Contact lenses releasing fatty acids continuously

Abstract

Described herein is a fatty acid-releasing contact lens and a method of making the same. The fatty acid-releasing contact lens comprises a glycerophospholipid loaded to a polymeric lens body and continuously releases C 12 - C 26 fatty acids in a release medium comprising a sPLA2 enzyme solution for 1 hour. The fatty acid-releasing contact lens can be comfortably worn by a contact lens wearer and can increase the duration of comfortable lens wear and / or reduce lens awareness events in a contact lens wearer.

Description

Technical Field

[0001] The field of this invention relates to contact lenses, and in particular, to contact lenses that are more comfortable for contact lens wearers. Background Technology

[0002] It is estimated that 50% of all contact lens wearers experience discomfort while wearing their lenses, and approximately 25% of these wearers permanently discontinue wearing them. Lens sensation is a major cause of dissatisfaction among contact lens wearers. Despite advancements in contact lens materials, there is still a need for improved contact lenses that can be comfortably worn by wearers who experience lens sensation in a different way when wearing currently available contact lenses.

[0003] Fatty acids are known to act as comfort agents, providing lubrication and relieving discomfort when applied to the eyes. These comfort agents can be released from contact lenses in amounts sufficient to desensitize the eyes and thus reduce discomfort during wear (U.S. Patent Application Publication No. 20220187620). However, some contact lens materials cannot maintain fatty acid release throughout the entire day.

[0004] It is desirable to achieve a sustained rate of fatty acid release from the contact lens throughout the entire duration of contact lens wear, thereby increasing the duration during which the contact lens wearer can comfortably wear the contact lens. Alternatively, it is desirable to provide an improved contact lens that can be worn by the contact lens wearer. Summary of the Invention

[0005] One feature of this invention is to provide a hydrogel contact lens that releases fatty acids, especially C, during lens wear. 12 -C 26 Fatty acids, such as oleic acid.

[0006] Another feature of the invention is that it provides contact lenses that can be comfortably worn by contact lens wearers.

[0007] Another feature of the invention is to increase the duration of comfortable glasses wear and / or reduce glasses-sensing events in contact lens wearers.

[0008] Further features and advantages of the invention will be set forth in part in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and obtained by means of the components and combinations particularly pointed out in this description and the appended claims.

[0009] To achieve these and other advantages and in accordance with the purposes of the invention, as embodied and broadly described herein, this invention relates in part to a hydrogel contact lens comprising a polymer lens body loaded with phospholipids, wherein the phospholipids are C12 -C 26 Glycerophospholipids with an acyl group at the sn-2 position. These phospholipids are advantageously readily digested by secretory phospholipase 2-acylhydrolase (sPLA2) enzymes (especially group IIA secretory phospholipase 2-acylhydrolase (sPLA2-IIA)) found in human tears. Phospholipids present in the contact lens body are advantageously glycerophospholipids readily digested by sPLA2 enzymes (especially sPLA2-IIA) found in human tears when present in the polymer lens body of hydrogel contact lenses, especially polysiloxane hydrogel contact lenses, such as Stenfilcon A contact lenses. After immersing identical Stenfilcon A contact lenses, each loaded with the glycerophospholipids, in each release medium for 4 hours at 35°C, C-terminated phospholipids derived from the digestion of the acyl group at the sn-2 position are obtained when released from Stenfilcon A lenses loaded with at least 200 μg of glycerophospholipids into an artificial tear (ATF) release medium containing sPLA2 enzyme. 12 -C 26 The amount of fatty acids released into the control ATF release medium, which was otherwise identical and lacked phospholipase A2 enzyme, was C. 12 -C 26 When the amount of fatty acids is at least 3 times, it contains C. 12 -C 26Glycerophospholipids with the acyl group at the sn-2 position are considered readily digestible by the sPLA2 enzyme. An exemplary ATF release medium containing the sPLA2 enzyme may be another release medium containing 50 ppm of recombinant human sPLA2-IIA as defined in Table 1 below, and a control release medium lacking the phospholipase A2 enzyme may be an ATF release medium otherwise identical to the sPLA2 enzyme. Alternatively, the release medium containing the sPLA2 enzyme may be a reflex tear solution, while the control release medium may be ATF. For the avoidance of doubt, although the ease with which glycerophospholipids are digested by the sPLA2 enzyme can be determined by loading glycerophospholipids onto Steinfeld A lenses, the contact lenses of the present invention (including contact lenses containing glycerophospholipids determined to be readily digestible by the sPLA2 enzyme) need not be Steinfeld A lenses. In all aspects of the invention, contact lenses in which glycerophospholipids are readily digestible by the sPLA2 enzyme may be any contact lenses described herein. An example of a phospholipid that is not easily digested by the sPLA2 enzyme, which is found in human tears, when present in the body of a polysiloxane hydrogel contact lens is, for example, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) from the phosphatidylcholine family. The phospholipid present in the contact lens body is advantageously not DMPC. The phospholipid present in the contact lens body may not be DMPC or DOPC. The phospholipid present in the contact lens body may not be glycerophosphocholine or not phosphocholine. The phospholipid may be anionic glycerophospholipid or zwitterionic glycerophospholipid. Anionic glycerophospholipids include groups attached to the phospholipid head (i.e., in R...). 3 The phospholipid may be an anionic (negatively charged) substrate group (position).

[0010]

[0011] Where X is –O– or –O(CO)–, R 1 and R 2 Each independently is C 11-25 Alkyl, R 3 It is selected from hydrogen; C 1-10 Polyols (e.g., glycerol or inositol); ethanolamine (-CH2CH2NH2); and serine (-CH2CH(NH2)COOH), and salts of phospholipids of formula (I) (e.g., where R...). 3 It is a negatively charged or deprotonated anionic group (e.g., -CH2CH(NH2)COO). - Preferably, R 3 It is not choline, that is, the glycerophospholipid is not 1,2-dioleoyl-sn-glycero-3-phosphocholine. It has been found that the hydrogel contact lenses of the present invention continuously release C... 12-C 26 Fatty acids, thereby enhancing the comfort of contact lenses in eyeglass wearers and / or increasing the duration of comfortable contact lens wear in contact lens wearers.

[0012] In one example, after the hydrogel contact lens was immersed at 35°C in an ATF release medium containing 50 ppm sPLA2-IIA enzyme solution in phosphate-buffered saline (PBS) for 1 hour, the hydrogel contact lens was able to release 0.01 μg to 50 μg, 0.05 μg to 40 μg, and especially 0.1 μg to 25 μg of C. 12 -C 26 fatty acid.

[0013] Furthermore, the present invention relates to a method for manufacturing the hydrogel contact lenses of the present invention. The method includes the following steps: a) polymerizing a polymerizable composition (as described herein) in a contact lens mold to obtain a polymeric lens body; b) removing the polymeric lens body from the contact lens mold; c) placing the polymeric lens body in a container containing C... 12 -C 26 The process involves: d) extracting the acyl group in an organic solvent containing glycerophospholipids at the sn-2 position; d) hydrating the polymer eyeglass body in an hydration liquid to obtain a hydrogel contact lens; e) sealing the hydrogel contact lens in a package using a packaging solution; and f) vaporizing the package. The hydration step d) may occur prior to the extraction step c) in which the phospholipids are loaded onto the polymer eyeglass body. If the hydration step d) occurs prior to the extraction step c) in which the phospholipids are loaded onto the polymer eyeglass body, then an additional hydration step may be performed after step c).

[0014] Furthermore, the present invention relates to a method for providing symptomatic contact lens wearers with a polymer eyeglass body load comprising C 12 -C 26 Release of glycerophospholipids with acyl groups at the sn-2 position (C) 12 -C 26 Hydrogel contact lenses containing fatty acids (especially oleic acid-releasing hydrogel contact lenses) are a method for correcting vision in symptomatic contact lens wearers. Advantageously, compared to those without C... 12 -C 26A control lens of glycerophospholipids with an acyl group at the sn-2 position, the hydrogel contact lens that releases fatty acids increases the duration of comfortable contact lens wear and / or reduces lens-perceived events in symptomatic contact lens wearers. The phospholipid is advantageously a glycerophospholipid readily digestible by sPLA2 enzymes (especially sPLA2-IIA) found in human tears when present in the polymeric lens body, such as glycerophospholipid of formula (I). As used herein, “symptomatic contact lens wearer” refers to a lens wearer classified as symptomatic using the CLDEQ-8 as described by Chalmers et al. (see Chalmers et al., Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance. Optom Vis Sci 2012; 89(10):1435-1442.).

[0015] Furthermore, this invention relates to contact lens wearers using lenses containing C 12 -C 26 Release of glycerophospholipids with acyl groups at the sn-2 position (C) 12 -C 26 Hydrogel contact lenses containing fatty acids, compared to those without C... 12 -C 26 A control of glycerophospholipids with acyl groups at the sn-2 position in contact lenses increases the duration of comfortable contact lens wear and / or reduces eye-sensing events.

[0016] Furthermore, the present invention relates to a quantity containing C 12 -C 26 Use of glycerophospholipids with acyl groups at the sn-2 position for enhancing the comfort of contact lenses, wherein the glycerophospholipids are associated with the polymeric lens body of the contact lens.

[0017] Furthermore, the present invention relates to a hydrogel composition for reducing lens perception in contact lens wearers, thereby enhancing the comfort of the contact lens in the wearer and / or increasing the duration of comfortable contact lens wear in the wearer, the composition comprising (a) a polymeric lens body for polymerizing the reaction product of the composition, and (b) a loading of an amount of C 12 -C 26 Glycerophospholipids with an acyl group at the sn-2 position.

