Patent Description:
The present disclosure relates to a hydrogel composition, and more particularly to a hydrogel composition and a hydrogel lens, which can load and slowly release active ingredients.

<CIT> discloses a composition for soft materials, which enables production of a soft material excellent in transparency, a stress relaxation property, and strength and having an elongation property that is not so much lowered even at high temperatures. This patent also aims to provide a soft material produced using the composition for soft materials of this patent. This patent relates to a composition for soft materials including polyrotaxane and a radical polymerizable monomer, the polyrotaxane including a cyclic molecule, a linear molecule threading through a cavity of the cyclic molecule in a skewered manner, and capping groups that cap both ends of the linear molecule, the polyrotaxane having at least one cyclic molecule with a radical polymerizable group, the polyrotaxane having at least two radical polymerizable groups.

<NPL>) discloses three kinds of novel hydrogels with excellent mechanical performance that have been developed, based on different concepts. Two of them exhibit high resistance to extension, up to <NUM>-<NUM> times the original length, by introducing special cross-linking structures. The third has a high modulus (sub-megapascal), with a failure compressive stress as high as <NUM> MPa, through a double network structure. In this article, the structural and mechanical features of these gels and the status of current studies have been described.

<CIT> discloses an aquagel with high intensity, a preparation method and the function thereof. The method comprises the following steps of: <NUM>) preparing an aqueous surfactant solution with certain concentration and conducting irradiation and overoxidation under the condition of oxygen entrance; <NUM>) mixing the aqueous surfactant solution obtained from step <NUM>) with monomers and distilled water according to a certain volume ratio, inletting nitrogen to deoxidize, and sealing the container to form a reaction system; and <NUM>) putting the sealed reaction system under <NUM>-<NUM> DEG C to react for <NUM>-<NUM> hours to obtain the aquagel with high mechanical intensity. The aquagel is optically transparent and has high mechanical intensity, and the softness and hardness of which can be conveniently adjusted by controlling the preparation process, so as to meet the needs of different application occasions. The aquagel can be applied to biological, medical, optical devices and the like fields. The method of this patent is realized by low-temperature and normal-pressure operation, low dosage, low energy consumption, high production efficiency, simple process and low cost.

In the past decades, delivery of ophthalmic drugs (or active ingredients) has been an important challenge for ophthalmologists, and topical eye drops were commonly used to treat human eyes. However, in this way of drug delivery, the drug is instantly diluted instantly after being dropped into an eye of a human body, and can easily be discharged from a tear orifice of the eye. A retention time of the drug in the eye of the human body is short, which results in a poor therapeutic effect. Therefore, ophthalmologists may need to consider increasing a usage frequency or a dosage of the drug, but such measures may also increase risks of side effects from the drug. Therefore, the above-mentioned drug delivery method still has room for improvement.

In response to the above-referenced technical inadequacies, the present disclosure provides a hydrogel composition and a hydrogel lens according to independent claims <NUM> and <NUM>. The dependent claims show further embodiment of claims <NUM> and <NUM>.

In one aspect, the present disclosure provides a hydrogel composition which includes a hydrophilic monomer, a cross-linker, an initiator and a rotaxane compound. Based on a total weight of the hydrogel composition, a content range of the hydrophilic monomer is between <NUM> wt% and <NUM> wt%, a content range of the cross-linker is between <NUM> wt% and <NUM> wt%, a content range of the initiator is between <NUM> wt% and <NUM> wt%, and a content range of the rotaxane compound is between <NUM> wt% and <NUM> wt%. The rotaxane compound includes at least one cyclic molecule and at least one linear molecule passing through the at least one cyclic molecule in a string manner, and a weight ratio of the rotaxane compound relative to the hydrophilic monomer is between <NUM>:<NUM> and <NUM>:<NUM>. In the rotaxane compound, a number average molecular weight of the linear molecule is between <NUM>,<NUM> and <NUM>,<NUM>, and the rotaxane compound does not include any slopper or capping used for preventing the cyclic molecule from detaching from two ends of the linear molecule.

In another aspect, the present disclosure provides a hydrogel lens which includes a lens body that is formed by the above-mentioned hydrogel composition.

Therefore, by virtue of "introduction of a rotaxane compound into a hydrogel composition", the hydrogel composition and the hydrogel lens of the present disclosure can have effects of loading and slowly releasing active ingredients.

It is worth mentioning that, although the rotaxane compound is introduced into the hydrogel lens, the hydrogel lens of the present disclosure can not only have the effects of loading and slowly releasing the active ingredients, but also maintain required characteristics of the hydrogel lens, such as a lens base curve (BC), a lens center thickness (CT), a lens diameter (DIA), a refractive index, a visible light transmittance, and a dynamic contact angle.

According to the technical inadequacies mentioned in the background of the present disclosure, in the past decades, delivery of ophthalmic drugs (or active ingredients) has been an important challenge for ophthalmologists, and topical eye drops were commonly used to treat human eyes. However, in this way of drug delivery, the drug is instantly diluted instantly after being dropped into an eye of a human body, and can easily be discharged from a tear orifice of the eye. A retention time of the drug in the eye of the human body is short, which results in a poor therapeutic effect. Therefore, ophthalmologists may need to consider increasing a usage frequency or a dosage of the drug, but such measures may also increase risks of side effects from the drug. Therefore, the above-mentioned drug delivery method still has room for improvement.

