Polyvinyl alcohol-containing elastomer matrix

Abstract

The present invention relates to a shaped polyvinyl alcohol (PVOH)-based elastomer matrix for ophthalmic applications, and more specifically, to such a matrix that is biodegradable, but is not limited thereto.

Description

Technical Field

[0001] [Related Applications] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 462,269, filed Apr. 27, 2023, and U.S. Provisional Patent Application No. 63 / 463,034, filed Apr. 30, 2023. The entire contents of this U.S. application are hereby incorporated by reference and made a part of this specification.

[0002] The present invention, in some embodiments, relates to a shaped polyvinyl alcohol (PVOH)-based elastomeric matrix for ophthalmic applications, and more particularly, but not limited to, such a matrix that is biodegradable or bioerodible.

Background Art

[0003] Polyvinyl alcohol (PVOH) is a water-soluble synthetic polymer represented by the formula (C2H4O)n. PVOH is prepared by the hydrolysis of polyvinyl acetate, which replaces acetate groups with hydroxyl groups. PVOH has numerous applications, including biomedical and pharmaceutical applications such as the inner walls of artificial hearts, artificial cartilage, catheters, skin, and membranes for the pancreas. PVOH can be crosslinked chemically or physically (i.e., without covalent bonds).

[0004] During physical crosslinking, hydroxyl groups interact to form intramolecular and intermolecular hydrogen bonds, resulting in the formation of crystallites. Physical crosslinking is typically carried out by freeze-thaw cycles with or without solvent addition, yielding well-known cryogels. Alternatively, a solution of polyvinyl alcohol can be dried (Otsuka, E., & Suzuki, A., Journal of Applied Polymer Science, 2009, 114(1), 10-16, doi:10.1002 / app.30546). Various plasticizers can be added to improve flexibility, and the amount added is generally less than 30%, often less than 10% (Mohsin, M., et al., Journal of Applied Polymer Science, 2011, 122(5), 3102-3109. doi:10.1002 / app.34229, Lim, LY et al., Drug Development and Industrial Pharmacy, 1994, 20(6), 1007-1020. doi:10.3109 / 03639049409038347, and Wu, W. et al., Journal of Polymers and the Environment, 2011, 20(1), 63-69. doi:10.1007 / s10924-011-0364-7).

[0005] Zhang, B. et al., (Ceramics International, 2020, doi:10.1016 / j.ceramint.2020.03.286) teaches the beneficial role of the mechanical properties of polyvinyl alcohol film in the YSZ tape calendering process.

[0006] U.S. Patent No. 4,874,562 discloses a method for molding polyvinyl alcohol contact lenses.

[0007] U.S. Patent No. 4,663,358 discloses a porous, transparent hydrated gel prepared from a poly(vinyl alcohol) solution in a mixed solvent comprising water and a water-miscible organic solvent.

[0008] U.S. Patent No. 10,513,588 discloses a water-soluble polyvinyl alcohol film containing a plasticizer blend.

[0009] U.S. Patent No. 9,724,230 discloses a device and method for treating dry eye, which generally includes a patch or strip applied to the skin of the upper and / or lower eyelid.

[0010] U.S. Patent No. 5,137,728 discloses an intraocular insert for use behind the eyelid, comprising a substantially circular disc having a concave posterior surface and a convex anterior surface.

[0011] U.S. Patent No. 6,217,896 discloses a conjunctival insert for the local delivery of a drug or lubricant into the conjunctival cavity and onto the surface of the eyeball of a human eye.

[0012] U.S. Patent No. 8,679,078 discloses an ophthalmic device for insertion into the eye, comprising a body having an anterior and a posterior surface for placement on one of the episclera and inferiorsclera of the eye.

[0013] U.S. Patent No. 3,416,530 discloses a drug delivery tablet for the human eye, comprising a body made of a flexible material with an uneven cross-section, for insertion into the fornix of the conjunctiva.

[0014] U.S. Patent No. 3,828,777 discloses an ophthalmic device for controlled continuous delivery of a drug to the eye, comprising a body of a microporous drug-release rate-controlling material that is insoluble in tears.

[0015] U.S. Patent No. 4,014,335 discloses an ophthalmic drug delivery device for administering a drug to the eye at a controlled, continuous unit dosing rate to produce a local or systemic physiological or pharmacological effect.

[0016] U.S. Patent No. 5,773,021 discloses a bioadhesive ophthalmic insert for long-term controlled release of a pharmaceutical substance. The insert comprises a composite polymer material matrix into which the pharmaceutical substance is incorporated.

[0017] U.S. Patent No. 10,010,502 discloses a non-degradable topical ophthalmic drug delivery device containing approximately 0.001% w / w to approximately 10% w / w of at least one myopia inhibitor complexed with an iodine in a cross-linked polymer matrix.

[0018] International Publication No. 2022 / 016268 discloses a biocompatible polyvinyl alcohol (PVA) matrix comprising a blend of PVAs of different degrees of hydrolysis.

[0019] U.S. Patent Application Publication No. 2022 / 0168142 discloses an implantable bio-invasive insert for delivering a pharmaceutical active ingredient to the eye.

[0020] U.S. Patent Application Publication No. 2017 / 0226298 discloses a water-soluble film comprising a polyvinyl alcohol (PVOH) resin blend and optionally one or more additional components such as plasticizers, fillers, surfactants, and other additives. [Overview of the project]

[0021] The following is a non-exclusive list containing some examples of embodiments of the present invention. The present invention also includes embodiments containing fewer features than all features in one example, and embodiments using features from multiple examples (even if not expressly described below).