[0018] In all aspects of the invention, C is included. 12 -C 26Glycerophospholipids with the acyl group at the sn-2 position are advantageously readily digestible by sPLA2 enzymes (especially group IIA sPLA2) found in human tears when present in the polymer lens body of hydrogel contact lenses (especially polysiloxane hydrogel contact lenses). In all aspects of the invention, the polymer lens body is loaded with C... 12 -C 26 The contact lens with an acyl group at the sn-2 position is characterized by: (a) when the contact lens is immersed in human reflex tears at 35°C for 4 hours, compared to when the lens is immersed in an ATF release medium lacking phospholipase A2 enzyme at 35°C for 4 hours, a 3-fold increase in C is detected in the reflex tears. 12 -C 26 Fatty acid degradation products; and / or (b) when the contact lenses were immersed at 35°C in an ATF release medium containing 50 ppm recombinant human group IIa phospholipase A2 for 4 hours, compared with when the lenses were immersed at 35°C in an equivalent ATF release medium lacking phospholipase A2 for 4 hours, three times the amount of C was detected in the reflex tears. 12 -C 26 Fatty acid degradation products. The phospholipids are typically glycerophospholipids, such as glycerophospholipid of formula (I):

[0019]

[0020] Where X is –O– or –O(CO)–, R 1 and R 2 Each independently is C 11-25 Alkyl, R 3 The radical is selected from hydrogen, C 1-10 Polyols, ethanolamines (-CH2CH2NH2), and serine (-CH2CH(NH2)COOH), and their salts (e.g., where R... 2 The ethanolamine is negatively charged, or it is protonated to form -CH2CH2NH3. + ).

[0021] Other aspects of the invention are provided in the following numbered entries:

[0022] 1. An unworn hydrogel contact lens sealed in packaging, the contact lens comprising a polymer lens body and a load comprising C 12 -C 26 Glycerophospholipids with an acyl group at the sn-2 position.

[0023] 2. The contact lens of claim 1, wherein the glycerophospholipids, when present in the polymer lens body, are readily digested by secretory phospholipase A2 (sPLA2) enzyme found in human tears.

[0024] 3. The contact lens as described in clause 1 or 2, wherein the glycerophospholipid is of formula (I):

[0025]

[0026] Where X is –O– or –O(CO)–, R 1 and R 2 Each independently is C 11-25 Alkyl and R 3 The radical is selected from hydrogen, C 1-10 Polyols, ethanolamines, and serine, and their salts.

[0027] 4. Contact lenses as described in item 3, wherein R 1 and R 2 Each independently is C 13-21 alkyl.

[0028] 5. The contact lens of any of the preceding clauses, wherein the glycerophospholipid is phosphatidylserine, phosphatidylethanolamine, or phosphatidylglycerol.

[0029] 6. The contact lens of paragraph 5, wherein the glycerophospholipid is phosphatidylglycerol, especially 1,2-dioleoylphosphatidylglycerol, 1-palmitoyl-2-oleoylphosphatidylglycerol, 1-stearoyl-2-oleoyl or 1,2-bis(docosahexaenoyl)phosphatidylglycerol.

[0030] 7. The contact lens described in any of clauses 1 to 4, wherein the glycerophospholipid is not dimyristoylphosphatidylcholine (DMPC).

[0031] 8. The contact lens described in any of clauses 1 to 4, wherein the glycerophospholipid is not phosphatidylcholine.

[0032] 9. The contact lens as described in any of clauses 1 to 8, wherein the contact lens is a polysiloxane hydrogel contact lens.

[0033] 10. Contact lenses as described in any of items 1 to 9, wherein the hydrogel is neutral or cationic.

[0034] 11. A contact lens as described in any one of clauses 1 to 10, wherein the polymeric lens body is a reaction product comprising at least one polymerizable composition containing a hydrophilic monomer comprising a vinyl group.

[0035] 12. A contact lens as described in any one of clauses 1 to 11, wherein the polymer lens body comprises a first siloxane having a structure represented by formula (II),

[0036]

[0037] The reaction product of a polymerizable composition of a second siloxane having a structure represented by formula (III),

[0038]

[0039] 13. The contact lens according to any of the preceding clauses, wherein the hydrogel contact lens releases C upon contact with a solution containing sPLA2-IIA. 12 -C 26 Fatty acids and their salts, of which C 12 -C 26 The fatty acids are digestion products of the glycerophospholipids.

[0040] 14. The contact lens according to any of the preceding clauses, wherein the polymer lens body is loaded with an amount of glycerophospholipids ranging from 1 μg to 1000 μg, preferably from 25 μg to 300 μg.

[0041] 15. The contact lens according to any of the preceding clauses, wherein when the contact lens is immersed at 35°C in a release medium comprising artificial tears containing 50 ppm PLA2-IIA, the contact lens continuously releases at least 0.05 μg / hr C. 12 -C 26 Fatty acids, especially at least 0.1 μg / hr C 12 -C 26 Fatty acids or 1 μg / hr C 12 -C 26 Fatty acids, for at least 4 hours, for example at least 8 hours, optionally at least 10 hours.

[0042] 17. The contact lens of any of the preceding clauses has a balanced water content of at least 40%.

[0043] 18. The contact lens as described in any of the preceding clauses, wherein the packaging comprises:

[0044] (a) A base component having a cavity for retaining the packaged solution; and

[0045] (b) A cover, which forms a liquid-tight seal with the base component.

[0046] 19. A method of manufacturing a hydrogel contact lens as described in any of the preceding claims, the method comprising: a) polymerizing a polymerizable composition in a contact lens mold to obtain a polymeric lens body; b) removing the polymeric lens body from the contact lens mold; c) placing the polymeric lens body in a container containing C 12 -C 26The acyl group is extracted in an organic solvent from the glycerophospholipid at the sn-2 position; d) the polymer eyeglass body is hydrated in an aqueous liquid to obtain the hydrogel contact lens; e) the hydrogel contact lens is sealed in a package with a packaging solution; and optionally, f) the package is vapor-treated.

[0047] 20. A method for correcting the vision of a symptomatic contact lens wearer, the method comprising the symptomatic contact lens wearer of a hydrogel contact lens as described in any one of items 1 to 18.

[0048] 21. The method of clause 20, wherein the symptomatic contact lens wearer has an increased duration of comfortable contact lens wear compared to the control lens.

[0049] 22. The method of paragraph 20 or 21, wherein the symptomatic contact lens wearer has reduced lens perception and / or fewer “lens perception events” during the day compared to the control lens.

[0050] 23. A quantity containing C 12 -C 26 Use of glycerophospholipids with acyl groups at the sn-2 position for enhancing the comfort of contact lenses, wherein the glycerophospholipids are associated with the polymeric lens body of the contact lens.

[0051] 24. As described in paragraph 23, wherein the contact lens is a hydrogel contact lens as described in any one of paragraphs 1 to 16.

[0052] 25. As used in paragraph 23 or 24, wherein the perception of the contact lens is reduced in the contact lens wearer, thereby enhancing the comfort of the contact lens in the symptomatic contact lens wearer and / or increasing the duration of comfortable contact lens wear in the symptomatic contact lens wearer.

[0053] 26. A hydrogel composition for reducing lens perception in a contact lens wearer, thereby enhancing the comfort of the contact lens in the contact lens wearer and / or increasing the duration of comfortable contact lens wear in the contact lens wearer, said composition comprising (a) a polymeric lens body of a reaction product capable of polymerizing the composition, and (b) a loading of an amount of C 12 -C 26 Glycerophospholipids with an acyl group at the sn-2 position.

[0054] 27. The composition used as described in paragraph 26, wherein the composition is in the form of a contact lens as described in any one of paragraphs 1 to 18. Attached Figure Description

[0055] Figure 1The derivatization of dioleoylphosphatidylglycerol (DOPG) via PLA2 enzymatic hydrolysis at the sn-2 ester bond yields oleic acid and lysophosphatidylglycerol (LOPG).

[0056] Figure 2 Plot the oleic acid release curve of a 5 mg / mL DOPG-loaded polysiloxane hydrogel contact lens (lens A) in ATF containing 50 ppm PLA2 enzyme solution.

[0057] Figure 3 Plot the oleic acid release profile of a 3 mg / mL DOPG-loaded polysiloxane hydrogel contact lens (Glasses B) in ATF containing 50 ppm sPLA2 enzyme solution. Detailed Implementation

[0058] This article describes the continuous release of C during wear. 12 -C 26 Hydrogel contact lenses containing fatty acids and a method for their manufacture. The contact lenses herein may be referred to as C-released fatty acid contact lenses. 12 -C 26 Fatty acid contact lenses. C 12 -C 26 Fatty acids are released from the contact lenses during wear in an amount that enhances the comfort of contact lens wearers and can increase the duration during which contact lens wearers can comfortably wear contact lenses. Specifically, the release of C from the present invention... 12 -C 26 Fatty acid-based glasses can increase all-day comfort of eyeglass wear in symptomatic patients. The C... 12 -C 26 Fatty acids can act as TRPV1 antagonists, such as oleic acid.

[0059] The present invention advantageously provides C from hydrogel contact lenses 12 -C 26 Fatty acids are continuously released, including glycerophospholipids (such as oleic acid-containing glycerophospholipids) associated with hydrogel contact lenses, which break down to release C. 12 -C 26 Fatty acids, especially oleic acid. For effective vitamin C... 12 -C 26 Fatty acid release rate, the C 12 -C 26 The fatty acid group must occupy the sn-2 (middle) position in the glycerophospholipid structure. 12 -C 26A fatty alcohol or fatty acid group may occupy the sn-1 (terminal) position in the glycerophospholipid structure. The sn-1 fatty acid may be a substitute fatty acid for the fatty acid at the sn-2 position, i.e., a fatty acid with a different number of carbon atoms. For example, the fatty acid at the sn-2 position may be oleic acid or docosahexaenoic acid, and the fatty acid at the sn-1 position may be a fatty acid other than oleic acid or docosahexaenoic acid. In one example, the glycerophospholipid is 2-oleoylglycerol phospholipid, particularly 2-oleoylphosphatidylglycerol, such as sodium 1,2-dioleoyl-sn-glycerol-3-phosphate-rac-(1-glycerol) (DOPG). In another example, the glycerophospholipid is 2-docosahexaenoylphosphatidylglycerol, such as 1,2-bis(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-4,7,10,13,16,19-hexaenoylsn-glycerol-3-phosphate-rac-(1-glycerol)sodium salt (DHA-PG). In examples of DOPG, oleic acid is a fatty acid at the sn-1 and sn-2 positions of the phosphatidylglycerol. Figure 1 As shown in the study, when DOPG load glasses are placed on the eyes, DOPG is degraded by the tear enzyme sPLA2-IIA.