To improve the technical inadequacies mentioned above, an object of the present disclosure is to provide a new type of hydrogel lens (i.e., hydrogel contact lens), which is a strategy for transportation of active ingredients. That is, the present disclosure provides a new delivery mode of the active ingredients by using the new type of hydrogel lens, which can load and slowly release the active ingredients. The technology of the present disclosure can maintain the active ingredients on the hydrogel contact lens to prolong a retention time of the active ingredients on the human eyes, and improve a utilization efficiency of the active ingredients, thereby improving wearing comfort for a user, and even achieving a long-term maintenance effect.

To achieve the above object, an embodiment of the present disclosure provides a hydrogel composition for preparing a hydrogel lens. The hydrogel composition includes a hydrophilic monomer, a cross-linker, an initiator, and a rotaxane compound.

Based on a total weight of the hydrogel composition being <NUM> wt%, a content range of the hydrophilic monomer in the hydrogel composition is between <NUM> wt% and <NUM> wt%, and preferably between <NUM> wt% and <NUM> wt%. A content range of the cross-linker in the hydrogel composition is between <NUM> wt% and <NUM> wt%, and preferably between <NUM> wt% and <NUM> wt%. A content range of the initiator in the hydrogel composition is between <NUM> wt% and <NUM> wt%, and preferably between <NUM> wt% and <NUM> wt%. In addition, a content range of the rotaxane compound in the hydrogel composition is between <NUM> wt% and <NUM> wt%, preferably between <NUM> wt% and <NUM> wt%, and more preferably between <NUM> wt% and <NUM> wt%.

To enable the rotaxane compound to be uniformly dispersed in the hydrogel composition and to exert an expected effect, a weight ratio of the rotaxane compound relative to the hydrophilic monomer is between <NUM>:<NUM> and <NUM>:<NUM>, preferably between <NUM>:<NUM> and <NUM>:<NUM>, and more preferably between <NUM>:<NUM> and <NUM>:<NUM>.

If the weight ratio of the rotaxane compound relative to the hydrophilic monomer is less than a lower limit of the above-mentioned ratio range (i.e., <NUM>:<NUM>), the rotaxane compound may not be uniformly dispersed in the hydrogel composition due to a high addition amount of the rotaxane compound, so that a finally formed hydrogel contact lens may have poor quality, such as poor refractive index or poor light transmittance.

On the contrary, if the weight ratio of the rotaxane compound relative to the hydrophilic monomer is greater than an upper limit of the above-mentioned ratio range (i.e., <NUM>:<NUM>), the rotaxane compound may not be able to exert the expected effect in the finally formed hydrogel contact lens (i.e., effectively loading and slowly releasing the active ingredients) due to a low addition amount of the rotaxane compound.

Material types of each component in the hydrogel composition according to the embodiment of the present disclosure will be described in the following paragraphs.

The hydrophilic monomer preferably has a vinyl group, an acetyl group, a propenyl group, or an acryl group in its molecular structure.

In various embodiments of the present disclosure, the hydrophilic monomer is at least one material selected from a group consisting of N-vinyl pyrrolidone (NVP), <NUM>-hydroxyethyl methacrylate (HEMA), methacrylic acid (MAA), methyl methacrylate (MMA), acrylic acid (AAc), N,N-dimethyl acrylamide (DMA), <NUM>,<NUM>-dihydroxypropyl methacrylate (GMMA), N,N-dimethyl methacrylamide, and N-vinyl-N-methyl acetamide.

In various embodiments of the present disclosure, the hydrogel composition further includes a silicone compound, and the silicone compound is at least one material selected from a group consisting of silicon monomer, silicon-based polymer (i.e., siloxane), and silicon pre-polymer. Accordingly, the finally formed hydrogel contact lens can be a silicone hydrogel contact lens, but the present disclosure is not limited thereto.

In various embodiments of the present disclosure, the cross-linker is at least one material selected from a group consisting of ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, allyl methacrylate, triethylene glycol dially ether, tetraethylene glycol dially ether, and <NUM>,<NUM>,<NUM>-trimethylolpropane trimethacrylate.

In various embodiments of the present disclosure, the initiator is a photo-initiator, and a content range of the photo-initiator in the hydrogel composition is between <NUM> wt% and <NUM> wt%.

The photo-initiator is at least one material selected from a group consisting of bis(<NUM>,<NUM>-difluoro-<NUM>-(<NUM>-hydropyrro-<NUM>-yl)- phenyl)titanocene, phenyl-bis-(<NUM>,<NUM>,<NUM>-trimethylbenzoyl)-phosphine oxide, and <NUM>-hydroxy-<NUM>-methyl-<NUM>-phenyl-<NUM>-porpanone.

Furthermore, the rotaxane compound includes at least one cyclic molecule and at least one linear molecule, and the at least one linear molecule passes through the at least one cyclic molecule in a string manner.

