Ophthalmic viscoelastic device and lysis device

Abstract

The present invention relates to an ophthalmic viscoelastic device comprising at least one viscoelastic polymer (10) cleavable into polymer chains (12) having a lower molecular weight. The viscoelastic polymer (10) comprises at least two polymer chains (12) connected to each other by at least one thermally and / or photochemically cleavable group (14). The invention also relates to a cleavage device (16) comprising means for cleavage of at least one thermally and / or photochemically cleavable group (14) of such an ophthalmic viscoelastic device.

Description

Technical Field

[0001] The present invention relates to a biodegradable ophthalmic viscoelastic device and a pyrolysis device for degrading such an ophthalmic viscoelastic device. Existing technology

[0002] Cataracts are a common condition, especially among older adults, in which the eye's lens gradually becomes opaque. This clouding of the natural lens leads to a loss of visual acuity. Cataract surgery is required to restore vision. The standard procedure used to remove the cloudy lens nucleus to create a capsular bag for inserting an artificial intraocular lens (IOL) is called phacoemulsification, which is performed using a device that generates ultrasonic vibrations.

[0003] Prior to phacoemulsification, the anterior chamber is typically filled with an ophthalmic viscoelastic device (OVD). Viscoelastic OVDs serve as surgical aids to protect intraocular tissues (e.g., protecting the corneal endothelium during phacoemulsification), as spacers (e.g., supporting the anterior chamber), and to facilitate intraocular procedures, such as controlled capsulorhexis. However, such OVDs are also used in other ocular surgeries, such as corneal transplantation or glaucoma surgery.

[0004] OVD is typically an aqueous solution containing a viscoelastic polymer such as hyaluronic acid (HA), chondroitin sulfate (CS), hydroxypropyl methylcellulose (HPMC), or mixtures thereof. Viscoelastic compositions can vary in terms of the molecular weight of the polysaccharide dissolved in the solution, the concentration of the polysaccharide, and the viscosity of the solution. Rheological properties are highly dependent on the concentration and molecular weight of the polymer.

[0005] Typically, a distinction is made between two types of OVDs. High-viscosity cohesive OVDs maintain space and build up pressure. For example, they are used to dilate the pupil before opening the anterior capsule of the lens (capsulotomy). Cohesive OVDs are composed of high molecular weight polymers.

[0006] In contrast, low-viscosity dispersed OVDs encapsulate and protect tissue. One of the most important applications is the formation of an adhesive polymer barrier with a thickness of approximately 100 µm to approximately 1 mm between the corneal endothelium in the anterior chamber. Compared to cohesive OVDs, dispersed OVDs contain polymer chains with lower molecular weights.

[0007] Both types of OVDs are typically injected at the beginning of the procedure. During lens breakage, they may escape from the incision. For this reason, they are replenished before implanting an artificial lens, as the anterior chamber must be dilated for this step. After surgery, the OVD must be completely removed from the eye. The degradation of the OVD and its removal via natural drainage would take too long. During this period, the patient will experience significantly increased intraocular pressure. This is not only painful but can also lead to a high risk of developing glaucoma. Summary of the Invention

[0008] The object of this invention is to provide an ophthalmic viscoelastic device for use in the context of ophthalmic surgery, which reduces the risk of increased intraocular pressure after ophthalmic surgery. Another object of this invention is to provide a lysis device for such an ophthalmic viscoelastic device.

[0009] According to the invention, this objective is achieved by the ophthalmic viscoelastic device as claimed in claim 1 and the lysis device as claimed in claim 9. Advantageous configurations having suitable forms of the invention are specified in the dependent claims; advantageous configurations of each aspect of the invention should be considered as advantageous configurations of corresponding other aspects of the invention.