[0060] C is contained at position sn-2. 12 -C 26Acyl glycerophospholipids can be degraded by group IIA secretory phospholipase A2 (sPLA2-IIA), an enzyme found in human tears. The glycerophospholipids may be, for example, phosphatidic acid, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, or diphosphatidylglycerol. Preferably, the glycerophospholipids are not phosphoric acid choline. Phosphocholine has been found to be less susceptible to degradation by group IIA sPLA2-IIA enzymes found in human tears compared to other glycerophospholipids. Advantageously, the glycerophospholipids are selected from phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylglycerol, especially phosphatidylethanolamine or phosphatidylglycerol. The pKa of the amino group of phosphatidylethanolamine (PE) or phosphatidylserine (PS) is preferably in the range of 8 to 10, more preferably in the range of 8.5 to 9.8. Further information on the activity of sPLA2 enzymes can be found in Chemical Review, 12 October 2011; 111(10):6130–6185, “Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention”, Dennis et al.

[0061] Regarding "easily digestible", sPLA2, which is present in human tears, hydrolyzes the acyl group at the sn2 position of glycerophospholipids, thereby producing free fatty acids and lysophospholipids.

[0062] The glycerophospholipids can be digested by human tears. The glycerophospholipids can be digested by sPLA2, which is present in at least human tears.

[0063] C at position sn-2 12 -C 26 Fatty acids are advantageously released and eluted from the eyeglasses, while the remainder of the glycerophospholipids remains inside the eyeglasses. (Except for C) 12 -C 26 In addition to the diffusion rate of the fatty acid itself, the C 12 -C 26 The release rate of fatty acids can be determined based on the kinetics of the enzymatic reaction of the phospholipids. In one embodiment, the hydrogel contact lens comprises a polymer lens body-loaded with formula (Ia)2-oleoylglycerol phospholipid:

[0064]

[0065] Where X is –O– or –O(CO)–, R 1 C 11-25 Alkyl, R 3 The radical is selected from hydrogen, C 1-10 Polyols, ethanolamines (-CH2CH2NH2), and serine (-CH2CH(NH2)COOH), and their salts (e.g., R). 3 The ethanol is negatively charged, or the ethanol is protonated to -CH2CH2NH3. + R 3 Preferably selected from -CH2CH2NH2, -CH2CH(NH2)COOH and –CH2CH(OH)CH2OH, especially –CH2CH(OH)CH2OH. 1 It can be selected, for example, from oleoyl, myristoyl, pentadecanoyl, palmitoyl or stearoyl.

[0066] The release of C 12 -C 26 Fatty acid contact lenses contain a polymer lens body loaded with a amount of C. 12 -C 26 A glycerophospholipid with an acyl group at the sn-2 position, which continuously releases C from the glasses upon contact with a tear solution containing sPLA2-IIA. 12 -C 26 Fatty acids. The tear solution may be human reflex tears or an in vitro release medium containing an ATF containing, for example, a group IIA sPLA2 enzyme solution at a concentration of 50 ppm.

[0067] As an option, one or more glycerophospholipids as described herein may be present in the release C of the present invention. 12 -C 26 Fatty acids in contact lenses (e.g., two, three, or more different glycerophospholipids as described herein).

[0068] As an example, the contact lens is a non-polysiloxane hydrogel that is free of or substantially free of silicon-containing components, and is a reaction product of a polymerizable composition of a non-polysiloxane hydrogel. A hydrogel containing less than 3% by weight, particularly less than 2% by weight, and preferably less than 1% by weight of units derived from silicon-containing monomers or macromonomers is a non-polysiloxane hydrogel that is substantially free of silicon-containing components. Non-polysiloxane hydrogel contact lenses are typically formed from the polymerization of one or more hydrophilic monomers (e.g., 2-hydroxyethyl methacrylate (HEMA) or vinyl alcohol) optionally in combination with other monomers, and are free of siloxane molecules. The polymeric lens body of the hydrogel contact lens may, for example, be a reaction product of a polymerizable composition comprising at least one monomer selected from N-vinylpyrrolidone, (hydroxyethyl) methacrylate, glycidyl methacrylate, ethylene glycol dimethacrylate, and / or polycarbonate, or any combination thereof, wherein the composition optionally is free of siloxane monomers or macromonomers.

[0069] The hydrogel contact lens may be a polysiloxane hydrogel. As an example, the polysiloxane hydrogel contact lens comprises a polymeric lens body, which is a reaction product of a polymerizable composition comprising at least one siloxane monomer or macromonomer and at least one hydrophilic monomer and / or at least one hydrophilic polymer. Conveniently, as described in more detail below, the cured polymeric lens body for the polysiloxane hydrogel can be extracted in an extraction solvent containing glycerophospholipids. Thus, the desired amount of glycerophospholipids becomes associated with the polymeric lens body. The glycerophospholipids can adhere to the polymeric lens body via electrostatic and / or hydrophobic interactions, and / or can be physically embedded through the polymeric network of the polymeric lens body. Alternatively, or additionally, the glycerophospholipids can be added to the polymerizable composition, for example, prior to curing.

[0070] Advantageously, the hydrogel (i.e., conventional hydrogel or polysiloxane hydrogel) is neutral or positively charged (i.e., cationic), preferably neutral. The term "neutral" refers to a unit derived from nonionic or zwitterionic molecules. It has been found that the presence of an overall negative charge inhibits the activity of the sPLA2 enzyme and thus reduces C. 12 -C 26 Fatty acids are released from the glycerophospholipid-containing contact lenses. Preferably, the contact lenses do not contain anionic units, such as units derived from methacrylic acid (MAA) or 2-methacryloyloxyethyl phosphate (MOEP).

[0071] The polymer lens body typically has an equilibrium water content (EWC) of at least 40%, for example, at least 45%. Advantageously, the hydrogel contact lens is a high water content contact lens with a polymer lens body having an EWC of at least 50%. The contact lens may be a US Food and Drug Administration (FDA) Group II nonionic high water content lens or an FDA Group IV ionic high water content lens, which is a cationic or polysiloxane hydrogel contact lens with an EWC of at least 40% or at least 45%. Advantageously, the contact lens is an FDA Group II nonionic high water content lens or a polysiloxane hydrogel contact lens with an EWC of at least 40% or at least 45%. It has been found that an EWC greater than 40% results in increased sPLA2 enzyme activity, leading to fatty acid release.

[0072] The amount of glycerophospholipids “loaded onto” or “associated with” the polymer eyeglass body refers to the total amount of glycerophospholipids that can be extracted from the contact lens by the isopropanol (IPA) extraction method described in Example 2 below. The glycerophospholipids associated with the polymer eyeglass body may be embedded in the matrix of the polymer material or attached to the polymer material, for example, through hydrogen bonding or electrostatic interactions. Advantageously, when the eyeglasses are immersed in deionized water or a standard contact lens packaging solution (e.g., phosphate-buffered saline or phosphate-buffered saline containing 75 ppm polyvinylpyrrolidone (PVP), the glycerophospholipids associated with the polymer eyeglass body are not removed. Advantageously, when the eyeglasses are immersed in 5 mL of deionized water, no more than 20% by weight, and especially no more than 10% by weight, of the glycerophospholipids are extracted from the polymer eyeglass body into the deionized water. In one example, the glycerophospholipids are loaded onto the polymer eyeglass body in a loading solution containing an alcohol (e.g., ethanol) and 2-oleoylphospholipids in the range of 1 to 10 mg / mL. The loading solution may, for example, contain about 60% ethanol and about 40% water. In one particular example, the loading solution contains 2 mg / mL glycerophospholipids. The eyeglasses can be immersed in the loading solution at 25°C for 3 hours to load the glycerophospholipids onto the polymer eyeglass body. In another example, the amount of 2-oleoylphospholipids associated with the polymer eyeglass body may be at least about 1 μg, 25 μg, 50 μg, 100 μg, 200 μg, or 300 μg, up to about 400 μg, 500 μg, 600 μg, 700 μg, 800 μg, 900 μg, or 1000 μg, for example, about 300 μg to about 1000 μg. Preferably, the amount of glycerophospholipids associated with the polymer eyeglass body is 100 μg to 1000 μg, particularly 300 μg to 800 μg.

[0073] The glycerophospholipid may have formula (I):

[0074]

[0075] Where X is –O– or –O(CO)–, R 1 and R 2 Each independently is C 11-25 Alkyl, and R 3 It is selected from hydrogen, C 1-10 Polyols, ethanolamines (-CH2CH2NH2) and serine (-CH2CH(NH2)COOH), or salts of glycerophospholipids of formula (I) (e.g., where R...) 3 It is a negative charge, or R 3 For protonated ethanolamine: -CH2CH2NH3 + ).

