of Example 20 except that the hydrophobic macromer used had large numbers of repeating units. Toluene (180 mL) in a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet,
Dimethylacrylamide (DMA) (64.7% by weight), 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate (FX-13) (20% by weight) and monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 10,000 (15 wt%) as well as Vazo 64 (0.3 wt%) were charged. The total mass of monomers was 30 g. The solution was purged with nitrogen for 10 minutes and then the monomers were thermally initiated at 60 ° C to polymerize for about 20 hours. The branched chain copolymer was collected and dried. Molecular weight (based on GPC): M _w = 160,000. Differential Scanning Calorimetry: The copolymer showed a glass transition temperature of 110 ° C. After compression molding into a film at 160 ° C, the material was hydrated to give a hydrogel. The dried film was translucent and showed a rough surface. The water content of the hydrogel was 74%.

Example 23 In this example, the copolymerization of dimethylacrylamide, FX-13 and polydimethylsiloxane monomethacrylate (M _w = 10,000) was carried out.

The branched chain copolymer was prepared according to the procedure of Example 22 except that a larger proportion of the same hydrophobic macromer was used. To a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, a reflux condenser and a nitrogen inlet, toluene (180 mL), dimethylacrylamide (DMA) (49.7% by weight), 2- (N-ethylperfluorooctanesulfonamide) ) Ethyl acrylate (FX-13) (20 wt%) and monoacryloxypropyl-terminated polydimethylsiloxane, _Mw = 10,000 (30 wt%) and Vazo64 (0.3 wt%) were charged. . The total mass of monomers was 30 g. Purge the solution with nitrogen for 10 minutes,
The monomers were then thermally initiated at 60 ° C and polymerized for about 20 hours. After the branched copolymer was collected and dried, the material was compression molded into a film at 160 ° C and then hydrated to give a hydrogel. The branched chain copolymer was collected and dried. Molecular weight (GPC
Based): M _w = 166,000. Differential Scanning Calorimetry: The copolymer showed a glass transition temperature of 104 ° C. After compression molding into a film at 160 ° C, the material was hydrated to give a hydrogel. The dried film was slightly hazy and showed a slightly rough surface. The water content of the hydrogel was 68%.

Example 24 In this example, copolymerization of dimethylacrylamide, FX-13 and polydimethylsiloxane monomethacrylate (M _w = 5,000) was carried out.

[0234]   The branched chain copolymer was used except that a larger proportion of hydrophobic macromer was used.
Prepared according to the procedure of Example 20. Mechanical stirrer, reflux condenser and nitrogen inlet
Toluene (180 mL), dimethy
Luacrylamide (DMA) (49.7% by weight), 2- (N-ethylperfluor)
Rooctanesulfonamide) ethyl acrylate (FX-13) (20% by weight)
And monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 5,000 (30% by weight) and Vazo64 (0.3% by weight) were added.
. The total mass of monomers was 30 g. The solution was purged with nitrogen for 10 minutes, then 6
Polymerization was initiated by heating at 0 ° C for about 20 hours. Collect the branched chain copolymer and dry
After that, the material was compression molded into a film at 160 ° C. and then hydrated to obtain a hydrogel.
. The results of the characterization of both dry copolymer and hydrogel are summarized in Table 7 below.
I have

Example 25 In this example, copolymerization of dimethylacrylamide (DMA), FX-13, polydimethylsiloxane monomethacrylate and polyethylene glycol methyl ether acrylate was carried out. The purpose of this example is to describe a branched chain copolymer with long hydrophobic and hydrophilic side chains. Hydrophilic side chains can be useful for improving the surface wettability of contact lenses made from this material.

A branched chain copolymer was prepared according to the procedure of Example 20 except that the formulation contained both hydrophilic and hydrophobic macromers in the polymerization flask. Toluene (into a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet)
180 mL), dimethyl acrylamide (DMA) (14.16 g, 142.89)
mmol), 2- (N-ethylperfluorooctanesulfonamido) ethyl acrylate (FX-13) (6.00 g, 10.24 mmol), monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 5,000. (7.50 g
, 1.50 mmol) and poly (ethylene glycol) methyl ethyl acrylate, M _w = 454 (2.25 g, 4.96 mmol) and Vazo 64 (0.3 wt%). The solution was purged with nitrogen for 10 minutes and then photoinitiated in a Rayonet-600 reaction chamber (4 watt x 4, λ = 365 mm) and polymerized for about 20 hours at room temperature. (Alternatively, it is possible to heat-initiate the monomer at 60 ° C. and polymerize for 20 hours.) After collecting and drying the branched chain copolymer, the material is compression molded into a film at 160 ° C. and then hydrated. To obtain a hydrogel. The expected polymer structure is shown below and the results of the characterization of both dry copolymer and hydrogel are summarized in Table 7 below.

Examples 26-28 below illustrate the effect of both hydrophobic and hydrophilic side chains on the properties of both dry copolymers and hydrogels. The structures of these copolymers are similar to those described above.

Example 26 In this example, copolymerization of dimethylacrylamide (DMA), FX-13, polydimethylsiloxane monomethacrylate and polyethylene glycol methyl ether acrylate was carried out.

Example 25 except that the branched chain copolymer was used at a high proportion of hydrophilic monomer.
Was prepared according to the procedure of. To a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet, toluene (180 mL), dimethylacrylamide (DMA) (39.7% by weight), 2- (N-ethylperfluorooctanesulfonamide) ) Ethyl acrylate (FX-13) (20% by weight), monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 5,000
(25.0 wt%) and poly (ethylene glycol) methyl ether acrylate, M _w = 454 (15.0 wt%) and Vazo 64 (0.3 wt%) were charged. The total mass of monomers was 30 g. The solution was purged with nitrogen for 10 minutes and then photoinitiated in a Rayonet-600 reaction chamber (4 watt x 4, λ = 365 mm) and polymerized for about 20 hours at room temperature. (Alternatively, heat the monomer at 60 ° C. to 2
It is also possible to polymerize for 0 hours. ) After collecting the branched chain copolymer and drying,
The material was compression molded into a film at 160 ° C and then hydrated to give a hydrogel. The results of the characterization of both the dry copolymer and the hydrogel are summarized in Table 7 below.

[0240]

[Chemical 15]

Example 27 In this example, copolymerization of dimethylacrylamide (DMA), FX-13, polydimethylsiloxane monomethacrylate and polyethylene glycol methyl ether acrylate was carried out.

To a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet, toluene (180 mL), dimethylacrylamide (DMA) (54
． 7% by weight), 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate (FX-13) (20.0% by weight), monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 5,000. (15.0% by weight)
And poly (ethylene glycol) methyl ether acrylate, M _w = 110
0 (10 wt%) and Vazo 64 (0.3 wt%) were added. The total mass of monomers was 30 g. The solution was purged with nitrogen for 10 minutes and heat initiated at 60 ° C to polymerize for 20 hours. After collecting the branched chain copolymer and drying, the material was compression molded into a film at 160 ° C. and then hydrated to give a hydrogel. The results of the characterization of both the dry copolymer and the hydrogel are summarized in Table 7 below.

Example 28 In this example, copolymerization of dimethylacrylamide (DMA), FX-13, polydimethylsiloxane monomethacrylate and polyethylene glycol methyl ether acrylate was performed.