[0010] A first aspect of the invention relates to an ophthalmic viscoelastic device comprising at least one viscoelastic polymer capable of being fragmented into lower molecular weight polymer chains. According to the invention, the viscoelastic polymer comprises at least two polymer chains bonded to each other via at least one thermally and / or photochemically cleavable group. In other words, at least one viscoelastic polymer of the ophthalmic viscoelastic device (OVD) of the present invention consists of two or more shorter polymer chains, each bonded to each other via at least one thermally and / or photochemically cleavable group, through which a predetermined “breakpoint” is achieved. Compared to, for example, hydrolyzable polymers, the viscoelastic polymer of the OVD of the present invention can be substantially stable under biological conditions in the capsular bag or in the patient’s eye, and can be specifically fragmented only after external thermal and / or photochemical stimulation. Furthermore, fragmenting the viscoelastic polymer into shorter polymer chains preferably does not produce any pharmaceutically active fragments. Instead, the viscoelastic polymer can be specifically cleaved into shorter polymer chains or oligomer chains with corresponding lower molecular weights and different rheological properties by thermal and / or photochemical stimulation. These shorter polymer chains or oligomer chains are small enough to be rapidly transported and disintegrated by the body through the trabecular meshwork or Schlemm's canal. Since the OVD of this invention can thus dissolve or decompose in the eye and can be rapidly transported and disposed of by the body via natural drainage pathways, removal of the OVD after surgery is no longer necessary. This saves time for doctors and operating room staff and allows for more procedures to be performed within a given timeframe. Finally, this type of OVD improves patient safety by reducing the likelihood of increased intraocular pressure or trabecular meshwork problems after surgery. In its simplest configuration, cleavage can be performed without additional injection or invasive manipulation, for example, by irradiation with sunlight or ambient light or with light of a specific wavelength or wavelength range. In the context of this disclosure, “a / an” should generally be understood as an indefinite article, meaning that it is always understood as “at least one / an” unless there is an explicit indication to the contrary. Conversely, “a / an” can also be understood as meaning “only one / an”.

[0011] In an advantageous configuration of the invention, the polymer chain has a molar mass between 70 kDa and 200 kDa, particularly between 76 kDa and 190 kDa, and / or the viscoelastic polymer has an average molecular weight of at least 0.5 MDa, particularly at least 2.5 MDa. All measures and properties mentioned individually or in any combination have the effect that the polymer chain or fragments formed after the thermally and / or photochemically cleavable groups have a sufficiently small size to reliably and completely, or at least substantially completely, pass through the pores of the trabecular mesh or Schlemm's tube and can be removed from the eye.

[0012] A further benefit arises from the fact that the at least one viscoelastic polymer comprises at least one building unit from the group consisting of hyaluronic acid, alginate, chitosan, methylcellulose, hydroxypropyl methylcellulose (HPMC), chondroitin sulfate, collagen, and gelatin. This includes all derivatives and salts of the polymer, such as hyaluronic acid salts, alginates, etc. In the context of this disclosure, a building unit refers to a monomer, oligomer, or polymer structural element or polymer chain of the viscoelastic polymer. The cleavage may preferably cleave the viscoelastic polymer back into these original building units or, consequently, polymer chains composed of these building units. It may also be the case that the viscoelastic polymer consists only of one of the building units, i.e., for example, only of hyaluronic acid building units, which are indirectly crosslinked (i.e., via spacers, crosslinking agents, or other derivatizations) or directly crosslinked via thermally and / or photochemically crosslinking groups to form the viscoelastic polymer. Conversely, it may also be the case that the viscoelastic polymer consists of two or more different building units (i.e., for example, hyaluronic acid building units and HPMC building units, etc.).

[0013] In another advantageous embodiment of the invention, the at least one viscoelastic polymer comprises polymer chains bonded to each other end-to-end via the at least one thermally and / or photochemically cleavable group and / or via side chain sites. In other words, the viscoelastic polymer is formed of two or more shorter polymer chains, wherein the individual polymer chains are linearly crosslinked to each other via corresponding terminal thermally and / or photochemically cleavable groups. This allows for particularly precise pre-determining of the polymer chain size after the cleavable groups have cleaved, a size that enables particularly reliable transport of polymer fragments away via the aqueous humor and trabecular meshwork. In turn, the molar mass of the viscoelastic polymer can thus be particularly easily adjusted, and particularly long polymer chains are also possible, making viscoelastic polymers with exceptionally high molar masses readily available. Alternatively or additionally, the polymer chains are connected to each other via side chain sites. In other words, the polymer chains have one or more non-terminal thermally and / or photochemically cleavable groups, through which crosslinking with one or more other polymer chains is achieved. Non-terminal side chain sites in the polymer chains may also be referred to as “internal sites” or “internal monomers.” These are sites between the chain ends other than the polymer end groups. End groups are the outermost monomers at each end of the chain. Internal monomers typically have higher mobility than end groups and therefore play a significant role in the polymer's kinetics and properties. Furthermore, this can form a three-dimensional network, thereby tuning the rheological properties of viscoelastic polymers in addition to their degradability. A further step could be to crosslink individual polymer chains via additional functional groups, provided that sufficient degradability and outward transport are ensured after the thermal and / or photochemically unstable groups have cleaved. In this way, the viscoelastic properties of viscoelastic polymers can also be tuned with particularly precise control.