To enable the rotaxane compound to effectively load and slowly release active ingredients, a weight ratio of the cyclic molecule relative to the linear molecule has a specific range. For example, the weight ratio of the at least one cyclic molecule relative to the at least one linear molecule is preferably between <NUM>:<NUM> and <NUM>:<NUM>, and more preferably between <NUM>:<NUM> and <NUM>:<NUM>.

That is, in the rotaxane compound, a quantity of the at least one cyclic molecule is generally plural, a quantity of the linear molecule is generally one, and the at least one linear molecule passes through a plurality of cyclic molecules.

Accordingly, a sufficient space can be formed between the plurality of cyclic molecules and the linear molecule to load an effective amount of active ingredients. Furthermore, a dynamic structure can be formed between the plurality of cyclic molecules and the linear molecule, so that the rotaxane compound can achieve an effect of slowly releasing the active ingredient.

If the weight ratio of the cyclic molecule relative to the linear molecule exceeds the above ratio range, the effect of the rotaxane compound on loading and slowly releasing the active ingredients may become unsatisfactory.

In terms of material types, the cyclic molecule may be, for example, cyclodextrin or a derivative thereof, but the present disclosure is not limited thereto.

In various embodiments of the present disclosure, the cyclodextrin is at least one material selected from a group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, (<NUM>-hydroxypropyl)-γ-cyclodextrin, sulfobutylether-β-cyclodextrin, and methyl-β-cyclodextrin.

In addition, the cyclic molecule may also be, for example, crown ether or a derivative thereof.

In various embodiments of the present disclosure, the crown ether is at least one material selected from a group consisting of <NUM>-crown-<NUM>, <NUM>-crown-<NUM>, <NUM>-crown-<NUM>, benzo-<NUM>-crown-<NUM>, benzo-<NUM>-crown-<NUM>, dicyclohexyl-<NUM>-crown-<NUM>, <NUM>-(hydroxymethyl)-<NUM>-crown-<NUM>-ether, <NUM>-(hydroxymethyl)-<NUM>-crown-<NUM>-ether, and <NUM>-(hydroxymethyl)-<NUM>-crown-<NUM>-ether.

Furthermore, the linear molecule is at least one material selected from a group consisting of polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polypropylene glycol (PPG).

The polyethylene glycol has a chemical structure of formula (<NUM>):
<CHM>.

The polyvinyl alcohol has a chemical structure of formula (<NUM>):
<CHM>.

The polypropylene glycol has a chemical structure of formula (<NUM>):
<CHM>.

In addition, "n" is preferably a positive integer greater than <NUM>, and more preferably a positive integer between <NUM> and <NUM>,<NUM>. Furthermore, a number average molecular weight of the linear molecule is preferably between <NUM> and <NUM>,<NUM>, but the present disclosure is not limited thereto.

It is worth mentioning that an object of the present disclosure is to introduce the "rotaxane compound" into the hydrogel composition that is used to prepare the hydrogel lens, so that the hydrogel lens can be cooperated with an inclusion technology and have the effect of loading and slowly releasing the active ingredient by the rotaxane compound.

The above-mentioned "inclusion technology" is to embed the active ingredient (also called target substance) into the cyclic molecule, so that the active ingredient can be in a stable state. Furthermore, the cyclic molecule can be combined with the linear molecule to form the rotaxane compound, thereby achieving the purpose of slowly releasing the active ingredient.

On the other hand, the "inclusion technology" refers to a technology in which one molecule is embedded into a cavity structure of another molecule to form an inclusion compound. Among them, the inclusion compound is composed of a host molecule and a guest molecule. In addition, the host molecule has a relatively large cavity structure, which is sufficient to contain the guest molecule to form a molecular capsule.

In a specific embodiment of the present disclosure, the cyclic molecule of the rotaxane compound is cyclodextrin, and the linear molecule of the rotaxane compound is polyethylene glycol (PEG), but the present disclosure is not limited thereto.

Further, a molecular structure of the cyclodextrin has a tire-like shape. A secondary hydroxyl group on C-<NUM> and C-<NUM> atoms of each glucose residue is located at one end of the cyclodextrin and has a slightly larger diameter. A primary hydroxyl group on C-<NUM> atom of each glucose residue is located at another end of the cyclodextrin and has a slightly smaller diameter. Therefore, an inside of the cyclodextrin is a hydrophobic cavity structure, which can provide a fat-soluble active ingredient, such as menthol or vitamin E acetate, to enter and to be loaded therein.

The following chemical structures are chemical structures of three main types of cyclodextrins.

When a cyclodextrin and a fat-soluble active ingredient are dissolved in a solvent, the fat-soluble active ingredient usually enters a hydrophobic cavity structure of the cyclodextrin, a peripheral hydroxyl group (-OH group) of the cyclodextrin will interact with an aqueous solution or a highly-polar solution (i.e., hydrophilic monomer or contact lens care solution) to increase a solubility of the fat-soluble active ingredient.

In addition to forming a complex of the cyclodextrin and the fat-soluble active ingredient to increase the solubility of the fat-soluble active ingredient, the complex can be combined with a linear molecule (i.e., PEG) to form a rotaxane compound, thereby facilitating stable release of the loaded active ingredient.