A branched copolymer was prepared according to the procedure of Example 27, except that a large amount of hydrophobic macromer was used. 5 with mechanical stirrer, reflux condenser and nitrogen inlet
Toluene (180 mL), dimethylacrylamide (DMA) (39.7% by weight), 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate (FX-13) (20.0% by weight) in a 00 mL four-necked cylinder flask. ), Monoacryloxypropyl-terminated polydimethylsiloxane, M _w = 5,000
0 (30.0 wt%) and poly (ethylene glycol) methyl ether acrylate, M _w = 1100 (10 wt%) and Vazo 64 (0.3 wt%) were charged. The total mass of monomers was 30 g. The solution was purged with nitrogen for 10 minutes, then thermally initiated at 60 ° C. and polymerized for 20 hours. After collecting the branched chain copolymer and drying, the material was compression molded into a film at 160 ° C. and then hydrated to give a hydrogel. The expected polymer structure is shown below and the results of the characterization of both dry copolymer and hydrogel are summarized in Table 7 below.

Example 29 In this example, copolymerization of dimethylacrylamide (DMA), FX-13, polydimethylsiloxane monomethacrylate and polyethylene glycol methyl ether acrylate was performed.

The branched chain copolymer was prepared according to the procedure of Example 27 except that a different initiator (Vazo52) was used. To a 500 mL four-necked cylinder flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet, toluene (150 mL), dimethylacrylamide (DMA) (54.5% by weight), 2- (N-ethylperfluorooctanesulfonamide) ) Ethyl acrylate (FX-13) (20.0% by weight)
, Monoacryloxypropyl-terminated polydimethylsiloxane, M _w =
5,000 (15.0 wt%) and poly (ethylene glycol) methyl ether acrylate, M _w = 1100 (10 wt%) and Vazo 52 (0.3 wt%) were charged. The total mass of monomers was 30 g. The solution was purged with nitrogen for 20 minutes and then thermally initiated at 45 ° C to polymerize for 20 hours. The branched chain copolymer was collected and dried. The results of the characterization of both the dry copolymer and the hydrogel are summarized in Table 7 below.

(B) Grafting Hydrophobic Side Chains onto Hydrophilic Main Chains In this graft polymerization technique, branched chain copolymers were prepared by two successive polymerization reactions. In the first step, the polymerizing backbone is prepared in a small amount, preferably about 0.5, using either hydrophilic or hydrophobic monomers, or a mixture of hydrophilic and hydrophobic monomers or a macromer, or a mixture of both. % To about 30% functional monomer, and can be synthesized by well-known polymerization techniques including chain growth, step growth, Ziegler-Natta and group transfer polymerization. Functional monomers as defined herein include all types of active functional groups that can be used to graft side chains.

Polymerization side chains grafted from active sites can be polymerized from hydrophobic or hydrophilic monomers, or hydrophobic and hydrophilic monomers or macromers or a mixture of both monomers and macromers to the desired chain length. Chain length can be controlled by the ratio of the concentration between the polymerizable units used to make the side chains to the active site of the backbone. One type of active site used in the present invention is represented by an organic halide moiety, which is Atom Transfer Radical Polymerization (ATRP).
It can be grafted with monomers in the art. This technology is Matyjaszewski
Et al., U.S. Pat. No. 5,763,548, incorporated herein by reference.

In the examples below, backbone copolymers were prepared by copolymerizing a monomer mixture containing 1 to 5 wt% of an organic halide-containing monomer, based on total monomer content. The halogen atom of this monomer need not be chlorine as used in these examples, but can be bromine, iodine, or fluorine. The final graft copolymer is composed of about 50-75% by weight hydrophilic backbone and about 25-50% by weight hydrophobic side chains. The ratio of hydrophilic backbone to hydrophobic side chains can be as wide as possible. Alternatively, the backbone may be hydrophobic and the side chains hydrophilic. The resulting polymer hydrogel is characterized by a hydrophilic continuous phase. The degree of grafting can be measured by the FT-IR peak ratio of carbonyl groups of ester and amide groups. The ratio of ester to amide increases with the degree of grafting.

Example 30 In this example, copolymerization of dimethylacrylamide, FX-13 and vinylbenzyl chloride was followed by grafting of poly (methylmethacrylate). The purpose of this example is to describe a multi-step polymerization technique that builds a branched copolymer that is suitable for thermal processing into ophthalmic lenses.

To a 500 mL three-necked round bottom flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet, toluene (180 mL), 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate (FX-13, 6 (0.000 g, 10.24 mmol),
Dimethyl acrylamide (DMA, 23.61 g, 238.24 mmol), vinylbenzyl chloride (0.30 g, 1.97 mmol) and AIBN (azobisisobutyronitrile, 0.09 g, 0.55 mmol) were charged. After purging with nitrogen for 10 minutes, the mixture was copolymerized with a slow stream of nitrogen at 60 ° C. for about 20 hours, then about 10 minutes.
Further heat at 0 ° C. for about 1 hour. After cooling the solution to room temperature, toluene (60 mL)
, Methyl methacrylate (10.00 g, 100 mmol), CuCl (0.194
8g, 1.97mmol) and 2,2'-dipyridine (0.9218g, 5.90).
was added to a round bottom flask and then heated at 120 ° C. for about 6 hours. After cooling to room temperature, the catalyst was removed by filtration, then the filtrate was precipitated in hexane. The isolated solid was washed several times with hot water and subsequently dried in a vacuum oven. The dry material was compression molded into a film at 160 ° C and then hydrated to give a hydrogel. The expected polymer structure is shown below and the results of the characterization of both dry copolymer and hydrogel are summarized in Table 7 below.

[0252]

[Table 7]

[Chemical 16]

Example 31 In this example, the copolymerization of dimethylacrylamide and vinylbenzyl chloride was performed. The obtained polymer was used for the subsequent graft polymerization.

Dimethyl acrylamide (DMA, 95.0 g), vinylbenzyl chloride (VBC, 5.0 g), VAZO 52 (0..0.) In a 500 mL three-necked flask equipped with a condenser, mechanical stirring unit, balloon and gas inlet. 51 g) and toluene (500 mL) were added. The flask was filled with nitrogen until the balloon (9 inch volume) was inflated. The balloon was evacuated and the reaction vessel evacuated until the contents of the flask began to bubble. At this point the vacuum was discontinued and the flask was bleed with nitrogen until the 9 inch balloon was inflated. The reaction mixture was degassed and then filled with nitrogen about 4 times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture was stirred under nitrogen at about 45 ° C. for about 24 hours. The reaction mixture was poured into about 500 mL of stirring hexane and the copolymer was isolated. After soaking for about 30 minutes, the solvent was decanted from the precipitated copolymer. The copolymer was washed with about 300 mL of fresh hexane and then vacuum dried at about 60 ° C. for about 1 day. Samples were analyzed by UV-VIS, FT-IR and DSC. UV-VIS (sample in chloroform): peak concentrated at 244 nm. FT-IR (film cast from chloroform to NaCl, selected peaks): 2928, 2863, 16
43, 1496, 1463, 1399, 1355, 1259, 1139, 1096, 1058 cm ^-1 . Differential scanning calorimetry:
The polymer exhibited a glass transition temperature of 100 ° C.

Example 32 In this example, the copolymerization of dimethylacrylamide, n-octadecyl acrylate and vinylbenzyl chloride was performed. The obtained polymer was used for the subsequent graft polymerization.