[0076] R 1 and R 2 Each is independently a saturated or unsaturated alkyl group. Unless otherwise stated, the term "alkyl" as used herein refers to an aliphatic group having a saturated alkyl chain and a group having an unsaturated alkenyl chain. R 1 and R 2 Each can independently have a straight-chain (i.e., unbranched) or branched alkyl or alkenyl chain. R 1 and R 2 Each is independently unsubstituted or substituted, for example via hydroxyl, C 1-12 Alkyl groups (e.g., methyl, ethyl, propyl, or butyl), polyethylene glycol (PEG), sugars, epoxy groups, and any combination thereof are substituted, especially unsubstituted or substituted with hydroxyl or methyl groups. Optionally, R 1 and R 2 Each independently is C 11-23 Especially for C 13-21 Alkyl, wherein R 1 and R 2 Each is independently, optionally unsaturated, and contains at least one unsaturated C=C double bond. Optionally, R 1 and R 2 Each is independently -(CH2) 7-11 CH=CH(CH2) 1-9 CH3, or -(CH2) 8-10 CH=CH(CH2) 1-7 CH3, for example -(CH2) 10 CH=CH(CH2)1CH3, -(CH2)8CH=CH(CH2)7CH3 or -(CH2) 10 CH=CH(CH2)3CH3. Optionally, R 1 and R 2Each is independently an oleoyl group and oleic acid, having the IUPAC name: (9Z)-octadec-9-enoic acid. Optionally, R 1 and R 2 Each is independently -(CH2) 1-4 [CH=CH(CH2) 1-2 ] 3-7 CH3, for example -(CH2)2[CH=CH(CH2)]6CH3. Optionally, R 1 and R 2 Each is independently a docosahexaenoyl group and a docosahexaenoic acid, having the IUPAC name (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid. Advantageously, R 2 C 11-25 Unsaturated alkyl groups, preferably C 11-23 Alkyl groups, for example, containing at least one unsaturated C=C double bond, preferably one C=C double bond. 13-21 Alkyl group. R 2 Optionally, it has a straight-chain (i.e., unbranched) alkyl chain. Optionally, R 2 -(CH2) 7-11 CH=CH(CH2) 1-9 CH3 or -(CH2) 8-10 CH=CH(CH2) 1-7 CH3, for example -(CH2) 10 CH=CH(CH2)1CH3, -(CH2)8CH=CH(CH2)7CH3 or -(CH2) 10 CH=CH(CH2)3CH3. R 2 It can be selected from oleoyl, palmitoyl, stearoyl, or docosahexaenoyl, such as oleoyl or docosahexaenoyl, especially oleoyl. Advantageously, R 1 C 11-25 Unsaturated alkyl groups, preferably C10, are preferred. 11-23 Alkyl groups, for example, containing at least one unsaturated C=C double bond, preferably one C=C double bond. 13-21 Alkyl group. Optionally, R 1 It has a straight-chain (i.e., unbranched) alkyl chain. Optionally, R 1 -(CH2) 7-11 CH=CH(CH2) 1-9 CH3 or -(CH2) 8-10 CH=CH(CH2) 1-7 CH3, for example -(CH2) 10 CH=CH(CH2)1CH3, -(CH2)8CH=CH(CH2)7CH3 or -(CH2)10 CH=CH(CH2)3CH3. R 1 It can be selected from oleoyl, palmitoyl, stearoyl or docosahexaenoyl.

[0077] R 3 Selected from hydrogen, C 1-10 Polyols, ethanolamines (-CH2CH2NH2) and serine (-CH2CH(NH2)COOH) and their salts, especially C 1-10 The groups of polyols and ethanolamines (-CH2CH2NH2) and their salts. R 3 Advantageously selected from -CH2CH2NH2 and -CH2CH(OH)CH2OH. The polyol is an organic compound containing multiple hydroxyl groups. Optionally, the glycerophospholipid is a phosphatidylglycerol. Non-limiting examples of suitable glycerophospholipids include 1,2-dioleoylphosphatidylglycerol, 1,2-dimyristoylphosphatidylglycerol, 1,2-di(pentadecanoyl)phosphatidylglycerol, 1-myristoyl-2-oleoylphosphatidylglycerol, 1-pentadecanoyl-2-oleoylphosphatidylglycerol, 1-palmitoyl-2-oleoylphosphatidylglycerol, 1-stearoyl-2-oleoylphosphatidylglycerol, 1,2-di(docosahexaenoic acid) (Oleyl) phosphatidylglycerol, 1-myristoyl-2-docoshexaenoyl phosphatidylglycerol, 1-pentadecanoyl-2-docoshexaenoyl phosphatidylglycerol, 1-palmitoyl-2-docoshexaenoyl phosphatidylglycerol, 1-stearoyl-2-docoshexaenoyl phosphatidylglycerol, 1-docoshexaenoyl-2-oleoyl phosphatidylglycerol, and 1-oleoyl-2-docoshexaenoyl phosphatidylglycerol. 2-oleoyl phosphatidylglycerol, such as 1,2-dioleoyl phosphatidylglycerol, has been found to be particularly suitable.

[0078] As used herein and unless the context otherwise indicates, references to the release of C during a specific period of time are made. 12-26 Fatty acids released by contact lenses 12 -C 26 The amount of fatty acids or the C mentioned above 12 -C 26 The "release curve" of fatty acids refers to the amount of C released from the glasses, measured using an in vitro release medium (ATF containing 50 ppm PLA2-IIA (e.g., recombinant human group IIA phospholipase 2-acyl hydrolase enzyme or bee venom sPLA2) as described in Table 1 below, as in Example 4 below). 12 -C 26 The amount of fatty acids. The contact lens, after initial immersion in the release medium at 35°C, may have a concentration ranging from at least 0.05 μg / hr, or from 0.05 μg / hr to 50 μg / hr. 12-26Fatty acids, for example, from 0.1 μg / hr to 25 μg / hr, or 0.5 μg / hr to 10 μg / hr, or 1 μg / hr to 5 μg / hr of the eyeglasses. 12 -C 26 In vitro C of fatty acids 12-26 Fatty acid release curve. Advantageously, the contact lens continuously releases C... 12-26 Fatty acids, for at least 4 hours, for example at least 8 hours, optionally at least 10 hours. Advantageously, the contact lens releases 0.05 μg / hr to 50 μg / hr of C from the lens for at least the first 10 hours after immersion in the release medium at 35°C. 12-26 Fatty acids, for example, 0.01 μg / hr to 25 μg / hr, or 0.5 μg / hr to 10 μg / hr, or 1 μg / hr to 5 μg / hr C 12 -C 26 Fatty acids. Therefore, the phospholipid-loaded (I) phospholipid contact lenses of the present invention can have a duration of at least 4 hours, for example at least 8 hours, optionally at least 10 hours, from the lenses at a concentration of at least 0.05 μg / hr, preferably at least 0.1 μg / hr, for example from 0.1 μg / hr to 25 μg / hr, for example from 0.5 μg / hr to 10 μg / hr, or from 1 μg / hr to 5 μg / hr. 12 -C 26 In vitro C of fatty acids 12-26 Fatty acid release profiles were obtained by placing the glasses in a 6 mL glass file containing 3 mL of in vitro release medium (ATF with 50 ppm sPLA2 added as described in Table 1), shaking the vial at 50 rpm in a 35°C incubator, and removing 2.5 mL of release medium sample from the vial in 2-hour increments (e.g., 2hr, 4hr, 6hr, 8hr, and 10hr) and analyzing the C4 concentration of the sample by liquid chromatography-mass spectrometry (LCMS). 12 -C 26 The fatty acid content and 2.5 ml of fresh release medium were replaced into a vial, and the glasses were incubated in the vial in the shaker for another 2 hours until the next increment was determined.

[0079] As an option, the contact lenses of the present invention do not contain any comfort agents other than the glycerophospholipids described herein.

[0080] As an option, the contact lenses of the present invention may contain one or more comfort agents different from those described herein, such as glycerophospholipids. The amount of any other comfort agent may be less than the amount of glycerophospholipids present. The amount of any other comfort agent may be less than 300 μg, less than 100 μg, less than 50 μg, less than 10 μg, or less than 1 μg.

[0081] As an option, the packaged solution described herein does not contain any comfort agents.

[0082] As an option, the packaging solution described herein does not contain any comfort agents, except that it may contain glycerophospholipids and / or fatty acids resulting from the glycerophospholipids originally present in the contact lenses.

[0083] As an option, the only phospholipid present in or associated with the contact lens is glycerophospholipid.

[0084] As an option, the only source of fatty acids released or present in the contact lenses is from the glycerophospholipids present.

[0085] Compared to free fatty acids (not derived from glycerophospholipids) associated with the contact lens, the present invention is capable of providing improved controlled release of fatty acids. For example, the release can be more linear compared to free fatty acids used / associated solely with the contact lens.

[0086] The release of fatty acids through the digestion of glycerophospholipids can be considered as the tear-controlled release of fatty acids.

[0087] The polymeric eyeglass body may contain any hydrogel material suitable for use as a contact lens material. Non-polysiloxane hydrogel materials for contact lenses are typically formed by curing a polymerizable composition (i.e., a monomer mixture) comprising at least one hydrophilic monomer or at least one hydrophilic polymer or a combination thereof. The polymerizable composition used to form the non-polysiloxane hydrogel eyeglass material is typically free of or substantially free of silicon-containing components, particularly free of or substantially free of siloxane monomers or macromonomers. The polymerizable composition used to form the non-polysiloxane hydrogel eyeglass material may contain no more than 3% by weight of silicon-containing components, particularly no more than 2% by weight, for example no more than 1% by weight. Polysiloxane hydrogel materials for contact lenses are typically formed by curing a polymerizable composition (i.e., a monomer mixture) comprising at least one siloxane monomer or macromonomer and at least one hydrophilic monomer or at least one hydrophilic polymer or a combination thereof. As used herein, the term "siloxane monomer" refers to a molecule comprising at least one Si-O group and at least one polymerizable functional group. "Siloxane macromonomers" refer to silicon-containing molecules with at least one polymerizable functional group that, although used as monomers, have a sufficiently high molecular weight and enough internal monomer units to be considered polymerizable. Typically, siloxane macromonomers contain siloxane chains with at least 5 siloxane (-Si-O-) units and / or have a molecular weight of at least 500 Daltons.