More specifically, the above-mentioned rotaxane compound is formed by a supramolecular force between the cyclic molecule and the linear molecule. The rotaxane compound includes one or several cyclic molecules (wheel structures) and one linear molecule (shaft structure). The linear molecule and the cyclic molecules are connected by a weak interaction, such as mechanical bonds, instead of strong covalent bonds or coordination bonds. Therefore, this supramolecular polymer has less stability and a dynamic structure, which is suitable for loading an active ingredient, such as a small molecule drug, a protein drug, or a gene.

It is worth mentioning that for the present application, extensive research has been conducted on academic literature regarding the ability of the rotaxane compound to load active ingredients.

For example, the literature of<NPL> pointed out that cyclodextrin can effectively load menthol; the literature of<NPL> pointed out that hydroxypropyl-β-cyclodextrin (HP-β-CD) can effectively load vitamin B12. In addition, the literature of <NPL> also pointed out that hydroxypropyl-β-cyclodextrin (HP-β-CD) can effectively load vitamin E, which can further increase the solubility of the vitamin E in water.

It is also worth mentioning that, as mentioned above, the weight ratio of the rotaxane compound relative to the hydrophilic monomer is usually between <NUM>:<NUM> and <NUM>:<NUM>. In some specific embodiments of the present disclosure, a molecular structure of the hydrophilic monomer preferably has an acryl group, and in these specific embodiments, the weight ratio of the rotaxane compound relative to the hydrophilic monomer is preferably between <NUM>:<NUM> and <NUM>:<NUM>.

The functional group having the acryl group may be, for example, at least one of the following four chemical structures.

Furthermore, it has been found that a preferred range of the weight ratio of the rotaxane compound relative to the hydrophilic monomer is different under different material selection of cyclodextrin.

For example, when the cyclic molecule in the rotaxane compound is α-cyclodextrin or β-cyclodextrin, the weight ratio of the rotaxane compound relative to the hydrophilic monomer is preferably between <NUM>:<NUM> and <NUM>:<NUM>. When the cyclic molecule in the rotaxane compound is hydroxypropyl-β-cyclodextrin, the weight ratio of the rotaxane compound relative to the hydrophilic monomer is preferably between <NUM>:<NUM> and <NUM>:<NUM>. In addition, when the cyclic molecule in the rotaxane compound is (<NUM>-hydroxypropyl)-γ-cyclodextrin, the weight ratio of the rotaxane compound relative to the hydrophilic monomer is preferably between <NUM>: <NUM> and <NUM>:<NUM>.

To increase a ultraviolet light blocking ability of the hydrogel lens, in various embodiments of the present disclosure, the hydrogel composition further includes an ultraviolet light blocking monomer, and a content range of the ultraviolet light blocking monomer in the hydrogel composition is between <NUM> wt% and <NUM> wt%.

The ultraviolet light blocking monomer is at least one material selected from a group consisting of benzophenone and benzotriazole.

To increase a solubility of the hydrogel composition, in various embodiments of the present disclosure, the hydrogel composition further includes a co-solvent, and a content range of the co-solvent in the hydrogel composition is between <NUM> wt% and <NUM> wt%.

The co-solvent is at least one material selected from a group consisting of glycerol, isopropyl alcohol, n-butanol, t-butanol, t-amyl alcohol, and n-hexanol.

To enable the hydrogel lens to have a specific color, in various embodiments of the present disclosure, the hydrogel composition further includes a dye, and a content range of the dye in the hydrogel composition is between <NUM> wt% and <NUM> wt%.

The dye is at least one material selected from a group consisting of reactive blue <NUM> (disodium <NUM>-amino-<NUM>,<NUM>-dioxo-<NUM>-[<NUM>-(<NUM>-sulfonato oxyethyl sulfonyl) anilino] anthracene-<NUM>-sulfonate), Sudan III (<NUM>-[<NUM>-(phenylazo) phenylazo]-<NUM>-naphthol, Indigo (<NUM>,<NUM>'-bis(<NUM>,<NUM>-dihydro- <NUM>-oxoindolyl idene)), and Quinoline Yellow (disodium <NUM>-(<NUM>,<NUM>-dioxo- <NUM>,<NUM>-dihydro-<NUM>-inden-<NUM>-yl) quinolone-<NUM>,<NUM>-disulfonate).

Furthermore, the linear molecule (i.e., PEG, PVA, PPG) in the rotaxane compound has a relatively high molecular weight, and thus has a relatively long polymer chain. More specifically, the linear molecule in the rotaxane compound has a number average molecular weight between <NUM>,<NUM> and <NUM>,<NUM>, preferably between <NUM>,<NUM> and <NUM>,<NUM>, and more preferably between <NUM>,<NUM> and <NUM>,<NUM>. According to the above configuration, since the linear molecule in the rotaxane compound has a sufficiently long polymer chain, the cyclic molecule has enough space to slide on the linear molecule, so that the cyclic molecule is not easily detached from the linear molecule. Accordingly, the rotaxane compound does not need to include any slopper or capping that is used to prevent the cyclic molecule from detaching from two ends of the linear molecule. In other words, in the rotaxane compound, the two ends of the linear molecule may not need to be formed with the slopper or capping, which can still stably maintain the shape of the rotaxane compound.