In a glass kettle reactor equipped with an overhead stirrer (Teflon blade), balloon, condenser and gas inlet, dimethylacrylamide (DMA, 79.
32 g, 79.20% by weight), vinylbenzyl chloride (VBC, 5.14 g,
5.13% by weight), n-octadecyl acrylate (ODA, 14.85 g, 1
4.82 wt%), VAZO64 (0.85 g, 0.85 wt%) and butyl acetate (1300 mL) were charged. The flask was immersed in a water bath and filled with nitrogen until the balloon (9 inch volume) was inflated. The reaction vessel was depressurized until the contents of the flask began to bubble. At this point the vacuum was discontinued and the flask was bleed with nitrogen until the 9 inch balloon was inflated. The reaction mixture is degassed and then
Filled with nitrogen about 6 times. The reaction mixture was left under nitrogen and the overhead stirrer was started. The reaction mixture was stirred under nitrogen at about 60 ° C. for about 20 hours. At this point, about 0.5 mL of sample was removed from the reaction flask and mixed with about 20 mL of hexane. The resulting precipitate was filtered and washed with about 20 mL of hexane. A few milligrams of the isolated product were dissolved in chloroform and analyzed by UV-VIS analysis. The sample showed a peak centered around 244 nm. The bath temperature was then raised to about 70 ° C. for about 1 hour. The polymer solution was stored in a sealed container and used for the subsequent preparation of the graft copolymer by atom transfer radical polymerization (ATRP).

The above-precipitated sample was dried under reduced pressure at about 60 ° C. and then analyzed by FT-IR and DSC. FT-IR (film cast from chloroform to NaCl, selected peaks): 2924.3, 2854.0, 1728, 1643, 1494, 1463, 1398.
, 1354, 1259, 1139, 1096, 1059 cm ^-1 . Differential Scanning Calorimetry: The polymer showed a glass transition temperature of 95 ° C. Upon compression molding at 130 ° C. for 5 minutes under a pressure of 8 metric tons, the copolymer formed a clear, brittle film. The film formed a clear hydrogel, which could not support its own weight.

Example 33 In this example, graft copolymerization of poly (n-butyl acrylate) with the polymer of Example 32 was performed. The purpose of this example is to describe the second step of the polymerization technique to build a branched copolymer suitable for thermal processing into ophthalmic lenses.

A three necked flask equipped with a condenser, mechanical stirrer unit and gas inlet was charged with about 20 g of poly (DMA / VBC / ODA) in about 245 mL of butyl acetate (Example 32). In a flask, N, N, N ', N', N "-pentamethyldiethylenetriamine (PMDETA, 3.53 g), copper (I) chloride (0.67 g)
And n-butyl acrylate (BA, 20.3 g) were added. Nitrogen was bubbled through the reaction mixture for 10 minutes. Then the nitrogen flow is reduced and the mixture is heated to 10 for 22 minutes.
Heated to 0 ° C. A balloon was then attached to the reaction flask and inflated with nitrogen. The reaction mixture was then heated at 100 ° C. for 24 hours. The reaction mixture was diluted with 100 mL THF and 200 mL water. Water was added to precipitate the copolymer. The aqueous phase was removed and 700 mL of fresh water was added to the copolymer. The sample was washed several times with 700 mL of water each time and then dissolved in 250 mL of acetone. The acetone solution was stirred with 50 g of neutral aluminum oxide. The aluminum oxide was removed by filtration, then the resulting acetone solution was added to 700 mL of stirring hexane. The obtained precipitate was separated, washed twice with 100 mL of hexane, and dried under reduced pressure at 60 ° C. for about 24 hours. Polymer F
It was analyzed by T-IR and DSC. FT-IR (film cast from chloroform to NaCl, selected peaks): 2926, 2856, 1732, 1643, 1497,
1465, 1398, 1259, 1140, 1096, 1065cm ^-1 . Differential scanning calorimetry: glass transition temperature 7
4 ° C was detected.

The polymer was compression molded at 150 ° C. for 30 minutes under a load of 8 metric tons to give a transparent, yellowish, flexible film. The material retained thermoplasticity as indicated by being able to be reshaped. The film formed a hydrogel with a water content of 73%. The hydrogel has a breaking stress of 0.2 N / mm ² and an elongation at break of 186.
%Met. Discs (13 mm) cut from hydrogel sheets did not retain their shape and dimensions when heat sterilized in an autoclave at 120 ° C for 45 minutes. We
Discs cut from hydrogels boiled in sley Jessen lens package solution and heat treated (100 ° C. for 5 minutes) maintained their shape and dimensions when autoclaved.

Example 34 In this example, graft copolymerization of poly (methyl methacrylate) and the polymer of Example 32 was performed.

Butyl acetate (Example 32) Poly (DMA / VBC / OD) in about 245 mL.
A) About 20 g, N, N, N ', N', N "-pentamethyldiethylenetriamine (PMDETA) 3.51 g, copper (I) chloride 0.68 g and methyl methacrylate (MMA) 20.7 g are used. Polymerized according to the procedure of Example 33. After purging with nitrogen, the mixture was heated for 22 minutes to 105 ° C. The reaction mixture was then heated for 20 hours at 105 ° C. The reaction mixture was stirred. The co-precipitate was poured into 700 mL of hexane and the precipitate was filtered, washed 3 times with 500 mL of water and immersed in 700 mL of water for 48 hours.
And dried under reduced pressure for about 9 hours. The polymer was analyzed by FT-IR and DSC. FT
-IR (film cast from chloroform to NaCl, selected peaks): 2925, 2857, 1730, 1643, 1486, 1451, 1398, 1354, 1265, 1191, 1147,
1097, 1059 cm ^-1 . Differential scanning calorimetry: A glass transition temperature of 69 ° C. was detected.

The polymer was compression molded at 130 ° C. for 7 minutes under a load of 8 metric tons to give a clear, brownish, brittle film. The material retained thermoplasticity as indicated by being able to be reshaped. The film formed a hydrogel with a water content of 57%.
The hydrogel had a breaking stress of 0.4 N / mm ² and an elongation at break of 60%.
Discs (13 mm) cut from hydrogel sheets did not retain their shape and dimensions when boiled and heat treated at 100 ° C. for 10 minutes in Wesley Jessen lens package solution. However, after further heat treatment for 10 minutes or 30 minutes, no further loss of shape occurred. Discs cut from hydrogels boiled and heat-treated (100 ° C. for 5 minutes) in Wesley Jessen lens packaging solution did not retain their shape and dimensions when sterilized in an autoclave at 120 ° C. for 45 minutes.

Example 35 In this example, graft copolymerization of poly (n-octadecyl acrylate) and the polymer of Example 32 was performed.

Butyl acetate (Example 32) Poly (DMA / VBC / OD) in about 245 mL.
A) About 20 g, N, N, N ′, N ′, N ″ -pentamethyldiethylenetriamine (PMDETA) 3.51 g, copper (I) chloride 0.67 g and n-octadecyl acrylate (ODA) 20.0 g are used. Polymerization was carried out according to the procedure of Example 33, except that after purging with nitrogen, the mixture was heated to 100 ° C. for 22 minutes, the flask was fitted with a balloon and filled with nitrogen. Was heated for 48 hours at 100 ° C. The reaction mixture was poured into 700 mL of stirring hexane to precipitate the copolymer.The resulting precipitate was filtered and washed 5 times with 300 mL of water. The polymer was dried under reduced pressure for 24 hours in THF 60.
It was dissolved in 0 mL and 150 mL of water was added. The mixture is filtered and neutral aluminum oxide 2
It was passed between 00 g and then concentrated on a rotary evaporator. The polymer was filtered from residual water and washed twice with 250 mL of water. The polymer was dried under vacuum at 75 ° C for 9 hours. The polymer was analyzed by FT-IR and DSC. FT-IR (film cast from chloroform to NaCl, selected peaks): 2924
, 2853, 1729, 1642, 1496, 1465, 1398, 1354, 1259, 1139, 1100, 1060 cm ^-1 .
Differential scanning calorimetry: A glass transition temperature of 74 ° C. was detected.