[0014] In another advantageous configuration of the invention, the ophthalmic viscoelastic device takes the form of a cohesive or dispersed ophthalmic viscoelastic device. Cohesive OVDs can be used during ophthalmic surgery to fill the space between the lens and cornea and stabilize intraocular pressure, providing several benefits that can help improve the safety and effectiveness of ophthalmic surgery. Due to the biodegradability of the invention, there is no need to remove the OVD from the eye after ophthalmic surgery. Furthermore, viscoelastic polymers with particularly high average molecular weights can be produced according to the invention, which allows for particularly good space retention. Dispersed OVDs can reliably generate an adhesive polymer barrier during ophthalmic surgery. Preferably, the viscoelastic polymer in this case has a molecular weight of up to 2 MDa, particularly about 1 MDa, which corresponds to an average of about 1250 monomers in the case of hyaluronic acid. Furthermore, under standard conditions (25°C, 1 bar), the zero-shear viscosity does not exceed 100 Pas, particularly not more than 50 Pas. It will be apparent that the definition of standard conditions does not preclude the possibility that the OVD or its components may also have specified properties at different temperatures and / or pressures.

[0015] Alternatively or additionally, the concentration of at least one viscoelastic polymer, based on the total volume of the ophthalmic viscoelastic device, is between 0.1 mg / ml and 50 mg / ml. This also allows the properties of the OVD to be optimized for the corresponding end use.

[0016] Alternatively or additionally, the ophthalmic viscoelastic device comprises at least one therapeutic agent, particularly analgesics and / or antioxidants, wherein the therapeutic agent is preferably covalently bonded to and / or embedded in the at least one viscoelastic polymer via at least one thermally and / or photochemically cleavable group. This enables preferably controlled delivery of the therapeutic agent (which can optionally be controlled by the degradation rate of the viscoelastic polymer), thereby further facilitating ophthalmic surgery. The therapeutic agent may be covalently bonded to the at least one viscoelastic polymer, embedded in the polymer, or dissolved in OVD. In the case of covalent bonding, the therapeutic agent can also be attached via the same thermally and / or photochemically cleavable group as the polymer chain and released by means of the same thermal and / or photochemical stimulation without additional measures. Alternatively, the therapeutic agent may be attached by means of different groups and released accordingly via different stimuli. This allows for controlled release of the therapeutic agent without the need to cleave the viscoelastic polymer.

[0017] Further benefits arise from the fact that ophthalmic viscoelastic devices contain stabilizers, particularly free radical scavengers, and / or magnetic particles, particularly micron-sized and / or nano-sized particles. The stabilizers reliably prevent premature and undesirable decomposition of the viscoelastic polymer and improve the storage stability of the OVD. Alternatively or additionally, the viscoelastic polymer can be decomposed or degraded by adding magnetic particles, particularly micron-sized and / or nano-sized particles, to the OVD and subjecting them to an external magnetic field to decompose the viscoelastic polymer; this can be referred to as magnetic field-assisted degradation. The basic idea is to mix magnetic particles, typically composed of magnetite or other ferromagnetic materials, with the viscoelastic polymer and then apply an external magnetic field to the mixture. The magnetic field induces an alternating current in the microspheres, which generates heat through hysteresis. The heat generated by the magnetic microspheres then causes the surrounding viscoelastic polymer to be thermally decomposed and degraded into polymer chains. Alternatively, the heat generated by the magnetic particles can also accelerate the photochemical degradation of the viscoelastic polymer by increasing the rate of chemical reactions. The specific conditions required for magnetic field-assisted degradation depend on the type of viscoelastic polymer used, the size and concentration of the magnetic particles, and the strength and frequency of the magnetic field. Typically, the magnetic field must be strong enough to induce alternating current in the magnetic particles, but preferably not strong enough to cause the magnetic particles to agglomerate and form clumps that could prevent the uniform degradation of the viscoelastic polymer.