Furthermore, in the rotaxane compound, an outer periphery of the cyclic molecule (i.e., cyclodextrin) has a hydrophilic functional group (i.e., hydroxyl group, -OH group), so that the outer periphery of the cyclic molecule has a higher hydrophilicity. Furthermore, an inner side of the cyclic molecule has a hydrophobic cavity structure, so that the inner side of the cyclic molecule has a higher hydrophobicity, and the hydrophobic cavity structure can be used to provide fat-soluble active ingredients to enter therein, thereby enhancing a loading effect of the active ingredients. Since the outer periphery of the cyclic molecule has the hydrophilic functional group, the rotaxane compound can interact with the hydrophilic monomer in the hydrogel composition (i.e., NVP, HEMA) through the hydrophilic functional group on the outer periphery of the cyclic molecule. Accordingly, the rotaxane compound can be uniformly dispersed in the hydrogel composition based on the interaction between polar molecules (cyclic molecule and hydrophilic monomer).

More specifically, as shown in <FIG>, in the hydrogel composition <NUM>, the linear molecule <NUM> of the rotaxane compound <NUM> is dispersed in the hydrophilic monomer <NUM> in a tortuous form. In addition, the rotaxane compound <NUM> further includes a plurality of cyclic molecules <NUM>, and the plurality of cyclic molecules <NUM> are threaded onto the linear molecule <NUM> in a series connection.

It is worth mentioning that, in the hydrogel composition <NUM>, the plurality of series-connected cyclic molecules <NUM> and the adjacent plurality of series-connected cyclic molecules <NUM> are capable of being attracted to each other by a hydrogen bonding force and arranged in a stacking manner (as shown in <FIG>).

In addition, referring to <FIG> again, in the hydrogel composition <NUM>, parts of the cyclic molecules <NUM> are not threaded onto the linear molecule <NUM>, but scattered on an outside of the linear molecule <NUM>, which exist as independent molecules, but the present disclosure is not limited thereto.

Further, as shown in <FIG>, based on the hydrogen bonding force, the plurality of series-connected cyclic molecules <NUM> on the linear molecule <NUM> are arranged in a manner of heads to heads and tails to tails.

In addition, it is worth mentioning that, the hydrogel composition <NUM> can have a relatively excellent tensile property through the addition of the rotaxane compound <NUM>. Specifically, the hydrogel lens made from the hydrogel composition <NUM> has an elongation between <NUM>% and <NUM>%, and more preferably between <NUM>% and <NUM>%.

The method for preparing the rotaxane compound may include, for example, adding the cyclic molecule and the linear molecule into water with the weight ratio described in the above-mentioned embodiment; mixing and stirring for several hours until the reaction is completed to obtain a reaction solution; and then drying the reaction solution to obtain a rotaxane compound powder.

The method for preparing the hydrogel composition may include, for example, slowly adding the rotaxane compound powder, a cross-linker, and an initiator to a hydrophilic monomer, and mixing and stirring for several hours until the reaction is completed to obtain the hydrogel composition. That is, in this embodiment, the cyclic molecule and the linear molecule are formed into the rotaxane compound before preparing the hydrogel composition.

In addition, the method for preparing the hydrogel composition can also include, for example, slowly adding the cyclic molecule, the linear molecule, the cross-linker, the initiator and other materials to the hydrophilic monomer, and mixing and stirring for several hours until the reaction is completed to obtain the hydrogel composition. In other words, in this embodiment, the cyclic molecule and the linear molecule are formed into the rotaxane compound while preparing the hydrogel composition.

The method for preparing the hydrogel lens may include, for example, injecting the above hydrogel composition into a mold for preparing the hydrogel lens; and performing a curing molding process on the hydrogel composition to form a semi-finished dry film product of the hydrogel lens.

The method further includes immersing the semi-finished dry film product of the hydrogel lens in a buffer solution until the hydrogel lens swells (i.e., hydration process); filling the buffer solution in a packaging container; immersing the hydrogel lens in the buffer solution; and then sealing and sterilizing the hydrogel lens, thus completing the production of the hydrogel contact lens product.

The above-mentioned active ingredient (i.e., the small molecule drug, the protein drug or the gene) can be added or mixed into the material used to prepare the contact lens; or, for example, the active ingredient can be loaded onto the contact lens during demolding and swelling; or, for example, the active ingredient can be dissolved in the buffer solution for soaking the contact lens and then loaded on the contact lens. Accordingly, when a user attaches the contact lens to his eye, the active ingredient can be slowly released from the contact lens over time and be absorbed by his eye.

In other words, the method for adding or loading the active ingredient (i.e., the small molecule drug, the protein drug or the gene) into the rotaxane compound may include: adding the active ingredient during the preparation of the lens material, adding the active ingredient during the hydration of the lens, or adding the active ingredient in the buffer solution.