The polymer was compression molded for 30 minutes at 150 ° C. under a load of 8 metric tons to give a transparent, brownish, flexible film. The material retained thermoplasticity as indicated by being able to be reshaped. The film formed a hydrogel with a water content of 65%. The hydrogel has a breaking stress of 0.3 N / mm ² and an elongation at break of 106.
%Met. Discs (13 mm) cut from hydrogel sheets did not retain their shape and dimensions when heat sterilized in an autoclave at 120 ° C for 45 minutes. We
Discs cut from hydrogels boiled in sley Jessen lens package solution and heat treated (100 ° C. for 5 minutes) maintained their shape and dimensions when autoclaved.

The graft copolymers prepared according to the invention can be modified from the examples mentioned above. For example, the molecular weight of the precursor polymers as described in Examples 31 and 32 can be varied by changing the reaction conditions during the polymerization process. These changes further include, but are not limited to, changing the reaction temperature, changing the concentration of the initiator, and adding a chain transfer agent such as, but not limited to, 1-decanethiol. Another property that depends on reaction conditions and monomer feed is the fine structure of the graft chains. The graft chains can be polymerized such that the chains have a diblock, triblock or multiblock structure or a random or alternating structure. Any of the monomers presented herein are useful as components of the graft chain polymerization mixture.

Further modifications of the graft copolymer are within the scope of the invention. The halocarbon end groups of the grafted chain, when the polymer is exposed to suitable heat, light or chemical reagents,
It can function as a latent crosslinking agent for the polymer. Nucleophilic substitution of halocarbons is well known. Possible nucleophilic substitution reagents include polyfunctional primary or secondary amines (eg 1,4-diaminobutane and various isomers thereof), diols, triols and polyols such as ethylene. Included, but not limited to, glycols, glycerin, poly (ethylene glycol) and poly (vinyl alcohol). Halogen groups can also be substituted with hydroxyl, alkoxide or aryl oxide. Hydroxyl groups can be obtained by treating the polymer with a water-containing solution under acidic, basic or neutral conditions. Alkoxide or aryloxide groups can be obtained by heating the polymer in the presence of alcohol, alkoxide or aryloxide. Also, photolysis of solutions containing polymers and reagents such as chloroform or 1-decanethiol can result in halogen exchange by halogen atoms.

(C) Chemical Coupling of Hydrophobic Side Chains to Hydrophilic Main Chains Branched-chain copolymers also polymerize the polymerized hydrophobic side chains after the main chain and side chains of the copolymer have been prepared by separate reactions. It can be prepared by other potential methods of attaching to the hydrophilic backbone by post chemical reactions. Described below are proposed methods that can be used to synthesize branched chain copolymers. For example, polymerized hydrophilic backbones can be prepared by copolymerizing a small amount of monomers containing primary or secondary amino groups, while polymerized hydrophobic side chains have organic halide moieties at the chain ends. AT to do
It can be prepared by RP. It is possible to obtain a branched chain copolymer in which the polymerized branched chain is bonded to the main chain through a chemical bond by mixing the main chain and the side chain before the synthesis of these copolymers and then performing a nucleophilic substitution reaction.

Blend Copolymers In another method of practicing the present invention, melt processable polymeric materials are composited (blended).
Can be developed from materials. The composite material may be composed of two or more different copolymers that are somewhat miscible. The copolymers must be sufficiently compatible to be homogeneously blended to avoid assemblages that can result in opaque or optically opaque ophthalmic lenses.

Polymers with various compositions may be prepared by separate polymerization reactions and blended with each other in different proportions. The complex can include at least two different copolymers, each containing a hydrophilic and a hydrophobic unit. Alternatively, the composite can include hydrophobic polymers or copolymers and copolymers containing hydrophilic and hydrophobic units. The purified composite can also be shaped into the desired shape as discussed in the several embodiments above. The types of composite materials that can be made include both thermoplastic (linear and branched copolymers) and thermoset (chemically crosslinked copolymers) materials. The aforementioned curing technology (heat curing, light curing,
(Including moisture cure, redox cure, etc.) are also suitable for the thermoset blend copolymers described herein. This method of the invention can more easily provide melt-fabricable polymers capable of forming hydrogels.

The foregoing preferred embodiments and examples illustrate the scope and spirit of the invention. These embodiments do not limit the invention, but it will be clear to the person skilled in the art that other embodiments and examples are within the intended scope of the invention. Therefore, the present invention should be limited only by the claims.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) C08F 290/14 C08F 290/14 C08J 3/075 CEY C08J 3/075 CEY G02B 1/04 G02B 1/04 G02C 7/04 G02C 7/04 // C08L 33:00 C08L 33:00 (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT , LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM) , KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, T ), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CR, CU, CZ, DE, DK, DM, DZ, EE , ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR , TT, TZ, UA, UG, UZ, VN, YU, ZA, ZW (72) Inventor Ferran, John Sea United States, Illinois 60031, Gurney, Dorchester Avenue 4137 (72) Inventor Chan, Frank Frank WK Iri, United States A 60516, Downers Grove, Penner Avenue 7037 F Term (Reference) 2H006 BA01 BB01 BB06 4F070 AA32 AA35 CB02 GA04 GA06 GB09 GC03 4F213 AA21 AH74 WA02 WA04 WA08 WA53 WA90 WB01 4J027 AF05 BA07 BA14 4Q10 AL03QQ AB02QQQQQQQQQQQQQQQU BA59R CA04 CA05 CA31 DA23 DA47 DA51 HA53 HA61 HA62 HC08 HC10 HC25 HC43 HC51 HC55 HE22 HG23

Claims (156)