[0088] Siloxane monomers and macromonomers used in contact lens compositions are well known in the art (see, for example, U.S. Patent Nos. 8,658,747 and 6,867,245). (The full text of all patents and publications mentioned herein and throughout this document is incorporated herein by reference.) In some instances, the polymerizable composition comprises a total amount of at least 10, 20, or 30% to about 40, 50, 60, or 70% of siloxane monomers or macromonomers. Unless otherwise specified, as used herein, a given weight percentage (wt%) of a component of the polymerizable composition is relative to the total amount of all polymerizable components and interpenetrating polymer network (IPN) polymers (described further below) in the polymerizable composition. The weight of the polymerizable composition contributed by components not incorporated into the final contact lens product (e.g., diluents) is not included in the wt% calculation.

[0089] In one particular example, the polymerizable composition comprises a hydrophilic vinyl monomer. As used herein, a “hydrophilic vinyl monomer” is any non-siloxane (i.e., Si-O-free) hydrophilic monomer in which a polymerizable carbon-carbon double bond (i.e., vinyl) not part of an acrylate group exists in its molecular structure, wherein the carbon-carbon double bond of the vinyl group is less reactive in free radical polymerization than the carbon-carbon double bond present in a polymerizable methacrylate group. As used herein, the term “acrylate group” refers to a polymerizable group present in acrylates, methacrylates, acrylamides, etc. Therefore, although a carbon-carbon double bond exists in acrylate and methacrylate groups, such a polymerizable group is not considered a vinyl group as used herein. Furthermore, as used herein, a monomer is considered “hydrophilic” if, by standard shaking flask method, at least 50 grams of the monomer are completely soluble in 1 liter of water at 20°C (i.e., approximately 5% soluble in water). In various instances, the hydrophilic vinyl monomer is N-vinyl-N-methylacetamide (VMA), or N-vinylpyrrolidone (NVP), or 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or diethylene glycol vinyl ether (DEGVE), or any combination thereof. In one embodiment, the polymerizable composition comprises at least 10 wt%, 15 wt%, 20 wt%, or 25 wt% up to about 45 wt%, 60 wt%, or 75 wt% of a hydrophilic vinyl monomer. As used herein, a given weight percentage of a particular class of components (e.g., hydrophilic vinyl monomers, siloxane monomers, etc.) in the polymerizable composition is equal to the sum of the weight percentages of the components in the composition that fall within that class. Thus, for example, a polymerizable composition comprising 5 wt% BVE and 25 wt% NVP and no other hydrophilic vinyl monomers is said to comprise 30 wt% hydrophilic vinyl monomers. In one instance, the hydrophilic vinyl monomer is a vinylamide monomer. Exemplary hydrophilic vinylamide monomers are VMA and NVP. In one particular example, the polymerizable composition comprises at least 25% by weight of a vinylamide monomer. In another particular example, the polymerizable composition comprises from about 25% by weight to about 75% by weight of VMA or NVP, or combinations thereof. Other hydrophilic monomers that may be included in the polymerizable composition are N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), ethylene glycol methyl ether methacrylate (EGMA), and combinations thereof.

[0090] In addition to or as a substitute for hydrophilic monomers, the polymerizable composition may contain non-polymerizable hydrophilic polymers that produce a polymeric eyeglass body comprising an interpenetrating polymer network (IPN), wherein the non-polymerizable hydrophilic polymer interpenetrates a polysiloxane hydrogel polymer matrix. In this example, the non-polymerizable hydrophilic polymer is referred to as an IPN polymer, which is used as an internal lubricant in contact lenses. Conversely, polymer chains within a polysiloxane hydrogel network formed by the polymerization of monomers present in the polymerizable composition are not considered IPN polymers. IPN polymers may be high molecular weight hydrophilic polymers, for example, from about 50,000 to about 500,000 Daltons. In a particular example, the IPN polymer is polyvinylpyrrolidone (PVP). In other examples, the polymerizable composition is substantially free of polyvinylpyrrolidone or other IPN polymers.

[0091] As an option, one or more non-silicon-containing hydrophobic monomers may be present as part of the polymerizable composition. Hydrophobic monomers are understood to be any monomer that, when measured using the standard shaking flask method, is not completely soluble in 1 liter of water at 20°C with 50 grams of that monomer. Examples of suitable hydrophobic monomers include methyl acrylate, or ethyl acrylate, or propyl acrylate, or isopropyl acrylate, or cyclohexyl acrylate, or 2-ethylhexyl acrylate, or methyl methacrylate (MMA), or ethyl methacrylate, or propyl methacrylate, or butyl acrylate, or 2-hydroxybutyl methacrylate, or vinyl acetate, or vinyl propionate, or vinyl butyrate, or vinyl valerate, styrene, or chloroprene, or vinyl chloride, or vinylidene chloride, or acrylonitrile, or 1-butene, or butadiene, or methacrylonitrile, or vinyltoluene, or vinyl ethyl ether, or perfluorohexyl ethyl thiocarbonyl amino ethyl methacrylate, or isoborneol methacrylate (IBM), or trifluoroethyl methacrylate, or hexafluoroisopropyl methacrylate, or tetrafluoropropyl methacrylate, or hexafluorobutyl methacrylate, or any combination thereof.

[0092] The hydrophobic monomer (if used) may be present in the reaction product of the polymerizable composition in an amount of 1% to about 30% by weight (e.g., 1% to 25% by weight, 1% to 20% by weight, 1% to 15% by weight, 2% to 20% by weight, 3% to 20% by weight, 5% to 20% by weight, 5% to 15% by weight, 1% to 10% by weight) of the total weight of the polymerizable composition.

[0093] The polymerizable composition may additionally contain at least one crosslinking agent. As used herein, a "crosslinking agent" is a molecule having at least two polymerizable groups. Thus, the crosslinking agent can react with functional groups on two or more polymer chains to bridge one polymer to another. The crosslinking agent may contain acrylate or vinyl groups, or both acrylate and vinyl groups. In some instances, the crosslinking agent does not contain a siloxane portion, that is, it is a non-siloxane crosslinking agent. Various crosslinking agents suitable for use in polysiloxane hydrogel polymerizable compositions are known in the art (see, for example, U.S. Patent No. 8,231,218, which is incorporated herein by reference). Examples of suitable crosslinking agents include (but are not limited to) lower alkyl glycol di(meth)acrylates, such as triethylene glycol dimethacrylate, diethylene glycol dimethacrylate, poly(lower alkylene) glycol di(meth)acrylate and lower alkylene di(meth)acrylate; divinyl ethers, such as triethylene glycol divinyl ether, diethylene glycol divinyl ether, 1,4-butanediol divinyl ether and 1,4-cyclohexanediethanol divinyl ether; divinyl sulfone; di- and trivinylbenzene; trimethylolpropane tri(meth)acrylate; pentaerythritol tetra(meth)acrylate; bisphenol A di(meth)acrylate; methylene bis(meth)acrylamide; triallyl phthalate; 1,3-bis(3-methacryloyloxypropyl)tetramethyldisiloxane; diallyl phthalate; and combinations thereof.

[0094] As those skilled in the art will understand, polymerizable compositions may contain other polymerizable or non-polymerizable components conventionally used in contact lens formulations, such as one or more of polymerization initiators, UV absorbers, colorants, oxygen scavengers, chain transfer agents, etc. In some instances, the polymerizable composition may contain an amount of organic diluent that prevents or minimizes phase separation between the hydrophilic and hydrophobic components of the polymerizable composition to obtain optically clear lenses. Diluents commonly used in contact lens formulations include hexanol, ethanol, and / or other primary, secondary, or tertiary alcohols. In other instances, the polymerizable composition contains no or substantially no organic diluent (e.g., less than 500 ppm). In such instances, the use of siloxane monomers containing a hydrophilic moiety (e.g., a polyoxyethylene group, side hydroxyl groups, or other hydrophilic groups) eliminates the need for a diluent in the polymerizable composition. Non-limiting examples of these and other components that may be included in the polymerizable composition are provided in U.S. Patent No. 8,231,218.

[0095] Non-limiting examples of usable polysiloxane hydrogels include comfilcon A, fanfilcon A, senofilcon A, senofilcon C, somofilcon A, narafilcon A, delefilcon A, lotrafilcon A, lotrafilcon B, balafilcon A, samfilcon A, galyfilcon A, and asmofilcon A.

[0096] A specific example of the hydrogel contact lens of the present invention is a contact lens based on a polymerizable composition comprising 25% to 55% by weight of a siloxane monomer or macromonomer, 30% to 55% by weight of a vinyl monomer selected from NVP, VMA, or combinations thereof, and optionally about 1% to about 20% by weight of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof, and optionally about 1% to about 20% by weight of a hydrophobic monomer selected from methyl methacrylate (MMA), isoborneol methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof. Polysiloxane hydrogel materials made from this specific embodiment of the polymerizable composition include Stefano A, Canfilcon A, Shamofac A, Vanfilcon A, and Enfilcon A. In another example, the polymerizable composition described above comprises a siloxane of StefanoA, specifically a first siloxane having a structure represented by formula (II).

[0097]

[0098] and a second siloxane having a structure represented by formula (III),

[0099]

[0100] Conventional methods can be used to manufacture the contact lenses of the present invention. As an example, a polymerizable composition for a hydrogel composition is dispensed into a master mold member having a concave surface defining the anterior surface of a contact lens. A male mold member having a convex surface defining the back surface (i.e., the corneal contact surface) of the contact lens is combined with the master mold member to form a contact lens mold assembly, which is then subjected to curing conditions (e.g., UV or thermal curing conditions) under which the curable composition is formed into a polymeric eyepiece body. The master and male mold members can be non-polar or polar molds. The mold assembly is disassembled (i.e., demolded) and the polymeric eyepiece body is removed from the mold and contacted with a solvent (e.g., an organic solvent, such as ethanol) to extract unreacted components from the eyepiece body. After extraction, the eyepiece body is hydrated in one or more hydrating liquids (e.g., water or an aqueous solution) and packaged. An exemplary method for manufacturing polysiloxane hydrogel contact lenses is described in U.S. Patent No. 8,865,789.