Under this slow-release system, the active ingredient that can be loaded onto the contact lens may be, for example, an ingredient with cooling or anti-itching effects, such as menthol, l-menthol, camphor, d-camphor, dl-camphor, borneol, d-borneol, or potassium chloride.

The active ingredient may also be, for example, an ingredient with an antiinflammatory effect, such as: lysozyme hydrochloride, dipotassium glycyrrhizinate, <NUM>-aminocaproic acid, ε-aminocaproic acid, <NUM>-aminohexanoic acid acid, zinc sulfate, vitamin B2, sodium azulene sulfonic acid, sulfamethoxazole, sulfamethoxazole sodium, or prano-profen.

The active ingredient may also be, for example, an ingredient with an effect of relieving symptoms of conjunctival hyperemia, such as naphazoline, naphazoline hydrochloride, tetrahydrozoline, tetryzoline, tetrahydrozoline hydrochloride, chlorobutanol, chlorobutanol hemihydrate, phenylephrine hydrochloride, or phenylephrine.

The active ingredient may also be, for example, an ingredient with antioxidation or eye fatigue effects, such as vitamin E, α-tocopheryl acetate, L-potassium aspartate, magnesium L-aspartate, chondroitin sulfate, chondroitin sulfate sodium salt, sodium chondroitin chloride, neostigmine methyl-sulfate, arginine, vitamin B12, cyanocobalamin, methyl-cobalamin, adeno-sylcobalamin, hydroxo-cobalamin, vitamin B5, pantothenic acid, vitamin B6, pyridoxine hydrochloride, vitamin A, vitamin A palmitate, or taurine.

The active ingredient may also be, for example, an ingredient with anti-allergic or anti-itch effects, such as diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine, chlorpheniramine maleate, or tranilast.

In addition, the active ingredient may also be, for example, an ingredient with moisturizing or soothing effects, such as boric acid, glycerine, hyaluronic acid, polyol, or allantoin.

The embodiment of the present disclosure also provides a hydrogel lens (hydrogel contact lens) including a lens body that is formed by the above hydrogel composition.

The rotaxane compound is distributed on at least one surface of a concave arc surface or a convex arc surface of the lens body to form a rotaxane layer, and the rotaxane compound is configured to carry an active ingredient. The active ingredient is at least one of the small molecule drug, the protein drug, and the gene.

Accordingly, when a user attaches the contact lens (hydrogel lens) to his eye, the active ingredient can be slowly released from the contact lens over time and be absorbed by his eye.

In addition, a refractive index of the lens body is preferably between <NUM> and <NUM>, and more preferably between <NUM> and <NUM>.

A visible light transmittance of the lens body is preferably not less than <NUM>%, and more preferably not less than <NUM>%.

A dynamic contact angle (DCA) of the lens body is preferably less than <NUM>, and more preferably less than <NUM>, thereby having good wettability.

In various embodiments of the present disclosure, the lens body of the contact lens may also be, for example, any lens body known in the technical field. For example, the lens body may be, for example, a rigid gas permeable (RGP) contact lens, a hydrogel soft contact lens (SCL), or a silicone hydrogel soft contact lens.

Hereinafter, the content of the present disclosure will be described in detail with reference to Exemplary Examples <NUM> to <NUM> in Table <NUM>. However, the following examples are only used to help understand the present disclosure, and the scope of the present disclosure is not limited to these examples.

The hydrogel lenses of the Exemplary Examples shown in Table <NUM> are obtained by the above preparation method of the hydrogel composition and the preparation method of the hydrogel lens.

After the preparations of the exemplary lenses in Table <NUM> are completed, physical and chemical properties are tested, such as: a base curve (BC), a center thickness (CT), a diameter (DIA), a refractive index, a light transmittance, a water content, an atmospheric dehydration rate, a lubricity, a dynamic contact angle (DCA), an elongation, a water extraction test, and a hexane extraction test.

The dynamic contact angle (DCA) is measured by using a dynamic contact angle measuring instrument, and a captive bubble method is used as the method to measure the dynamic contact angle. The captive bubble method is a measurement method often used to measure the wettability or hydrophilicity of contact lenses. Generally, the dynamic contact angle of a contact lens can be less than <NUM> degrees. According to the following examples <NUM> to <NUM>, the dynamic contact angles of the hydrogel contact lenses are not more than <NUM> degrees, specifically not more than <NUM> degrees, and more specifically not more than <NUM> degrees. That is, the hydrogel contact lenses in the examples <NUM> to <NUM> all have good wettability.

The atmospheric dehydration rate is one of the important indicators that can be used to evaluate a water retention level of a lens material. The measurement method of the atmospheric dehydration rate is to: place a hydrated and swelled hydrogel lens on a damp cloth and gently wipe the hydrogel lens to remove excess water; put the hydrogel lens on a sample pan of a scale; weigh and record a weight of the hydrogel lens; and record the weight of the hydrogel lens at different time points, such as the <NUM>th minute of atmospheric dehydration, the <NUM>th minute of atmospheric dehydration, the <NUM>th minute of atmospheric dehydration. Table <NUM> shows the measurement results of the atmospheric dehydration rates of the lenses in different exemplary examples.