[0018] In another advantageous embodiment of the invention, at least one thermally and / or photochemically cleavable group is selected from compounds that can be coupled or linked via [2+2] cycloaddition and / or click chemistry. In other words, individual polymer chains are preferably covalently bonded to thermally and / or photochemically cleavable groups, which are then coupled or linked to each other via [2+2] cycloaddition and / or click chemistry. The coupling and / or cleavage can also be reversible in principle. [2+2] cycloaddition (also known as 1,2 cycloaddition) describes the photochemical process in which an alkenyl group with an activated double bond forms a cyclobutane derivative. Useful compounds for this process include, for example, ketenes, dienes, cinnamic acid, coumarins, and also vinyl fluoride and vinyl chloride. Stereochemistry can be predicted by applying the Woodward-Hoffmann rule based on orbital symmetry. There is a distinction between thermally permissible and photochemically permissible [2+2] cycloadditions. Thermal [2+2] cycloadditions can occur in three different ways: concerted, radical, or ionic. Orbital symmetry plays no role in radical or ionic processes compared to concerted reactions. Most concerted [2+2] cycloadditions are photochemically permissible electrocyclic reactions and are described by the Woodward-Hoffmann rule. Click chemistry refers to a class of chemical reactions characterized by rapid, efficient, and specific reactions between two co-reactants to form new compounds. The reactions are typically highly selective and yield products in high yields. Click chemistry is particularly well-suited for the production of functionalized molecules and materials used in biotechnology and medicine. An example of a click chemical reaction is the Cu(I)-catalyzed azide-alkyne cycloaddition (also known as the "Huisgen cycloaddition"). This example uses a catalyst in a rapid and specific reaction to attach an azide group to an alkyne group and release nitrogen to form a 1,2,3-triazole ring. This reaction is very useful for the synthesis of functionalized molecules and polymers because both alkyne and azide groups can be introduced into multiple molecules. Click chemistry has been found to be very useful because it provides a simple, efficient, and selective way to chemically link compounds together. The main benefits of click chemistry are its high efficiency and selectivity, and its operation under mild conditions. Another important advantage of click reactions is their bioorthogonality, meaning they are compatible with biological systems. Azide and alkyne groups are not present in natural systems, and therefore click reactions are a very useful method for binding molecules to polymers or oligomers, such as hyaluronic acid (HA) and other viscoelastic polymers, or to corresponding building blocks of such viscoelastic polymers.

[0019] In another advantageous embodiment of the invention, the ophthalmic viscoelastic device is stored in an insulated container and / or an opaque container. As a result, the shelf life of the OVD can be advantageously increased, and premature or undesirable decomposition can be reliably avoided.

[0020] A second aspect of the invention relates to a pyrolysis device comprising means for pyrolyzing at least one thermally and / or photochemically pyrolyzable group of an ophthalmic viscoelastic device according to a first aspect of the invention. With this pyrolysis device, thermal and / or photochemical stimulation can be generated, leading to the pyrolysis of the unstable groups of the viscoelastic polymer of the OVD, and thus the viscoelastic polymer decomposes into corresponding shorter polymer chains that can be naturally transported away from the patient's eye. Further features and their benefits can be inferred from the description of the first aspect of the invention; advantageous configurations of each aspect of the invention should be considered advantageous embodiments of the corresponding other aspects of the invention.

[0021] In an advantageous embodiment of the invention, the lysis device includes a light source as a means of generating light with a wavelength having photochemically cleaved at least one group. Optionally, a light guide may be provided to direct the light generated by the light source to the patient's eye. The lysis device may be positioned on, for example, a surgical microscope or integrated into a surgical microscope, and during ophthalmic surgery, the patient's eye may be exposed to light of a predetermined wavelength or range of wavelengths over a certain area and / or at a specific point or along an irradiation path to induce the photochemical decomposition of one or more groups of the viscoelastic polymer. Alternatively or additionally, the lysis device may take the form of a contact lens, a pair of glasses, or more generally a device that can cover at least some areas of the patient's eye. The provided light source may be, for example, optionally a ring-shaped LED light. The patient may then wear the lysis device after surgery (e.g., during the recovery phase). The light generated by the lysis device is then transmitted to the anterior chamber and cleaves the viscoelastic polymer of the OVD. This can advantageously be done without the intervention of a surgeon and is convenient for the patient if the lysis of the viscoelastic polymer takes longer than a few seconds. Alternatively or additionally, the pyrolysis apparatus includes a magnetic device for generating a magnetic field, through which the magnetic particles of the ophthalmic viscoelastic device can be heated to pyrolyze at least one functional group. Depending on the functional group used, it can thus be pyrolyzed by purely thermal means. Alternatively, magnetic heating can be used to accelerate the photochemical pyrolysis reaction rate.