[0101] The glycerophospholipids are typically loaded into the polymer eyeglasses during the extraction step. Generally, after curing, the polymer eyeglass body swells in an extraction solvent (e.g., ethanol) containing the glycerophospholipids. When the extracted polymer eyeglass body is subsequently placed in a hydration solution (e.g., deionized (DI) water), the extraction solvent is removed, and the glycerophospholipids remain associated with the polymer eyeglass body.

[0102] Examples of extraction solvents and hydration liquids used in extraction and hydration processes may consist of denatured ethanol, a 50 / 50 (by volume) mixture of denatured ethanol and deionized water, and deionized water. As an example, the extraction and hydration process may involve at least one extraction step in denatured ethanol followed by a 50:50 ethanol-water mixture, followed by at least one hydration step in deionized water, wherein each extraction and hydration step may be sustained at a temperature of about 20°C to about 30°C for about 15 minutes to about 3 hours. An extraction solvent may contain 2-oleoylphospholipids to enable the loading of said 2-oleoylphospholipids onto the polymer eyeglass body.

[0103] Any extraction solvent used as the loading solution for the glycerophospholipids may contain glycerophospholipids at a concentration of 1 to 50 mg / mL, for example, 2 to 20 mg / mL. This concentration may be at least 1 mg / mL, at least 3 mg / mL, at least 5 mg / mL, or at least 10 mg / mL. In one example, the concentration of glycerophospholipids in the extraction solvent is about 2 to about 20 mg / mL, for example, 3 to 10 mg / mL. The amount of glycerophospholipids loaded onto the polymer eyeglass body may be from 1 μg to 1000 μg. The amount of glycerophospholipids loaded onto the polymer eyeglass body may be at least 100 μg, at least 200 μg, or at least 500 μg. Preferably, the amount of glycerophospholipids loaded onto the polymer eyeglass body is at least 300 μg, for example, from 300 μg to 1000 μg.

[0104] In some instances, the glycerophospholipids, once loaded onto the polymer eyeglass body, are stable and do not substantially release or degrade from the polymer eyeglass body during the vaporization process of a sealed contact lens package containing unworn hydrogel contact lenses in a packaging solution, or during storage of the packaging solution. Therefore, the packaging solution impregnating the contact lenses releases less than 10 ppm of C from the contact lenses before, immediately after, or after 1 day at 25°C, or after 30 days at 25°C, or after 60 days at 25°C, or after 120 days at 25°C. 12 -C 26 Glycerophospholipids with the acyl group at the sn-2 position enter the packaging solution or are released from the contact lens into the packaging solution in amounts less than 5 ppm, less than 1 ppm, or 0 ppm. Advantageously, no more than 20% by weight, especially less than 10% by weight, and preferably less than 5% by weight, of the glycerophospholipids associated with the polymeric lens body are released into the packaging solution after storage at 25°C for at least 1 day. Whether the glycerophospholipids are released from the contact lens during vapor treatment or storage can be determined by testing the presence of the glycerophospholipids in the packaging solution using LCMS or other suitable analytical methods.

[0105] As part of this invention, the contact lenses may be sealed in contact lens packaging. The packaging solution sealed in the contact lens packaging may be any conventional contact lens compatible solution. In one example, the packaging solution comprises, or is substantially comprised of, an aqueous solution of a buffer and / or a tension agent. In another example, the packaging solution contains additional agents, such as one or more additional antimicrobial agents, and / or comfort agents, and / or hydrophilic polymers, and / or surfactants and / or other beneficial agents. In some examples, the packaging solution may contain polysaccharides (e.g., hyaluronic acid, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, etc.) or other high molecular weight polymers, such as polyvinylpyrrolidone, which are commonly used as comfort polymers or thickeners in ophthalmic solutions and contact lens packaging solutions. In other examples, the packaging solution may contain ophthalmic medications. The packaging solution may have a pH in the range of about 6.8 or 7.0 to about 7.8 or 8.0. In one example, the packaging solution contains a phosphate buffer or a borate buffer. In another example, the packaging solution contains a tensioning agent selected from sodium chloride or sorbitol, in an amount that maintains the osmotic pressure in the range of about 200 to 400 mOsm / kg, and typically in the range of about 270 mOsm / kg to about 310 mOsm / kg.

[0106] It should be understood that conventional manufacturing methods can be used to manufacture sealed contact lens packaging. In a method of manufacturing contact lens packaging, the method may include the steps of: placing an unworn contact lens and contact lens packaging solution in a container, placing a cap on the container, and sealing the cap on the container. Generally, the container is configured to receive a single contact lens and a sufficient amount of packaging solution to completely cover the contact lens, typically about 0.5 to 1.5 ml. The container may be made of any suitable material (e.g., glass or plastic). In one example, the container is in the form of a plastic base member comprising multiple threads and a cap comprising a plastic cap member comprising a set of compatible threads for engaging with the threads of the base member, thereby providing a resealable cap. It should be understood that other types of packaging may also be used to provide resealable packaging. For example, the contact lens packaging may comprise a plastic cap comprising features that engage with compatible features of the container to form a tight fit. The method of manufacturing sealed contact lens packaging may further include sterilizing the unworn contact lens by steam treatment of the sealed contact lens packaging. Sealing typically involves subjecting sealed contact lens packaging to a temperature of at least 121°C for at least 20 minutes.

[0107] The contact lens may be unworn (i.e., a new contact lens, not previously used by the patient), immersed in a packaging solution and sealed in a package. The package may be a blister pack, a glass vial, or other suitable container. The package may include a base component having a cavity for holding the packaging solution, a cap forming a liquid-tight seal with the base component, and the unworn contact lens. The sealed package may be sterilized by a sterilizing dose of radiation (including heat or steam), for example by steam treatment or by gamma radiation, electron beam radiation, ultraviolet radiation, etc.

[0108] In one particular instance, the packaged contact lenses were sterilized by steam sterilization.

[0109] The final product may be a sterile, packaged contact lens (e.g., a polysiloxane hydrogel contact lens) with ophthalmologically acceptable surface wettability.

[0110] The release of C described in this article 12 -C 26 Hydrogel contact lenses containing fatty acids can be used to correct vision in symptomatic contact lens wearers. For example, the present invention releases C... 12 -C 26 Fatty acid hydrogel contact lenses can increase the duration of comfortable contact lens wear in symptomatic contact lens wearers. In this article, “symptomatic contact lens wearers” or “symptomatic subjects” refers to those classified as symptomatic contact lens wearers using the CLDEQ-8 as described by Chalmers et al. (see Chalmers et al., Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinions on contact lens performance. Ophthalmology and Vision Science 2012; 89(10):1435-1442.). Compared to control lenses or the habitual lenses of control lens wearers, the release of C described in this article… 12 -C 26 Hydrogel contact lenses containing fatty acids can be worn by contact lens wearers to reduce lens perception and / or result in fewer "lens perception events" during the day. The term "control lenses" mentioned in this article refers to lenses that do not contain phospholipids or C. 12 -C 26 Fatty acids, but in other respects, their release of C 12 -C 26Fatty acid-sensitive contact lenses are the same as those for contact lenses. A reduction in eye perception and / or eye perception events during contact lens wear can be determined using an "eye perception recorder" as described by Read et al. (see Read et al., Monitoring ocular discomfort using a wrist-mounted electronic logger. Contact Lens and Anterior Eye, Vol. 43 (2020) 476-483).

[0111] Example

[0112] The following examples illustrate certain aspects and advantages of the invention, but should not be construed as being limited thereto.

[0113] Example 1. Determination of susceptibility to phospholipid digestion using the sPLA2-IIA test.

[0114] Each phospholipid-loaded eyeglass was removed from its packaging and placed overnight at 125 rpm on a shaker in a 6 mL glass vial containing 5 mL of the ATF described in Example 2 to elute any free fatty acids that may be present in the eyeglasses.

[0115] Before running the digestion test, each eyeglass was rinsed for 30 minutes in a 6 ml glass vial containing 5 mL of fresh aliquots of ATF.

[0116] A 50 ppm solution of sPLA2 was prepared by adding 200 μl of ATF to a tube containing 10 μg of recombinant human PLA2G2A (Creative BioMart, catalog number PLA2G2A-669H). This solution was referred to as ATF+sPLA2. Alternatively, human reflex tears could be used instead of ATF+sPLA2. Two 4 mm lenses were cut from each pair of eyeglasses. One lens from each pair was placed in a tube containing 100 μL of ATF, and the other lens was placed in a tube containing 100 μL of ATF+sPLA2. The tubes were incubated at 35 ± 2 °C for 4 hours without shaking.

[0117] At T=4hr, 50 μl of release medium from each eyepiece was transferred to an HPLC vial, and 500 μl of isopropanol (IPA) was added and thoroughly mixed. An HPLC vial (50 μl ATF + 500 μl IPA) was also prepared at T=0hr. All vials were sonicated for 15 min and centrifuged. The supernatant was removed for LCMS injection.

[0118] The supernatant was injected into an LCMS instrument equipped with an ACQUITY UPLC BEH C18 1.7 μg, 2.1 mm x 15 cm column, running a 65% A to 90% B mobile phase gradient at a flow rate of 0.35 mL / min, where A = 40% acetonitrile aqueous solution containing 10 mM ammonium acetate and 0.2% (v / v) ammonium hydroxide, and B = 10% acetonitrile IPA solution containing 10 mM ammonium acetate and 0.2% (v / v) ammonium hydroxide. The mass spectrometer was operated in negative electrospray mode. Peaks of the specific fatty acid of interest (i.e., fatty acids released from the sn-2 position of the phospholipids in the contact lens) in the supernatant were measured. The ratio of fatty acid peak areas in the ATF with and without sPLA2 was calculated.