[Claims] 1. A) about 20-90% by weight of the total monomers of at least one hydrophilic monomer, and b) about 5-80% by weight of the total monomers of at least one copolymerizable hydrophobic monomer. , A polymer prepared by polymerizing a monomer comprising, wherein said polymer is melt processable at a temperature of about 50-300 ° C. and contains about 35 to about 90% by weight water based on the total hydrated polymer. A polymer, which is capable of forming a hydrogel having an index and is optically transparent. 2. The polymer of claim 1, wherein the polymer is melt processable at temperatures of about 80-250 ° C. 3. The polymer of claim 1, wherein the polymer is melt processable at temperatures of about 115-200 ° C. 4. The hydrogel has an oxygen permeability of about 8 to about 50 barrers,
The polymer of claim 1 having a tear strength of greater than about 1 g / mm and a tensile modulus of about 20 to about 140 g / mm ² . 5. The polymer according to claim 1, wherein the hydrophilic monomer and the hydrophobic monomer are vinyl monomers. 6. The hydrophilic monomer is N, N-dimethylacrylamide,
2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 2
-Ethoxyethyl methacrylate, N-vinylpyrrolidone, glycidyl methacrylate, 2,3-dihydroxypropyl methacrylate, 1,3-dihydroxy acrylate, 2,3-dihydroxypropyl acrylate, 3-hydroxypropyl methacrylate, 3-hydroxypropyl acrylate, 2- Hydroxypropyl acrylate, polyhydroxysuryl alkyl acrylate, acrylamide, acrylic acid, methacrylic acid, 4-hydroxybutyl methacrylate,
4-hydroxybutyl acrylate, N- (2-hydroxypropyl) methacrylamide, N-methylmethacrylamide, poly (ethylene glycol) monomethacrylate, poly (ethylene glycol) monomethyl ether monomethacryl,
From N-vinyl-N-methylacetamide, vinylmethylsulfone, N-acryloylmorpholine, N-methacryloylmorpholine, N-methacryloylpiperidine, N-alkylacryloylamide, acid functional monomers, salts thereof, and combinations thereof. The polymer of claim 1 selected from the group consisting of: 7. The polymer of claim 1, wherein the hydrophilic monomer is selected from the group consisting of acrylamide, methacrylamide, acrylate, methacrylate monomers, and combinations thereof. 8. The hydrophobic monomer is an alkylated alkyl acrylate,
Styrene, t-butyl styrene, substituted acrylamides and methacrylamides,
A polymer according to claim 1 selected from the group consisting of as well as combinations thereof. 9. The polymer of claim 1, wherein the at least one hydrophobic monomer comprises a fluorinated monomer. 10. The fluorinated compound is 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate, 2- (N-ethylperfluorooctanesulfonamide) ethyl methacrylate, hexafluoroisopropyl acrylate, 1H, 1H, 2H, 2H-heptadecafluorodecyl acrylate,
10. The polymer of claim 9, selected from the group consisting of pentafluorostyrene, trifluoromethylstyrene, fluorostyrene, pentafluoroacrylate, pentafluoromethacrylate, and combinations thereof. 11. The polymer of claim 1, wherein the at least one hydrophobic monomer comprises a silicon-free monomer. 12. The polymer of claim 1, wherein the monomer further comprises at least one high refractive index monomer. 13. The polymer of claim 1, wherein the monomer further comprises a UV absorbing monomer. 14. The polymer of claim 1, wherein the monomer further comprises another hydrophobic monomer. 15. The polymer of claim 1, wherein the polymer is substantially free of crosslinker. 16. The polymer of claim 15, wherein the polymer further comprises long side chains having a molecular weight of 500 to 50,000 that substantially enhance the dimensional stability of the polymer when hydrated. 17. The polymer of claim 16, wherein one or more of the hydrophilic or hydrophobic monomers comprises long side chains having a molecular weight of 500-50,000. 18. A) about 20-90% by weight of the total monomers of at least one hydrophilic monomer, and b) about 5-80% by weight of the total monomers of at least one copolymerizable hydrophobic monomer. An ophthalmic lens made from a hydrogel polymer prepared by hydrating a non-hydrated polymer prepared by polymerizing a monomer comprising: 35 to about 90% by weight of water,
In the unhydrated state, the polymer is melt processable at temperatures of about 50-300 ° C. 19. The polymer of claim 18, wherein the polymer is melt processable at a temperature of about 80-250 ° C. 20. The polymer of claim 18, wherein the polymer is melt processable at temperatures of about 115-200 ° C. 21. The hydrophobic monomer comprises a fluorinated monomer.
The lens according to item 8. 22. The lens of claim 18, wherein the monomer further comprises at least one high refractive index monomer. 23. The lens of claim 18, wherein the monomer further comprises at least one UV absorbing monomer. 24. The lens of claim 18, wherein the hydrogel polymer is dimensionally stable up to a temperature of about 50 ° C. 25. The lens of claim 18, wherein the hydrogel polymer is dimensionally stable up to a temperature of about 140 ° C. 26. The lens of claim 18, wherein the hydrogel polymer is substantially free of crosslinks. 27. The lens of claim 26, wherein the hydrogel polymer further comprises long side chains having a molecular weight of 500 to 50,000 that substantially enhance the dimensional stability of the hydrogel polymer. 28. One or more of the hydrophilic or hydrophobic monomers are:
28. The polymer of claim 27, which comprises long side chains having a molecular weight of 500 to 50,000. 29. A melt-processible block copolymer having substantially no chemical cross-linking, said non-cross-linked copolymer comprising blocks which self-separate into mutually immiscible phases at the intended use temperature. In, the main component includes a block containing a hydrophilic unit, the sub-component includes a block containing a hydrophobic unit, the hydrophobic block of the sub-component is dissociated at a high temperature of higher than about 80 ℃, Up to at least about 60 ° C. when the copolymer is hydrated by providing a copolymer that can be heat processed into a service implement and the hydrophobic block of the subcomponent provides a sufficient amount of internal hydrophobic bonds. A dimensionally stable hydrogel is obtained at a temperature of
A copolymer characterized by the following. 30. The copolymer has a refractive index of about 1. upon hydration.
30. The copolymer of claim 29, which is capable of forming a hydrogel that is 4. 31. The copolymer of claim 29, wherein the copolymer has a single glass transition temperature of about 30-200 ° C. 32. The copolymer of claim 29, wherein the copolymer is capable of absorbing a sufficient amount of water to obtain a hydrated material containing at least about 35% by weight of the hydrated lens. . 33. A contact lens comprising the copolymer of claim 29. 34. Corneal transplant tissue comprising the copolymer of claim 29. 35. An intraocular lens comprising the copolymer of claim 29. 36. The hydrophilic unit is N, N-dimethylacrylamide, 2
-Hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 2-
Ethoxyethyl methacrylate, N-vinylpyrrolidone, glycidyl methacrylate, 2,3-dihydroxypropyl methacrylate, 2,3-dihydroxypropyl acrylate, 3-hydroxypropyl methacrylate, 3-hydroxypropyl acrylate, polyhydroxysurylalkyl acrylate, acrylamide, acrylic Acid, methacrylic acid, 4-hydroxybutyl methacrylate,
4-hydroxybutyl acrylate, N- (2-hydroxypropyl) methacrylamide, N-methylmethacrylamide, poly (ethylene glycol) monomethacrylate, poly (ethylene glycol) monomethyl ether monomethacryl,
Selected from the group consisting of N-vinyl-N-methylacetamide, vinylmethylsulfone, N-acryloylmorpholine, N-methacryloylmorpholine, N-methacryloylpiperidine, N-alkylacryloylamide, acid functional monomers, and salts thereof. 30. The copolymer of claim 29 formed from at least one monomer. 37. The method of claim 29, wherein the hydrophobic unit is formed from at least one monomer selected from the group consisting of alkylated alkyl acrylates, styrene, t-butyl styrene, substituted acrylamides and methacrylamides. Copolymer of. 38. The copolymer of claim 29, wherein the hydrophobic unit comprises a fluorinated compound. 39. The fluorinated compound is 2- (N-ethylperfluorooctanesulfonamide) ethyl acrylate, 2- (N-ethylperfluorooctanesulfonamide) ethyl methacrylate, hexafluoroisopropyl acrylate, 1H, 1H, 2H, 2H-heptadecafluorodecyl acrylate,
39. The copolymer of claim 38 formed from at least one monomer selected from the group consisting of pentafluorostyrene, trifluoromethylstyrene, fluorostyrene, pentafluoroacrylate, pentafluoromethacrylate, and combinations thereof. . 40. The copolymer of claim 29, wherein the units further comprise at least one unit formed from a high refractive index monomer. 41. The copolymer of claim 29, wherein the units further comprise at least one unit formed from a UV absorbing monomer. 42. The size of the hydrophobic block is such that the block does not cause distortion or scattering of light transmitted through an ophthalmic device containing the copolymer.