[0022] Further features of the invention will be apparent from the claims, the drawings, and the description of the drawings. Features and combinations of features mentioned in the foregoing description, and features and combinations of features mentioned in the following description of the drawings and / or shown only in the drawings, can be used not only in the corresponding specified combinations, but also in other combinations without departing from the scope of the invention. Therefore, the invention should also be considered to include and disclose configurations of the invention that are not explicitly shown and illustrated in the drawings, but are apparent from the illustrated configurations and can be created by individual combinations of features from these illustrated configurations. The disclosure should also be considered to extend to embodiments and combinations of features that do not thus have all the features of the independent claims as stated in the initial wording. Furthermore, the disclosure should be considered to extend to embodiments and combinations of features, particularly those features set forth above in dependent references beyond or departing from the claims. In the drawings:

[0023] Figure 1 A schematic diagram of the production steps of the viscoelastic polymer in the ophthalmic viscoelastic device of the present invention in a working example;

[0024] Figure 2 A schematic diagram of the production steps of the alternative viscoelastic polymer for the ophthalmic viscoelastic device of the present invention in another working example;

[0025] Figure 3 [2+2] cycloaddition reaction of coumarin-substituted polymer chains;

[0026] Figure 4 [2+2] cycloaddition reaction of cinnamic acid-substituted polymer chains;

[0027] Figure 5 A schematic diagram of the repeating disaccharide unit of hyaluronic acid;

[0028] Figure 6 A diagram of the pyrolysis apparatus in a working example, and

[0029] Figure 7 A diagram of the pyrolysis apparatus in another working example. Detailed Implementation

[0030] Ocular viscoelastic devices (OVDs) are important aids in cataract surgery, among other procedures. When the eye is 26 (… Figure 6When the eye is cut open, aqueous humor drains from the eye 26. To facilitate cataract surgery, an OVD (Optical Vacuum Discharge Device) is inserted into the eye 26 to create space in the anterior chamber 24. OVDs suitable for creating space typically have relatively high viscosity (cohesive OVD type, viscosity > 60,000 mPas). Another function of the OVD is to coat endothelial cells, for which lower viscosity OVDs are designed (dispersed OVD type, viscosity < 60,000 mPas). Viscosity values ​​can be determined under the conventional standard conditions for OVDs (25°C, 1 bar).

[0031] Both types of OVDs are injected at the start of the procedure. During lens breakage, they may overflow from the incision. For this reason, they are replenished before implantation of an artificial lens (IOL), as the anterior chamber must be dilated for this step. After surgery, the OVDs must be completely removed from the eye. The body cannot drain conventional OVDs naturally through the trabecular meshwork like aqueous humor. If OVDs remain in the eye after surgery, they obstruct the eye's natural drainage, potentially leading to increased intraocular pressure (IOP), which is very painful for the patient and also carries the risk of glaucoma development.