[0119] Example 2. sPLA2-mediated phospholipid digestion in Steinfeld A glasses loaded with different phospholipids.

[0120] The phospholipids shown in Table 1 were obtained from Avanti Polar Lipids. A 3 mg / ml loaded solution of the phospholipids shown in Table 1 was prepared by adding 2.4 mL of ethanol to 9 mg of phospholipids, sonicating (up to 14 minutes), then adding 0.6 mL of DI water and sonicating again (up to 15 minutes) to dissolve the phospholipids.

[0121] Table 1.

[0122]

[0123]

[0124] Wash the hydrated contact lenses made of Stefan-Ferric A three times for 30 minutes each time in 3 mL of pure water. Place each washed lens in 3 mL of phospholipid loading solution and incubate at 75 rpm for 3 hours at room temperature with gentle shaking. Then rinse the loaded lenses and hydrate with several DI water exchanges. Pack the lenses in buffered saline contact lens packaging solution and perform a steam treatment.

[0125] Artificial tears (ATF) are prepared by adding the first three ingredients listed in Table 2 to a clean-grade vial and then adding 30 mL of the fourth ingredient.

[0126] Table 2.

[0127]

[0128] Following the steam distillation process, the susceptibility of each eyeglass to phospholipid digestion via sPLA2-IIA was tested using the method described in Example 1. The peak of oleic acid (OA) in the supernatant submitted for LCMS analysis was measured (m / z trace = 281.24). The ratio of OA in ATF with and without sPLA2 was calculated. The results are shown in Table 3.

[0129] Table 3. Oleic acid peak area in ATF with and without sPLA2.

[0130] sample ATF ATF+sPLA2 ratio DOPG 36 9958 279 DOPE 463 2127 4.6 DOPC 102 125 1.2 DOPS 88 1437 16.4

[0131] The results showed that contact lenses loaded with 2-oleoylphosphatidylcholine were less susceptible to sPLA2-mediated degradation and fatty acid release, while contact lenses loaded with phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylserine were less susceptible to sPLA2-mediated fatty acid release.

[0132] Example 3. DOPG Loaded Steinfeld A Contact Lenses

[0133] Sodium 1,2-dioleoyl-sn-glycerol-3-phosphate-rac-(1-glycerol) (DOPG) from Sigma-Aldrich was dissolved in 50 vol% ethanol (EtOH) and 50 vol% deionized water and sonicated until the DOPG was completely dissolved to provide DOPG-loaded solutions in the concentration range of 1 mg / ml to 10 mg / ml.

[0134] Polysiloxane hydrogel contact lenses were prepared by curing a formulation of Stefanocon A in a polypropylene contact lens mold. The cured Stefanocon A was removed from the mold, and each lens was extracted in EtOH to remove unreacted monomers. The lenses were then placed in the DOPG loading solution for approximately 90 minutes and subsequently hydrated with several DI water exchanges. The lenses were packaged in plastic blister packs containing approximately 1.2 ml of a packaging solution containing phosphate-buffered saline (PBS) and subjected to a steam-drying process.

[0135] The amount of DOPG in each pair of glasses was determined by extracting the glasses with isopropanol (IPA) and measuring the DOPG in the extract by LCMS. Simply put, each pair of glasses was removed from its blister packaging, lightly dipped in ink to remove excess packaging solution, and placed in a 20 mL glass vial containing 10 mL of 100% IPA. The vial was then placed on a benchtop shaker at 300 rpm overnight (approximately 16 hours) at room temperature. For Stefanova A, a single 2-hour extraction step is sufficient to extract substantially all DOPG from the glasses. More hydrophobic polysiloxane hydrogel glasses materials may require a second overnight extraction to extract all DOPG; in this case, the IPA from the first extraction step is removed and replaced with 3 mL of fresh IPA, then shaken overnight at 300 rpm at room temperature. The amount of DOPG in the IPA extract from each pair of glasses, relative to a DOPG standard solution, was determined by LCMS. The DOPG loading concentration and average DOPG in each pair of glasses are shown in Table 4.

[0136] Table 4.

[0137] DOPG loading concentration Average DOPG / glasses 1.0 mg / mL 240μg 2.5 mg / mL 495μg 5.0 mg / mL 760μg 7.5mg / ml 895μg 10.0mg / ml 975μg

[0138] Example 4. Determining the fatty acid release curve

[0139] To determine if the load includes C 12 -C 26 Fatty acid release curves for polysiloxane hydrogel contact lenses with acyl phospholipids at the sn-2 position, wherein the lenses were removed from their packaging and placed overnight at 125 rpm on a shaker in a 6 mL glass vial containing 5 mL of ATF (described in Example 1) to elute any free fatty acids that may be present in the lenses.

[0140] Then, at 35°C, each eyepiece was transferred to a 6 mL glass vial containing 3 mL of the ATF+sPLA2 in vitro release medium described in Example 1. Alternatively, phospholipase A2 from bee venom (accession number 9001-84-7) could be used instead of the same concentration (50 ppm) of recombinant human PLA2G2A. The vials were placed in a 35°C incubator on a shaker at 50 rpm in 2-hour increments (e.g., 2hr, 4hr, 6hr, 8hr, and 10hr). 2.5 mL of the in vitro release medium was removed from each vial and submitted for analysis. If the release medium was not analyzed immediately at a specific time point, a sample was collected and mixed with IPA (1:10 v / v ratio) to stop enzymatic activity. Then, 2.5 mL of fresh ATF+sPLA2 in vitro release medium was added back to each vial, and the eyepieces were incubated again. At the end of the release experiment, the amount of fatty acids in the release medium at each time point was analyzed by LCMS using the method described in Example 1.

[0141] Example 5. Oleic acid release from a 5 mg / mL DOPG loaded contact lens (lens A) and a 3 mg / mL DOPG loaded contact lens (lens B).

[0142] Polysiloxane hydrogel contact lenses were prepared using a DOPG loading concentration of 5 mg / mL (lens A) and 3 mg / mL (lens B), as in Example 2. Using the method of Example 4, the oleic acid release rate of lenses A and B was determined using an ATF release medium containing 50 ppm bee venom sPLA2 enzyme (accession number 9001-84-7). Oleic acid release in the in vitro release medium samples was tracked every 2 hours, with lenses A and B as follows: Figure 2 and 3 The results are shown in Table 5, which gives the cumulative oleic acid release at each time point (starting from T=0).

[0143] Table 5.

[0144] time Average cumulative amount of A-OA released from glasses Average cumulative amount of B-OA released from glasses 2h 53.7μg 38.5μg 4hr 101.2μg 75.6μg 6hr 148.3μg 110.4μg 8hr 190.5μg 141.1 μg 10hr 210.3μg 165.8μg

[0145] The results showed that the constant release of oleic acid persisted for at least 10 hours for both glasses A and B. The approximate elution rates of oleic acid from glasses A and B are shown in Table 6.

[0146] Table 6.

[0147] Glasses DOPG loading concentration Average release rate of OA / glasses A 5mg / mL Approximately 22 μg / hr B 3mg / mL Approximately 17 μg / hr

[0148] Example 6. DHA release from SiHy glasses with different DHAPG loads.

[0149] Contact lenses prepared from Stanfecan A and Shamofac A were immersed in 3 mg / mL DHAPG (1,2-bis(docosahexaenoyl)-sn-glycerol-3-[phosphate-rac-(1-glycerol)](sodium salt)) dissolved in 50% ethanol. DHA release from the DHAPG-loaded lenses was tested using the digestion assay of Example 1, except that ATF+sPLA2 reflective tears obtained from a single individual were used.

[0150] Based on the total DHA and DHAPG measured in the digested sample, the DHAPG digested 4 hours later was determined using the following equation.

[0151] Digested DHAPG = (Measured DHA * MW of DHAPG) / (MW of DHA)

[0152] Total DHAPG = Digested DHAPG + Measured DHAPG

[0153] Digestion % = Digested DHAPG / Total DHAPG

[0154] The results are shown in Table 7, indicating that the eyeglass material can affect sPLA2-mediated glycerophospholipid digestibility.

[0155] Table 7.

[0156]

[0157] The disclosure herein refers to certain illustrative examples, and it should be understood that these examples are presented by way of example and not by way of limitation. Although exemplary examples are discussed, the foregoing embodiments are intended to be construed as covering all modifications, substitutions, and equivalents of the examples that may fall within the spirit and scope of the invention as defined by further disclosures.

[0158] The use of terms such as “an instance”, “a specific instance”, “one aspect”, “an embodiment”, or similar phrases herein is intended to introduce the release of this invention. 12 -C 26 Hydrogel contact lenses containing fatty acids or components thereof, sealed contact lens packaging or components thereof, or the manufacture of the present invention for releasing C 12 -C 26One or more features of the method for making fatty acid hydrogel contact lenses (depending on the context) may be combined with any combination of previously described or subsequently described examples, aspects, embodiments (i.e., features), unless such particular combination of features is mutually exclusive, or if the context otherwise indicates. Furthermore, as used herein, the singular forms “a,” “an,” and “described” include multiple indicators (e.g., at least one or more) unless the context clearly indicates otherwise. Thus, for example, references to “contact lenses” include a single lens as well as two or more of the same or different lenses.

[0159] All references cited in this disclosure are incorporated herein by reference in their entirety to the extent that they do not contradict this disclosure.

[0160] This invention may include any combination of various features or embodiments as stated in the preceding sentences and / or paragraphs (including numbered items above) and / or described in the claims below. Any combination of features disclosed herein is considered part of this invention and is not intended to limit the composable features.

[0161] Other embodiments of the invention will become apparent to those skilled in the art from consideration of this specification and practice. This specification and examples are intended to be illustrative only, and the true scope and spirit of the invention are indicated by the following claims and their equivalents.