30. The copolymer of claim 29, which is well below the wavelength of light. 43. The hydrophobic block and the hydrophilic block have substantially similar refractive indices so that the block does not distort or scatter light transmitted through an ophthalmic device containing the copolymer. 30. The copolymer of claim 29 having 44. The copolymer of claim 29, wherein the hydrophobic block has a crystalline structure and a melting temperature of about 100 ° C. or above the glass transition temperature of the block and below about 250 ° C. . 45. The copolymer of claim 29, wherein the hydrophilic block has a crystalline structure and has a melting temperature of about 100 ° C. or higher than the glass transition temperature of the block and lower than about 250 ° C. 46. The hydrophobic block has an amorphous structure and comprises about 30 to about 2.
30. The copolymer of claim 29 having a glass transition temperature of 00 <0> C. 47. The hydrophobic block has an amorphous structure and comprises about 50 to about 1.
47. The copolymer of claim 46 having a glass transition temperature of 50 ° C. 48. The hydrophobic block has an amorphous structure and comprises about 60 to about 1.
47. The copolymer of claim 46 having a glass transition temperature of 25 ° C. 49. The hydrophilic block has an amorphous structure and comprises about 30 to about 20.
30. The copolymer of claim 29 having a glass transition temperature of 0 <0> C. 50. The hydrophilic block has an amorphous structure and comprises about 50 to about 15.
50. The copolymer of claim 49 having a glass transition temperature of 0 <0> C. 51. The hydrophilic block has an amorphous structure and comprises about 60 to about 12.
50. The copolymer of claim 49 having a glass transition temperature of 5 ° C. 52. The hydrophobic block has a crystalline structure, has a melting temperature of about 100 ° C. or higher than the glass transition temperature of the block and lower than about 250 ° C., and the hydrophilic block is amorphous. 30. The copolymer of claim 29 having a crystalline structure and having a glass transition temperature of about 30 to about 200 <0> C. 53. The hydrophilic block has a crystalline structure and has a melting temperature of about 100 ° C. or higher than the glass transition temperature of the block and lower than about 250 ° C., and the hydrophobic block is 30. The copolymer of claim 29, having an amorphous structure and a glass transition temperature of about 30 to about 200 <0> C. 54. The copolymer of claim 29, wherein at least one of the hydrophobic and hydrophilic units comprises a pendant labile functional group capable of latent crosslinking of the copolymer by covalent crosslinking. 55. a) A step of preparing a block copolymer comprising blocks which self-separate into mutually immiscible phases, the main component comprising blocks containing hydrophilic units at the intended use temperature. , The sub-ingredient comprises a block containing a hydrophobic unit, the hydrophobic block of the sub-ingredient dissociating at an elevated temperature above about 80 ° C. to transfer the copolymer to an ophthalmic device without covalent cross-linking. B) melt processing the copolymer, and c) hydrating the melt processed copolymer to about 35% to about 90% by weight of the total hydrated block copolymer. Obtaining a hydrogel containing water, the melt-processed hydrogel produced by a method comprising: wherein the hydrophobic block of the accessory component is at least about 6%. It supplies an internal hydrophobic bond in an amount sufficient to obtain a dimensionally stable hydrogel at temperatures up to ° C., melt processed hydrogel, characterized in that. 56. The hydrogel copolymer of claim 55, further comprising chemically cross-linking the copolymer to obtain a dimensionally stable hydrogel at temperatures up to at least about 125 ° C. 57. The method of claim 55, wherein at least one of the hydrophobic and hydrophilic units is formed from a monomer containing pendant labile functional groups that can crosslink the copolymer by covalent crosslinking. Copolymer. 58. The copolymer of claim 57, wherein the pendant labile functional group containing monomer is included in an amount of about 2 to about 25 weight percent of the total monomers used to prepare the copolymer. 59. The copolymer of claim 57, wherein the pendant labile functional group containing monomer is included in an amount of about 5 to about 20 weight percent of the total monomers used to prepare the copolymer. 60. The copolymer of claim 55, wherein the hydrogel block copolymer has pendant labile functional groups that can latently crosslink the copolymer by covalent crosslinking. 61. A polymer is provided which is prepared by copolymerizing a) a) a monomer comprising at least one hydrophilic monomer and at least one hydrophobic monomer. B) raising the temperature of the polymer to a temperature above the glass transition temperature of the polymer, c) distributing the polymer into a lens mold, and d) forming a lens from the polymer. E) solidifying the lens in the mold, f) removing the lens from the mold, g) hydrating the lens in an aqueous salt solution to provide about 35 to about 90% by weight.
And a step of forming a contact lens having a water content of 1. 62. The method of claim 61, wherein the temperature of the polymer is raised to a temperature above its glass transition temperature after placing the polymer in the mold. 63. The method of claim 61, wherein the temperature of the polymer is raised to a temperature above its glass transition temperature prior to placing the polymer in the mold. 64. The hydrophobic monomer comprises a fluorinated monomer.
The method according to 1. 65. Prior to introducing the polymer into the contact lens mold,
62. The method of claim 61, further comprising applying a release agent to the mold. 66. The method of claim 61, wherein the polymer is capable of forming a mechanically stable hydrogel when hydrated. 67. A) prepared by polymerizing a) a monomer comprising at least one hydrophilic monomer and at least one hydrophobic monomer in the absence of a substantial amount of a reactive crosslinking agent, Providing a polymer capable of forming a mechanically stable hydrogel when hydrated; b) raising the temperature of the polymer to a temperature above the melting temperature of the polymer; and c) the polymer. To a lens mold; d) forming a lens from the polymer; e) solidifying the lens in the mold; f) removing the lens from the mold; g) the By hydrating the lens in saline solution, about 35 to about 90% by weight
And a step of forming a contact lens having a water content of 1. 68. The method of claim 67, wherein the temperature of the polymer is raised to a temperature above its melting temperature after placing the polymer in the mold. 69. The method of claim 67, wherein the temperature of the polymer is raised to a temperature above its melting temperature prior to placing the polymer in the mold. 70. The melting temperature of the polymer is from about 80 to about 250 ° C.
68. The method of claim 67. 71. The method of claim 67, wherein the melting temperature of the polymer is about 125 to about 200 ° C. 72. Prior to dispensing the polymer into the contact lens mold,
68. The method of claim 67, further comprising applying a release agent to the mold. 73. The method of claim 67, further comprising the step of incorporating a substance into the polymer that is capable of inducing chemical crosslinking of the polymer prior to forming a lens from the polymer. 74. A method comprising: a) copolymerizing at least one hydrophilic monomer and at least one hydrophobic monomer in the presence of at least one monomer having a pendant latent reactive functional group. Forming an uncrosslinked melt-fabricable copolymer having a reactive functional group of the reaction, b) distributing the copolymer into a lens mold, c) forming a lens from the copolymer, d) Forming a covalent crosslink in the copolymer by reacting the functional groups; e) removing the lens from the mold; and f) hydrating the lens to obtain at least 35% by weight. And a step of obtaining a transparent hydrogel lens having a water content. 75. The method of claim 74, wherein the at least one hydrophilic monomer and the at least one hydrophobic monomer are vinyl monomers. 76. The method of claim 74, wherein the at least one monomer having a pendant latent reactive functional group is a vinyl monomer and the functional group is not a vinyl group. 77. The method of claim 74, wherein the functional group is an epoxy, hydroxy, alkenyl, isocyanato, peroxy, perester, anhydride, silane group, or combinations thereof. 78. The reaction of the functional groups is initiated by heat, moisture, acid catalysis, base catalysis, curing agents, UV irradiation, or a combination thereof.