[0032] Figure 1 A schematic diagram of the production steps of the viscoelastic polymer 10 of the ophthalmic viscoelastic device (OVD) of the present invention is shown in a working example. In this procedure, polymer chains 12 are first provided, each having a chain length that allows for rapid transport out of the body (i.e., in the patient's eye) via natural drainage pathways such as the trabecular meshwork or Schlemm's canals without a significant increase in intraocular pressure (IOP). The polymer chains 12 (also referred to as building blocks) can, in principle, have the same or different lengths or (average) molar masses. In step Ia, the polymer chains 12 are derivatized and provided with functional groups 14. In the working example shown, functional groups 14 are each attached to both ends of a separate polymer chain 12. In step Ib, the functional groups 14 are then end-to-end coupled, thereby allowing the production of viscoelastic polymers 10 of virtually any length, depending on the reaction scheme. For example, viscoelastic materials with particularly high molecular weights exceeding 3 MDa can be produced, which are currently unavailable via established production pathways. The functional groups 14 at both ends of each polymer chain 12 can typically be different or have the same length, provided they can react with each other in the described manner. This generally means that either only head-to-tail connections are possible, or head-to-head, head-to-tail, and tail-to-tail connections are possible. In this working example, the head and tail groups 14 are different, making only head-to-tail connections possible. Depending on the type of building unit 12 and functional group 14, different chemical reaction pathways are possible. Depending on the reaction type, reaction step Ib can be photochemically (h The process is carried out by either thermal (ν) or thermal (Δ) methods, and preferably reversibly, so that polymer 10 can be broken down into individual polymer chains 12. Photochemical reactions are preferred in principle, and these photochemical reactions can be thermally assisted. In some embodiments according to step Ic, the viscoelastic polymer 10 may optionally be thermally and / or photochemically cleaved, wherein functional groups 14 are further destroyed, modified, or irreversibly cleaved, and thus this step is irreversible. Both scenarios have advantages in terms of production method and sensitivity to light exposure. In the case of photochemical cleavage, the desired wavelength is preferably in the region blocked by the cornea, i.e., below about 300 nm. This cleavage or activation wavelength can be varied by corresponding substituents on the shown molecular structure, particularly increasing to, for example, about 400 nm or greater. Therefore, neither the cornea nor the IOL will act as a barrier. This also applies to, for example... Figure 4 The compound shown.

[0033] Figure 2 A schematic diagram of the production steps of an alternative viscoelastic polymer 10 for the ophthalmic viscoelastic device of the present invention is shown in another working example. Compared to the aforementioned working example, the polymer chain 12 is first chemically modified in optional step IIa and crosslinked in step IIb. The crosslinking is not terminal or end-to-end, but via the side chains of the polymer chain 12. This reaction is primarily concentration-dependent and is preferably controlled in such a way that the number of reactions or crosslinks per polymer chain of the viscoelastic polymer 10 is limited to 1, 2, or 3. To achieve chain growth that is greater than the simple multiplication of the molecular weight, each polymer chain 12 should provide at least two crosslinking sites, which may be located at the terminal position ( Figure 1 ), lateral position ( Figure 2 (or any combination thereof).

[0034] The concepts described herein are not limited to implementation using specific chemical groups. Useful starting points could be structures suitable for [2+2] cycloaddition reactions, such as coumarin or cinnamic acid, as these compounds and the reactions themselves are known and reliably implemented. Furthermore, there is abundant data available regarding biocompatibility in the capsule, non-invasive initiation of the reaction by light exposure, and alterations in chemical modification and absorption maxima.

[0035] Figure 3The [2+2] cycloaddition reaction of a coumarin-substituted polymer chain 12 is illustrated by way of example. For the final modification of the illustrated polymer chain 12, alternatively or additionally, one or more coumarin groups may be provided as side groups of the polymer chain 12. Most concerted [2+2] cycloadditions are photochemically permissible electrocyclic reactions and are described by the Woodward-Hoffman rules. Stereochemistry can be predicted by these rules. This is a [π²σ+π²σ] cycloaddition, accompanied by the closure of a coplanar ring with orbitals. The reaction is initiated, for example, by irradiation with light of wavelength > 300 nm, where the exact wavelength can be varied by the derivatization of the coumarin groups. The polymer chains 12 are then linked via the coumarin groups acting as crosslinking agents, which correspondingly increases their molecular weight. The resulting viscoelastic polymer 10, or the entire OVD having viscoelastic polymer 10, should then be stored until use, for example in a brown glass vial or a completely opaque (heat-free) container, to reduce or preferably completely avoid exposure to light and thus avoid any risk of decay. After application to the patient's eye, the formed cyclobutane ring can then be photochemically cleaved, for example, with light at wavelengths < 300 nm. This causes polymer 10 to break down again into its shorter polymer chains 12, which can then be removed from the eye and degraded via natural drainage pathways. The absorption peak can also be customized here by using appropriate substituents, allowing cleavage to be performed at wavelengths up to 400 nm or greater. This is particularly important in cases where an OVD is retained behind an intraocular lens (IOL) during surgery, as the IOL may absorb in the UV or even partially in the visible light region (in the case of a yellow IOL).