According to market research, rapid loss of moisture in contact lens is one of the main reasons why users consider on not using contact lens. As shown in Table <NUM> below, the inventor of the present application surprisingly found that, compared with the hydrogel lens without adding rotaxane compound (Comparative Example <NUM>), the hydrogel lens added with rotaxane compound (Exemplary Examples <NUM> to <NUM>) has a lower dehydration rate. In other words, the drying rate of the contact lens added with rotaxane compound is relatively slow, and the user is less likely to feel the rapid loss of moisture in the contact lens.

The measurement of elongation is used to evaluate a stretch elasticity of a lens body of a contact lens. The measurement method of elongation is using a ruler to measure the lens body after hydration and swelling. More specifically, the measurement method is fixing two ends of the lens body along its central axis at a relative distance of <NUM> (i.e., visible length of the lens body is <NUM>), in which a left fixed end of the lens body is aligned with the ruler; stretching the lens body toward a right side of the lens body along the direction of its central axis with a fixed force; and recording the final length (cm) of the lens body before the lens body is ruptured. The calculating of the elongation is: subtracting the length value before stretching from the length value after stretching, and then dividing by the length value before stretching to obtain an elongation value, which is expressed as a percentage.

The calculation formula of elongation is: <MAT>.

The measurement of elongation is one of the important indicators for evaluating the property of a contact lens. If the contact lens is too hard (i.e., the elongation thereof is less than <NUM>%), the contact lens will easily cause a user to feel uncomfortable when the user wears the contact lens on his eye. If the contact lens is too soft (i.e., the elongation thereof is greater than <NUM>%), it would be difficult for users preparing to wear the contact lens to place the contact lens flatly on their fingertips. The hydrogel lenses made according to the following Exemplary Examples <NUM> to <NUM> have elongations between <NUM>% and <NUM>%, and more specifically between <NUM>% and <NUM>%.

The measurement of lubricity is one of the important indicators for evaluating the wearing comfort of a contact lens. The contact lens with good lubricity can provide a user with good wearing comfort. The evaluation method of the lubricity is to use a blind test. The score of the blind test is <NUM> point to <NUM> points. The higher the score is, the better the lubricity is. According to the following Exemplary Examples <NUM> to <NUM>, the hydrogel lenses all have a score of about <NUM> points.

The measurement of water content refers to the amount of water absorbed by a lens body of a contact lens under equilibrium. The water content is determined according to ISO18369-<NUM>. The water content can be measured by: taking the lens body after hydration and swelling; placing the lens body on a damp cloth and gently wiping the lens body to remove excess water; putting the lens body in a sample pan on a scale, and weighing and recording the weight (a) of the lens body before dehydration; and then putting the lens body in an oven with a constant temperature and a constant humidity for several hours, and weighing and recording the weight (b) of the lens body after dehydration. The water content is calculated by subtracting the weight (b) of the lens body after dehydration from the weight (a) of the lens body before dehydration, and then dividing by the weight (a) of the lens body before dehydration to obtain a calculated value. The calculated value is the water content of the lens body. The water content can be expressed as a percentage. The hydrogel lenses made according to the following Exemplary Examples <NUM> to <NUM> all have the water content between <NUM>% and <NUM>% (w/w), specifically between <NUM>% and <NUM>% (w/w), and more specifically between <NUM>% and <NUM> %.

The calculation formula for water content is: <MAT>.

It should be noted that, in the following Table <NUM>, the base curve (BC) and the diameter (DIA) of the lens body are measured by a contact lens optical measuring instrument. The central thickness (CT) of the lens body is measured by a lens thickness detector. The refractive index of the lens body is measured by an Abbe refraction-meter. The light transmittance of the lens body is obtained by measuring the visible light transmittance value using an ultraviolet spectrometer.

The following Table <NUM> lists the hydrogel compositions of Comparative Example <NUM> (control group) and Exemplary Examples <NUM> to <NUM>, and Table <NUM> also shows the test results of the physical and chemical properties of the hydrogel lenses. The above Exemplary Examples are merely illustrative and are not intended to limit the scope of the present disclosure.

Specifically, the hydrogel compositions of Comparative Example <NUM> and Exemplary Examples <NUM> to <NUM> all include: <NUM> wt% of hydrophilic monomer, <NUM> wt% of cross-linker, <NUM> wt% of initiator, <NUM> wt% of UV blocking monomer, <NUM> wt% of co-solvent, and <NUM> wt% of dye. Among them, Comparative Example <NUM> is a control group, which does not contain rotaxane compound, while the Exemplary Examples <NUM> to <NUM> are added with different weight ratio of rotaxane compound. In the rotaxane compounds of Exemplary Examples <NUM> to <NUM>, cyclodextrin is used as the cyclic molecule, and polyethylene glycol (PEG) is used as the linear molecule.

As shown in Table <NUM>, compared to the hydrogel lens without rotaxane compound (Comparative Example <NUM>, control group), the hydrogel lenses added with rotaxane compound (Exemplary Example <NUM> to Exemplary Example <NUM>) have lower dynamic contact angles. In other words, the contact lenses added with rotaxane compound have better wettability.