The method of claim 74. 79. The curing agent is a diol, triol, diamine, diisocyanate, dianhydride, chloroanhydride, diepoxide, peroxide, azide,
Selected from the group consisting of benzophenone, and combinations thereof,
79. The method of claim 78. 80. The method of claim 78, wherein the curing agent is combined with the copolymer prior to reacting the functional groups. 81. The curing agent is incorporated into the copolymer by copolymerizing a monomer containing the curing agent during the copolymerization step.
The method described in. 82. The method of claim 74, wherein the monomer having pendant latent reactive functional groups is a photosensitive chromophore. 83. The method of claim 74, wherein the reaction of the functional groups is initiated by irradiating the copolymer with a sufficient amount of actinic radiation. 84. The method of claim 74, wherein the functional group reaction is performed after hydrating the lens. 85. Providing a copolymer wherein the uncrosslinked copolymer comprises a block containing hydrophobic units, the block dissociating at an elevated temperature above about 80 ° C. to allow it to be thermoprocessed into an ophthalmic device. 75. and the block is capable of providing a sufficient amount of internal hydrophobic bonds to provide a dimensionally stable hydrogel at temperatures of at least about 60 ° C. when the copolymer is hydrated. The method described. 86. a) providing a solid crosslinkable polymer that is substantially chemically uncrosslinked, b) introducing the polymer into a lens mold, and c) heat treating the polymer. Taking the shape of the lens mold by: d) forming covalent crosslinks in the polymer while maintaining the shape of the lens mold; e) removing the lens from the mold; f) Hydrating the lens to form an ophthalmic device having a water content greater than 35% by weight of the hydrated device. 87. The method of claim 86, wherein the step of heat treating the polymer comprises melting the polymer prior to introducing it into the lens mold. 88. The method of claim 86, wherein the cross-linking step is performed after removing the lens from the lens mold. 89. The method of claim 86, wherein the cross-linking step is initiated by heat applied when heat treating the polymer. 90. The crosslinking step comprises heat, moisture, acid catalysis, base catalysis,
87. The method of claim 86, initiated by at least one of UV irradiation, oxidation and reactants. 91. The method of claim 86, further comprising initiating crosslinking by treating the polymer with a curing agent. 92. The curing agent is selected from the group consisting of diamines, diols, triols, diisocyanates, dianhydrides, anhydrides, diepoxides, peroxides, azides, benzophenones, and combinations thereof. Item 91. The method according to Item 91. 93. The method of claim 92, wherein the curing agent is glycerin. 94. The method of claim 91, wherein the curing agent is combined with the polymer prior to reacting the functional groups. 95. The curing agent is incorporated into the polymer by copolymerizing a monomer containing the curing agent during the copolymerization step.
The method according to 1. 96. The polymer contains labile functional groups capable of reacting and cross-linking after copolymerizing the polymer, wherein the functional groups are epoxy, hydroxy, alkenyl, isocyanato, peroxy, perester, anhydride. 88. The method of claim 86, which is a silane group, or a combination thereof. 97. The hydration step comprises allowing the lens to be in a saline solution for a time sufficient to cause the lens to have a water content of about 35 to about 90 wt% based on the total weight of the hydrated lens. 87. The method of claim 86, comprising soaking. 98. The non-crosslinked polymer comprises a main component, a subcomponent,
A block that self-separates into mutually immiscible phases, at the intended use temperature, the main component comprises a block of hydrophilic units, the subcomponent comprises a block of hydrophobic units, and the subcomponent Obtain a polymer that can be thermoprocessed into an ophthalmic device by dissociating the block of at least 80 ° C. at an elevated temperature, and the sub-component hydrophobic monomer block has at least about when the polymer is hydrated. 87. The method of claim 86, wherein a sufficient amount of internal hydrophobic bonds can be provided to provide a dimensionally stable hydrogel at temperatures up to 60 <0> C. 99. a) providing a solid polymer that is substantially chemically crosslinked, and b) an amount sufficient to render the polymer substantially chemically uncrosslinked. A step of opening a cross-link, c) a step of introducing the polymer into a lens mold, d) a step of heat-treating the polymer to take the shape of the lens mold, and e) the shape of the lens mold as it is. Forming new covalent crosslinks in the polymer, f) removing the lens from the mold, and g) hydrating the lens to provide water content above 35% by weight of the hydrated device. Forming an ophthalmic device having a refractive index, and a method of manufacturing an ophthalmic device comprising a hydrogel polymer comprising: 100. The chemical cross-linking comprises a disulfide bond.
9. The method according to 9. 101. The method of claim 99, wherein the polymer comprises chemical cross-linking of disulfide bonds introduced by copolymerizing a difunctional monomer containing the disulfide bonds. 102. The method of claim 101, wherein the polymer is prepared by copolymerizing monomers of disulfide-containing bisacrylamide, disulfide-containing dimethacrylate or disulfide-containing diacrylate early in the copolymerization. 103. The method of claim 102, wherein the disulfide-containing monomer comprises N, N'-cystamine-bis-acrylamide. 104. The method of claim 99, wherein the cross-links are opened by chemical reduction.
The method described in. 105. The method of claim 104, wherein the chemical reduction is performed by reaction with dithiothreitol. 106. The method of claim 99, wherein the cross-linking is accomplished by chemical oxidation while in the lens mold shape. 107. The method of claim 106, wherein the chemical oxidation is performed by reaction with cystamine or molecular oxygen. 108. a) a thin film of polymeric material; b) introducing the film between halves of a temperature controlled mold; and c) halving the film in the mold. Forming a film in the shape of a contact lens precursor by applying sufficient force and heat for a sufficient period of time, and d) opening the half mold. A method of manufacturing a hydrogel contact lens, comprising the steps of: e) removing the lens precursor from the half mold, and f) forming a hydrogel contact lens by hydrating the lens precursor. 109. The method of claim 108, wherein the thin film is crosslinked but still thermoformable. 110. The method of claim 108, wherein the heat provides sufficient crosslinking to render the lens precursor non-thermoformable. 111. The polymeric material contains labile functional groups capable of reacting and crosslinking after copolymerizing the polymer, wherein the functional groups are epoxies,
Hydroxy, alkenyl, isocyanato, peroxy, perester, anhydride,
109. The method of claim 108, which is a silane group or a combination thereof. 112. The method of claim 111, wherein the functional group reaction is initiated by heat, moisture, acid catalysis, base catalysis, curing agents, UV irradiation, or combinations thereof. 113. The method of claim 108, further comprising applying a release agent to the mold prior to introducing the polymer into the contact lens mold. 114. The method of claim 108, further comprising the step of subjecting the precursor to at least one finishing treatment prior to hydrating the lens precursor into a lens. 115. The method of claim 114, wherein the finishing process comprises at least one of trimming, edging and polishing. 116. a) applying heat to melt the polymeric material; b) distributing the melted polymer into the cavity of the lens mold; c) retaining the melted polymer in the shape of the lens mold. Solidifying in the lens mold for a sufficient time to: d) opening the lens mold; e) removing the lens from half the mold; and f) the lens precursor. Forming a hydrogel contact lens by hydrating the body; 117. The method of claim 116, further comprising applying a mold release agent to the mold prior to introducing the polymer into the contact lens mold. 118. The method of claim 116, further comprising subjecting the precursor to at least one finishing treatment prior to hydrating the lens precursor into a lens. 119. The method of claim 118, wherein the at least one finishing process comprises trimming, edging or polishing. 120. a) dissolving the polymeric material in an organic solvent; b) mixing the polymeric material with a curing agent; and c) dispensing the polymeric material and the curing agent into a lens mold cavity. D) by causing a crosslinking reaction between the polymeric material and a curing agent,