[0036] As already mentioned, other chemical structures can also be used to create these reversible bonds between polymer chains 12 and produce viscoelastics with viscosities that can be changed and adjusted as needed. One class of these substances is cinnamate or cinnamic acid derivatives. In this regard, Figure 4 The [2+2] cycloaddition reaction of the cinnamic acid-substituted polymer chain 12 is shown. The general reaction principle corresponds to the general reaction principle of the coumarin group discussed above. However, for this purpose, a wide range of other photolytically cleavable chemical groups can also be selected and coupled and cleaved through the described mechanism. To covalently bind these functional groups to polymer chain 12, various reaction pathways known per se can be followed.

[0037] After the photodegradable viscoelastic polymer 10 has been produced, stabilizing compounds (e.g., free radical scavengers) can be added to the OVD, and the viscoelastic material can be packaged in suitable containers for storage and transport in the dark. In cases of subsequent surgical application, a distinction should be made between the desired activation time, the chemical degradation reaction time, and the drainage time. Since intraocular pressure typically peaks approximately 3–7 hours after surgery, guidelines for reaction time have been established to degrade polymer 10 as quickly as possible after use and significantly reduce its viscosity for drainage, preferably within minutes or at least within hours. Preferably, the reaction is completed, or at least generally completed, after 2–3 hours. As mentioned above, the activation time can be set to several seconds, depending on the chosen chemical structure. It can also take up to several hours, for example, when sunlight or ambient light is used to initiate the degradation reaction.

[0038] OVDs can, in principle, contain one or more therapeutic agents (e.g., antibiotics), which are also released into the capsule upon cleavage of polymer 10. One or more therapeutic agents can be intercalated into polymer 10 or covalently bonded to it. In the latter case, the covalent bond is preferably achieved using the same group 14 as the crosslinking group of polymer chain 12, such that the therapeutic agent is released with or via the same mechanism and triggering factors as the cleavage of polymer 10.

[0039] Figure 5 A schematic diagram of a repeating disaccharide unit of hyaluronic acid is shown, which can be used as a building block of polymer 10 or polymer chain 12. This D-glucuronic acid N-acetyl D-glucosamine disaccharide has a size of about 1 nm. Arrows Va-Vg are used to label various reactive functional groups and potential reaction sites for the derivatization of hyaluronic acid (HA). Va represents a carboxyl group, Vb represents a primary hydroxyl group, Vc represents a reduced end group of HA, Vd represents an N-acetyl group, and Ve, Vf, and Vg represent secondary hydroxyl groups. These groups Va-Vg can be used to attach functional group 14 or a crosslinking agent to the HA backbone in various ways. In addition to modifying hyaluronic acid for use in hydrogels that optionally release drugs, other chemical modifications for a wide range of applications are also known. Regarding the preferred end binding of functional groups, ring-opening reactions or coupling reactions using the reduced ends of hyaluronic acid are known. However, the inventive concept is not limited to hyaluronic acid; rather, other viscoelastic polymers 10 or their building blocks or polymer chains 12 can also be modified accordingly, leading to a wide range of different application scenarios and choices.

[0040] Figure 6A diagram of the lysis device 16 in a working example is shown. In this context, the lysis device 16 is integrated into an surgical microscope 18 (OPMI) and includes a light source 20, an optional light guide 22, and an optional camera (not shown). The viscoelastic polymer 10 can then be lysed by fully exposing the anterior chamber 24 of the eye 26 (left image), or by locally scanning along an illumination path around the cyst according to arrow VI, so as not to overexpose the retina (right image). Instead of light, the stimulus for lysis can also be a magnetic field or another energy source, optionally a geothermal energy source, to initiate lysis.

[0041] Alternatively or additionally, the pyrolysis device 16 can be designed to generate a magnetic field (not shown). This allows the pyrolysis of the polymer 10 in the OVD to be achieved by additionally loading the OVD with magnetic microspheres or nanospheres, which resonate with the magnetic field and thereby generate heat in the OVD (magnetic field-assisted degradation). The polymer 10 can then be thermally pyrolyzed. Alternatively, the generated heat can also be used to support photochemical pyrolysis.