Claims

1. An unworn polysiloxane hydrogel contact lens sealed in packaging, said contact lens comprising a loading of at least one C at the sn-2 position. 12 -C 26 A polymeric lens body of acyl glycerophospholipids, wherein the glycerophospholipids, when present in the polymeric lens body, are readily digested by secretory phospholipase 2-acyl hydrolase (sPLA2) enzyme found in human tears and / or the polysiloxane hydrogel contact lens releases C upon contact with a solution containing sPLA2-IIA. 12 -C 26 Fatty acids and their salts, of which C 12 -C 26 The fatty acids are the digestion products of the glycerophospholipids; In this process, after immersing identical Stefancon A contact lenses, each loaded with at least 200 µg of the glycerophospholipids, in each release medium for 4 hours at 35°C, C, derived from the digestion of the sn-2 position acyl group, was released into an artificial tear release medium containing the sPLA2 enzyme. 12 -C 26 When the amount of fatty acids released into a control artificial tear release medium that is otherwise identical and lacks phospholipase A2 is at least 3 times that of C12-C26 fatty acids, glycerophospholipids containing C12-C26 acyl groups at the sn-2 position are considered readily digestible by sPLA2 enzyme. When the contact lens is immersed at 35°C in a release medium containing artificial tears with 50 ppm sPLA2-IIA, the contact lens continuously releases at least 0.1 μg / hr for at least 4 hours. 12 -C 26 fatty acid.

2. The contact lens according to claim 1, wherein the glycerophospholipid is of formula (I): Formula (I) Where X is –O– or –O(CO)–, R 1 and R 2 Each independently is C 11-25 Alkyl, and R 3 The radical is selected from hydrogen, C 1-10 Polyols, ethanolamines and serine, or salts of the glycerophospholipids of formula (I).

3. The contact lens according to claim 1, wherein the glycerophospholipid is phosphatidylserine, phosphatidylethanolamine, or phosphatidylglycerol.

4. The contact lens according to claim 1, wherein the hydrogel is neutral or cationic.

5. The contact lens of claim 1, wherein the polymeric lens body is a reaction product comprising a polymerizable composition containing at least one hydrophilic monomer comprising vinyl groups.

6. The contact lens according to claim 1, wherein the polymer lens body comprises a first siloxane having a structure represented by formula (II), Equation (II) The reaction product of a polymerizable composition of a second siloxane having a structure represented by formula (III) Formula (III).

7. The contact lens according to claim 1, wherein the glycerophospholipid is 1,2-dioleoylphosphatidylglycerol, 1-palmitoyl-2-oleoylphosphatidylglycerol, 1-stearoyl-2-oleoyl or 1,2-bis(docosahexaenoyl)phosphatidylglycerol.

8. The contact lens of claim 1, wherein the polymer lens body is loaded with an amount of glycerophospholipids from 1 μg to 1000 μg.

9. The contact lens of claim 1, wherein the polymer lens body is loaded with an amount of glycerophospholipids ranging from 25 μg to 1000 μg.

10. The contact lens of claim 1, wherein the polymer lens body is loaded with an amount of glycerophospholipids ranging from 300 μg to 1000 μg.

11. The contact lens of claim 1, wherein when the contact lens is immersed at 35°C in a release medium comprising artificial tears containing 50 ppm sPLA2-IIA, the contact lens continuously releases at least 0.5 μg / hr for at least 8 hours. 12 -C 26 fatty acid.

12. The contact lens of claim 1, wherein when the contact lens is immersed at 35°C in a release medium comprising artificial tears containing 50 ppm sPLA2-IIA, the contact lens continuously releases at least 0.5 μg / hr for at least 10 hours. 12 -C 26 fatty acid.

13. The contact lens according to claim 1, wherein the glycerophospholipid is of formula (I): Formula (I) Where X is –O– or –O(CO)–, R 1 and R 2 Each independently is C 13-21 Alkyl, and R 3 The radical is selected from hydrogen, C 1-10 Polyols, ethanolamines and serine, or salts of the glycerophospholipids of formula (I).

14. The contact lens of claim 1, wherein the packaging comprises: (a) A base component having a cavity for containing a packaged solution; and (b) A cover, which forms a liquid-tight seal with the base component.

15. A method for manufacturing a polysiloxane hydrogel contact lens comprising a polymer lens body loaded with glycerophospholipids, wherein the glycerophospholipids contain C at the sn-2 position. 12 -C 26 Acyl glycerophospholipids, wherein the glycerophospholipids, when present in the polymer lens body, are readily digested by secretory phospholipase 2-acyl hydrolase (sPLA2) enzyme found in human tears and / or the polysiloxane hydrogel contact lens releases C upon contact with a solution containing sPLA2-IIA. 12 -C 26 Fatty acids and their salts, C 12 -C 26 The fatty acids are the digestion products of the glycerophospholipids. The method includes: a) Polymerize the polymerizable composition in a contact lens mold to obtain the polymeric eyeglass body; b) Remove the polymeric eyeglass body from the contact lens mold; c) Place the polymeric eyeglass body in a container containing C at the sn-2 position. 12 -C 26 The process involves: d) extraction of the acyl glycerophospholipid in an organic solvent; e) hydration of the polymer eyeglass body in an aqueous liquid to obtain the hydrogel contact lens; f) sealing the hydrogel contact lens in a package with a packaging solution; and optionally, f) vapor-treating the package. In this process, after immersing identical Stefancon A contact lenses, each loaded with at least 200 µg of the glycerophospholipids, in each release medium for 4 hours at 35°C, C, derived from the digestion of the sn-2 position acyl group, was released into an artificial tear release medium containing the sPLA2 enzyme. 12 -C 26 When the amount of fatty acids released into a control artificial tear release medium that is otherwise identical and lacks phospholipase A2 is at least 3 times that of C12-C26 fatty acids, glycerophospholipids containing C12-C26 acyl groups at the sn-2 position are considered readily digestible by sPLA2 enzyme. When the contact lens is immersed at 35°C in a release medium containing artificial tears with 50 ppm sPLA2-IIA, the contact lens continuously releases at least 0.1 μg / hr for at least 4 hours. 12 -C 26 fatty acid.

16. A certain amount containing C 12 -C 26 The use of glycerophospholipids with the acyl group at the sn-2 position for enhancing the comfort of polysiloxane hydrogel contact lenses, wherein the phospholipid is associated with the polymeric lens body of the polysiloxane hydrogel contact lens, and wherein the glycerophospholipid, when present in the polymeric lens body, is readily digested by secretory phospholipase 2-acylhydrolase (sPLA2) enzyme found in human tears and / or the polysiloxane hydrogel contact lens releases C upon contact with a solution containing sPLA2-IIA. 12 -C 26 Fatty acids and their salts, C 12 -C 26 The fatty acids are the digestion products of the glycerophospholipids; In this process, after immersing identical Stefancon A contact lenses, each loaded with at least 200 µg of the glycerophospholipids, in each release medium for 4 hours at 35°C, C, derived from the digestion of the sn-2 position acyl group, was released into an artificial tear release medium containing the sPLA2 enzyme. 12 -C 26 When the amount of fatty acids released into a control artificial tear release medium that is otherwise identical and lacks phospholipase A2 is at least 3 times that of C12-C26 fatty acids, glycerophospholipids containing C12-C26 acyl groups at the sn-2 position are considered readily digestible by sPLA2 enzyme. When the contact lens is immersed at 35°C in a release medium containing artificial tears with 50 ppm sPLA2-IIA, the contact lens continuously releases at least 0.1 μg / hr for at least 4 hours. 12 -C 26 fatty acid.

17. The use according to claim 16, wherein the polysiloxane hydrogel contact lens comprises C loaded at the sn-2 position. 12 -C 26 The polymeric lens body of acyl glycerophospholipids.

18. The use according to claim 16, wherein the perception of the contact lens is reduced in the contact lens wearer, thereby enhancing the comfort of the contact lens in symptomatic contact lens wearers and / or increasing the duration of comfortable contact lens wear time in symptomatic contact lens wearers.

19. A polysiloxane hydrogel composition for reducing lens perception in contact lens wearers, thereby enhancing the comfort of the contact lens in the wearer and / or increasing the duration of comfortable contact lens wear in the wearer, the composition comprising (a) a polymeric lens body of a reaction product polymerizable by the composition, the polymeric lens body being loaded with (b) a certain amount of C contained at the sn-2 position. 12 -C 26 Acyl glycerophospholipids, wherein the glycerophospholipids, when present in the polymer lens body, are readily digested by secretory phospholipase 2-acyl hydrolase (sPLA2) enzyme found in human tears and / or the polysiloxane hydrogel contact lens releases C upon contact with a solution containing sPLA2-IIA. 12 -C 26 Fatty acids and their salts, of which C 12 -C 26 The fatty acids are the digestion products of the glycerophospholipids; In this process, after immersing identical Stefancon A contact lenses, each loaded with at least 200 µg of the glycerophospholipids, in each release medium for 4 hours at 35°C, C, derived from the digestion of the sn-2 position acyl group, was released into an artificial tear release medium containing the sPLA2 enzyme. 12 -C 26 When the amount of fatty acids released into a control artificial tear release medium that is otherwise identical and lacks phospholipase A2 is at least 3 times that of C12-C26 fatty acids, glycerophospholipids containing C12-C26 acyl groups at the sn-2 position are considered readily digestible by sPLA2 enzyme. When the contact lens is immersed at 35°C in a release medium containing artificial tears with 50 ppm sPLA2-IIA, the contact lens continuously releases at least 0.1 μg / hr for at least 4 hours. 12 -C 26 fatty acid.

20. The composition of claim 19, wherein the composition is in the form of a contact lens and comprises a C-containing element at the sn-2 position. 12 -C 26 The polymeric lens body of acyl glycerophospholipids.

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