Solidifying the reacted mixture to retain the shape of the lens mold; e) opening the lens mold; f) removing the lens from half the mold; and g) removing the lens. Forming a hydrogel contact lens by hydration; and a method for producing a hydrogel contact lens, comprising: 121. The method of claim 120, wherein the mixing step is performed in the cavity. 122. The method of claim 120, further comprising applying a release agent to the mold prior to introducing the polymer into the contact lens mold. 123. The method of claim 120, further comprising the step of subjecting the precursor to at least one finishing treatment prior to hydrating the lens precursor into a lens. 124. The method of claim 123, wherein the at least one finishing process comprises trimming, edging or polishing. 125. A physically crosslinked hydrogel comprising a branched copolymer containing hydrophobic side chains substantially free of chemical crosslinks and a hydrophilic backbone, the hydration thereof. A hydrogel, characterized by being suitable for use in a thermal processing or molding process for making an ophthalmic device in the untreated state. 126. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophobic side chains, the side chains comprising about 2-90% by weight of the total dry hydrogel. 126. The hydrogel of claim 125. 127. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophobic side chains, the side chains comprising about 5-60% by weight of the total dry hydrogel. 126. The hydrogel of claim 125. 128. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophobic side chain, wherein the side chain is 3
126. The hydrogel of claim 125 having a molecular weight of 00-100,000. 129. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophobic side chain, wherein the side chain is 5
127. The hydrogel of claim 125, having a molecular weight of 00-50,000. 130. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophobic side chain, wherein the side chain is 1
127. The hydrogel of claim 125, having a molecular weight of 1,000 to 10,000. 131. The hydrogel of claim 125, wherein the unhydrated hydrogel has a weight average molecular weight of about 10,000 to about 1,000,000. 132. The hydrogel of claim 125, wherein the unhydrated hydrogel has a weight average molecular weight of about 50,000 to about 500,000. 133. A physically crosslinked hydrogel comprising a branched chain copolymer containing hydrophilic side chains substantially free of chemical crosslinks and a hydrophobic backbone, the hydration thereof. A hydrogel, characterized by being suitable for use in a thermal processing or molding process for making an ophthalmic device in the untreated state. 134. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophilic side chain, the side chain comprising about 2 to 90% by weight of the total dry hydrogel. 138. The hydrogel of claim 133. 135. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophilic side chain, the side chain comprising about 5-60% by weight of the total dry hydrogel. 138. The hydrogel of claim 133. 136. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophilic side chain, wherein the side chain is 3
136. The hydrogel of claim 133 having a molecular weight of 00-100,000. 137. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophilic side chain, wherein the side chain is 5
138. The hydrogel of claim 133, having a molecular weight of 00 to 50,000. 138. The branched copolymer is prepared by copolymerizing a monomer containing a macromer containing the hydrophilic side chain, wherein the side chain is 1
138. The hydrogel of claim 133, having a molecular weight of 1,000 to 10,000. 139. The hydrated hydrogel comprises from about 10,000 to about 1,000.
138. The hydrogel of claim 133, having a weight average molecular weight of 1,000. 140. The hydrogel of claim 133, wherein the unhydrated hydrogel has a weight average molecular weight of about 50,000 to about 500,000. 141. A blend of at least two different miscible polymers,
A polymer composite hydrogel material comprising about 35-85% water by weight of the total hydrogel, wherein at least one of said copolymers comprises a block polymer comprising blocks which self-separate into mutually immiscible phases. The main component comprises a block containing a hydrophilic unit, the sub-component comprises a block containing a hydrophobic unit, and the hydrophobic block of the sub-component dissociates at an elevated temperature above about 120 ° C. Allows the polymer to be heat processed into an ophthalmic device in the absence of covalent crosslinks, the other polymer containing a large amount of hydrophobic units, and the blend of polymers being melt processed into an ophthalmic device. The material is characterized in that it is suitable for 142. A polymer comprising a backbone and at least one grafted side chain, the polymer being melt processable at a temperature of about 50-300 ° C., and about 35 of the fully hydrated polymer. A polymer capable of forming a hydrogel having a water content of about 90% by weight and being optically transparent. 143. The polymer of paragraph 142, wherein the polymer is substantially free of crosslinkers. 144. a) about 20-90% by weight of the total monomers of at least one hydrophilic monomer and about 5-80% by weight of the total monomers of at least one copolymerizable hydrophobic monomer; Preparing a precursor to the backbone by polymerizing a monomer comprising about 0.5 to 50% by weight of the monomer, and at least one copolymerizable monomer having a latent reactive functional group; b. ) Polymerizing a monomer comprising about 20-100% by weight of the total monomers of at least one hydrophobic monomer and about 0-80% by weight of the total monomers of at least one copolymerizable hydrophilic monomer. A precursor to the side chain is prepared by: c) binding the precursor of the main chain to a unit bonded to the precursor of the side chain. The polymer of claim 142. 145. The polymer of claim 144, wherein the monomers having latently reactive functional groups are present in an amount of about 0.5-30% by weight of total monomers. 146. The polymer of claim 144, wherein the monomers having latently reactive functional groups are present in an amount of about 1-20% by weight of total monomers. 147. The polymer of claim 144, wherein the latently reactive functional group is capable of initiating polymerization of monomers in the presence of at least one catalyst. 148. The latently reactive functional group comprises a halocarbon functional group.
154. The polymer of claim 144. 149. The polymer of claim 144, wherein the grafted side chains are prepared by polymerizing a monomer with a halocarbon initiator in the presence of a metal halide catalyst. 150. The polymer of paragraph 144, wherein the grafted side chains comprise functional groups at the ends of the chains furthest from the backbone. 151. The polymer of paragraph 150, wherein the functional group is an alkoxide or an aryl oxide. 152. The polymer of claim 150, wherein the functional groups are capable of inducing latent crosslinking in the polymer. 153. Formulas I and II: Where R ¹ and R ³ are independently H or CH ₃ , R ² is NR ⁵ R ⁶ or OR ⁷ , and R ⁴ is C ₁ -C ₅₀₀ alkyl, C _6- C ₅₀₀ aryl, C (O) NR ⁸ R ⁹ or C (O) is oR ^10, R ⁵ _{is, H, CH 3, C 1} ~C 500 alkyloxy, C ₁ -C ₅₀₀ alkenyloxy, C ₁ ~ C ₅₀₀ alkyl amino or C ₁ -C ₅₀₀ alkenyl amino, R ⁶ _{is, H, CH 3, CH 2} CH 3, C 1 ~C 500 alkyloxy, C ₁ -C ₅₀₀ alkenyloxy, C ₁ -C ₅₀₀ alkylamino or C ₁ -C ₅₀₀ alkenyl amino, R ⁷ is, H, C ₁ ~C ₅₀₀ alkyloxy, C ₁ -C ₅₀₀ alkenyloxy, C ₁ ~
A C ₅₀₀ alkyl amino or C ₁ -C ₅₀₀ alkenyl amino, R ⁸ is, H, a CH _3, C ₁ ~C ₅₀₀ alkyl or C ₆ -C ₅₀₀ aryl, R ⁹ is, C ₃ -C ₅₀₀ alkyl , C ₆ -C ₅₀₀ aryl, polysiloxane or formula I
A chain comprising units of I, R ¹⁰ is, H, C ₁ -C ₅₀₀ alkyl, optionally _{- (CH 2 CH 2 N (} CH 2 CH 3) SO 2) - C 1 containing linking groups - A polymer containing units of C ₅₀₀ fluoroalkoxy or a chain containing units of formula II, which is melt processable at temperatures of about 50 to 300 ° C.
A polymer capable of forming a hydrogel having a water content of about 90% by weight and being optically transparent. 154. In its unhydrated state, about 20-90% by weight.
154. The polymer of claim 153 comprising units of formula I of: and about 5-80% by weight of units of formula II. 155. In its unhydrated state, about 35-80% by weight.
154. The polymer of claim 153, comprising units of formula I of: and about 15-50% by weight of units of formula II. 156. In its unhydrated state, about 45-65% by weight.
154. The polymer of claim 153, comprising units of formula I of: and about 20-40% by weight of units of formula II.