[0042] Figure 7 A diagram of a lysis device 16 in another working example is shown. The lysis device 16 is typically designed to partially or completely cover the eye 26, for example, in the form of a contact lens, a pair of glasses, etc. The lysis device 16 enables a controlled, long-term treatment environment. The patient can wear the lysis device 16, optionally individually adapted, with an integrated light source 20 (e.g., a ring LED, several LEDs, etc.) to degrade the viscoelastic polymer 10 in the manner described above. The patient wears this lysis device 16, for example, during the recovery phase after surgery. Light of a predetermined wavelength for lysis is then delivered to the anterior chamber 24 of the eye 26, breaking the viscoelastic polymer 10 into its short polymer chains 12. This can be performed without the intervention of a surgeon. Furthermore, the lysis device 16 can be worn for the time required for substantial or complete degradation of the polymer 10.

[0043] The parameter values ​​specified in the literature for defining the specific characteristics of the subject matter of the invention, including the processes and measurement conditions, should also be considered to be covered within the scope of the invention in cases of deviations caused, for example, by measurement errors, systematic errors, DIN tolerances, etc.

[0044] List of reference numerals

[0045] 10 polymers

[0046] 12 polymer chains

[0047] 14 groups

[0048] 16 Pyrolysis Unit

[0049] 18 surgical microscopes

[0050] 20 light sources

[0051] 22 optical guides

[0052] 24 anterior chamber

[0053] 26 eyes

[0054] Va-Vg functional groups

[0055] VI exposure path.

Claims

1. An ophthalmic viscoelastic device comprising at least one viscoelastic polymer (10) capable of breaking down into lower molecular weight polymer chains (12). Its features are, The viscoelastic polymer (10) comprises at least two polymer chains (12) bonded to each other via at least one thermally and / or photochemically cleavable group (14).

2. The ophthalmic viscoelastic device as described in claim 1, Its features are, These polymer chains (12) have a molar mass between 70 kDa and 200 kDa, particularly between 76 kDa and 190 kDa, and / or the viscoelastic polymer (10) has an average molecular weight of at least 0.5 MDa, particularly at least 2.5 MDa.

3. The ophthalmic viscoelastic device as described in claim 1 or 2, Its features are, The at least one viscoelastic polymer (10) comprises at least one building unit from the group (14) of hyaluronic acid, alginate, chitosan, methylcellulose, hydroxypropyl methylcellulose, chondroitin sulfate, collagen and gelatin.

4. The ophthalmic viscoelastic device as described in any one of claims 1 to 3, Its features are, The at least one viscoelastic polymer (10) comprises polymer chains (12) bonded to each other end-to-end via the at least one thermally and / or photochemically cleavable group (14) and / or via side chain positions.

5. The ophthalmic viscoelastic device as described in any one of claims 1 to 4, Its features are, The ophthalmic viscoelastic device takes the form of a cohesive or dispersed ophthalmic viscoelastic device, and / or the concentration of the at least one viscoelastic polymer (10) based on the total volume of the ophthalmic viscoelastic device is between 0.1 mg / ml and 50 mg / ml, and / or the ophthalmic viscoelastic device contains at least one therapeutic agent, particularly an analgesic and / or antioxidant, wherein the therapeutic agent is preferably covalently bonded to the at least one viscoelastic polymer (10) and / or embedded in the viscoelastic polymer (10) via the at least one thermally and / or photochemically cleavable group (14).

6. The ophthalmic viscoelastic device as described in any one of claims 1 to 5, Its features are, This ophthalmic viscoelastic device contains stabilizers, particularly free radical scavengers, and / or magnetic particles, particularly micron and / or nanoparticles.

7. The ophthalmic viscoelastic device as described in any one of claims 1 to 6, Its features are, At least one thermally and / or photochemically cleavable group (14) is selected from compounds that can be cycloadded by [2+2] and / or chemically coupled by click.

8. The ophthalmic viscoelastic device as described in any one of claims 1 to 7, Its features are, The ophthalmic viscoelastic device should be stored in an insulated and / or opaque container.

9. A pyrolysis apparatus (16) comprising means for pyrolyzing at least one thermally and / or photochemically pyrolyzable group (14) of an ophthalmic viscoelastic device as claimed in any one of claims 1 to 8.

10. The pyrolysis apparatus (16) as described in claim 9. Its features are, The pyrolysis device includes a light source (20) for generating light with a wavelength that photochemically pyrolyzes the at least one group (14) as a means, and / or the pyrolysis device includes a magnetic device for generating a magnetic field as a means, through which the magnetic particles of the ophthalmic viscoelastic device can be heated to pyrolyze the at least one thermally and / or photochemically pyrolyzable group (14).

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