As shown in Table <NUM>, compared to the hydrogel lens without rotaxane compound (Comparative Example <NUM>, control group), the hydrogel lenses added with rotaxane compound (Exemplary Example <NUM> to Exemplary Example <NUM>) have lower atmospheric dehydration rates. In other words, the drying rates of the hydrogel lenses added with rotaxane compound are relatively slow, so that the user (wearer) is less likely to feel dryness from the lenses.

As shown in Table <NUM>, the performances of the basic physical and chemical properties (i.e., the base curve, the center thickness, the diameter, the refractive index, the elongation, the transmittance, the lubricity) of the hydrogel lenses added with rotaxane compound (Exemplary Example <NUM> to Exemplary Example <NUM>) are not inferior to that of the hydrogel lens without rotaxane compound (Comparative Example <NUM>, control group). That is, since the rotaxane compound is introduced into the hydrogel lens, the hydrogel lens not only has better wettability, lower atmospheric dehydration rate, potential for loading and slowly releasing active ingredients, but also can maintain the characteristics for contact lens requirements.

Furthermore, the water extraction rate (%) and the hexane extraction rate (%) of the hydrogel lenses in Table <NUM> are relatively low, which shows that the curing of the hydrogel compositions is quite complete.

Two methods of clinical evaluation of wearing status of contact lens commonly used in practical operation are introduced as follows, which include questionnaire interviews and tear meniscus height.

Questionnaire interview (subjective test) is to use contact lens questionnaire to ask about the symptoms of wearing, the frequency of occurrence, and the feeling of wearing for a long time to understand the actual condition of the wearer.

The evaluation method of the questionnaire interview is to immerse the hydrogel lenses made of Comparative Example <NUM> and Exemplary Examples <NUM> to <NUM> of Table <NUM> in a contact lens preservation solution containing menthol, thereby loading the menthol on the hydrogel lenses; and then take out the hydrogel lenses. Next, five subjects for a comprehensive evaluation test are selected. The test was completed by the five subjects aged between <NUM> and <NUM> years old. All the five subjects performed the test without knowing the composition ratio of the hydrogel lenses and the added ingredients of the drug. The score is on a scale from <NUM> to <NUM> points. The higher the score is, the stronger the feedback provided by the subjects of the test item is. The comprehensive evaluation test results of the five subjects are shown in Table <NUM>.

Tear meniscus height is observed by using a corneal topography system, and the height of the tear river is measured by observing the tear layer to determine whether a subject's tears are sufficient. The height of a normal person's tear channel is about <NUM>. If the measured height is lower than <NUM>, the test result means that there is insufficient tear secretion.

The evaluation method of the tear meniscus height is to immerse the hydrogel lenses made of Comparative Example <NUM> and Exemplary Examples <NUM> to <NUM> of Table <NUM> in a contact lens preservation solution containing menthol, thereby loading the menthol on the hydrogel lenses; and then take out the hydrogel lenses. Next, five subjects were selected, and the tear meniscus height was measured to determine the amount of tear secretion of the subjects. When the menthol continues to remain active, the menthol stimulates the secretion of tears. The test was completed by the five subjects aged between <NUM> and <NUM> years old. All the five subjects performed the test without knowing the composition ratio of the hydrogel lenses and the added ingredients of the drug. The comprehensive evaluation test results of the five subjects are shown in Table <NUM>.

In conclusion, by virtue of "introduction of a rotaxane compound into a hydrogel composition", the hydrogel composition and the hydrogel lens of the present disclosure can have effects of loading and slowly releasing active ingredients.

Claim 1:
A hydrogel composition (<NUM>), characterized by comprising:
a hydrophilic monomer (<NUM>), a content range of the hydrophilic monomer (<NUM>) in the hydrogel composition (<NUM>) being between <NUM> wt% and <NUM> wt.% based on a total weight of the hydrogel composition (<NUM>);
a cross-linker, a content range of the cross-linker in the hydrogel composition (<NUM>) being between <NUM> wt% and <NUM> wt% based on the total weight of the hydrogel composition (<NUM>);
an initiator, a content range of the initiator in the hydrogel composition (<NUM>) being between <NUM> wt% and <NUM> wt% based on the total weight of the hydrogel composition (<NUM>); and
a rotaxane compound (<NUM>), a content range of the rotaxane compound (<NUM>) in the hydrogel composition (<NUM>) being between <NUM> wt% and <NUM> wt% based on the total weight of the hydrogel composition (<NUM>); wherein the rotaxane compound (<NUM>) includes at least one cyclic molecule (<NUM>) and at least one linear molecule (<NUM>) passing through the at least one cyclic molecule (<NUM>) in a string manner;
wherein a weight ratio of the rotaxane compound (<NUM>) relative to the hydrophilic monomer (<NUM>) is between <NUM>:<NUM> and <NUM>:<NUM>;
wherein, in the rotaxane compound (<NUM>), a number average molecular weight of the linear molecule (<NUM>) is between <NUM>,<NUM> and <NUM>,<NUM>, and the rotaxane compound (<NUM>) does not include any slopper or capping used for preventing the cyclic molecule (<NUM>) from detaching from two ends of the linear molecule (<NUM>).