[0022] Example 1. An ophthalmic device having an elastomer matrix, wherein the elastomer matrix comprises: a. Polyvinyl alcohol (PVOH); and b. One or more organic plasticizers, wherein the ratio of the total mass of the one or more organic plasticizers and PVOH is at least 2:1; and c. Water; and the PVOH comprises two or more types of PVOH that differ from each other in one or both of the degree of hydrolysis (HD) and chain length. An ophthalmic device.

[0023] Example 2. The ophthalmic device according to Example 1, wherein each of the two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix.

[0024] Example 3. The ophthalmic device according to Example 1 or Example 2, wherein the two or more types of PVOH comprise one type having a long chain and being completely hydrolyzed, and a. One having a short chain and being partially hydrolyzed; b. One having a long chain and being partially hydrolyzed; c. One having a short chain and being completely hydrolyzed; and at least one type selected from the above.

[0025] Example 4. a. The short-chain monomer units are 200 to 2,000; b. The long-chain monomer units are 2,200 to 5,000; c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or more, and d. The degree of hydrolysis of the partially hydrolyzed PVOH is 95% or less. The ophthalmic device according to any one of Examples 1 to 3.

[0026] Example 5. The ophthalmic device according to any one of Examples 1 to 4, wherein the PVOH comprises two or more types of PVOH having different degrees of hydrolysis (HD).

[0027] An ophthalmic device according to any one of Examples 1 to 5, wherein the difference in chain length between the two types of PVOH is at least 1,000, and they have similar degrees of hydrolysis, with each degree of hydrolysis being between 97% and 100%.

[0028] An ophthalmic device according to any one of Examples 1 to 6, wherein the first of two or more types has a degree of hydrolysis of 97% to 100%.

[0029] An ophthalmic device according to any one of Examples 1 to 7, wherein the second of two or more types has a degree of hydrolysis of less than 93%.

[0030] An ophthalmic device according to any one of Examples 1 to 8, wherein the second of two or more types has a degree of hydrolysis of 80% to 93%.

[0031] Example 10. An ophthalmic device according to any one of Examples 1 to 9, wherein the first of two or more types has a chain length of more than 2,500 units.

[0032] Example 11. An ophthalmic device according to any one of Examples 1 to 10, wherein the second of two or more types has a chain length of less than 1,500 units.

[0033] An ophthalmic device according to any one of Examples 1 to 11, wherein the relationship between the first type of PVOH and the second type of PVOH out of two or more types is approximately 3:1 to approximately 1:3.

[0034] An ophthalmic device according to any one of Examples 1 to 12, wherein the first of two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

[0035] Example 14. An ophthalmic device as described in any one of Examples 1-13, wherein the second type of PVOH accounts for more than 50% of the PVOH.

[0036] Example 15. An ophthalmic device according to any one of Examples 1 to 14, wherein at least two types of PVOH determine the degradation rate of the ophthalmic device.

[0037] Example 16. An ophthalmic device according to any one of Examples 1 to 15, wherein the decomposition rate includes the rate at which a predetermined change occurs in a predetermined mechanical property in artificial tear fluid (STF).

[0038] Example 17. An ophthalmic device according to any one of Examples 1 to 16, wherein the total mass content of PVOH and one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding water.

[0039] Example 18. An ophthalmic device according to any one of Examples 1 to 17, characterized by the elastomer matrix exhibiting substantially isotropic swelling when immersed in simulated tear fluid for 5 minutes at room temperature.

[0040] Example 19. An ophthalmic device according to any one of Examples 1 to 18, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

[0041] Example 20. An ophthalmic device according to any one of Examples 1 to 19, wherein water accounts for less than 50 wt% of the total mass content of the matrix.

[0042] Example 21. An ophthalmic device according to any one of Examples 1 to 20, substantially free from covalent crosslinking.

[0043] Example 22. An ophthalmic device according to any one of Examples 1 to 21, further comprising a pharmaceutically active substance.

[0044] Example 23. An ophthalmic device according to any one of Examples 1 to 22, wherein the elastomer matrix contains a pharmaceutically active substance.

[0045] Example 24. An ophthalmic device according to any one of Examples 1 to 23, wherein the ophthalmic device consists of ophthalmologically acceptable components.

[0046] Example 25. An ophthalmic device according to any one of Examples 1 to 24, wherein at least 90% (w / w) of the plasticizer is an ophthalmic lubricant.

[0047] Example 26. An ophthalmic device as described in any one of Examples 1 to 25, wherein the device weighs 1 mg to 50 mg or 1 mg to 30 mg.

[0048] Example 27. An ophthalmic device according to any one of Examples 1 to 28, wherein the ophthalmic device is configured to be placed on the surface of the eye.

[0049] Example 28. An ophthalmic device according to any one of Examples 1 to 27, wherein the surface of the eye is outside the cornea of ​​the eye and at least partially below only one of the upper or lower eyelids.

[0050] Example 29. An ophthalmic device according to any one of Examples 1 to 28, wherein the device is configured to be attached away from the fornix.

[0051] An ophthalmic device according to any one of Examples 1 to 29, configured to deliver at least one pharmaceutically active substance to the surface of the eye over a period of 5 minutes to 24 hours.

[0052] Example 31. An ophthalmic device according to any one of Examples 1 to 30, which is located between the eyeball and the eyelid and is configured to move with the eyelid when the eyelid moves relative to the eyeball.

[0053] Example 32. An ophthalmic device according to any one of Examples 1 to 31, which is located between the eyeball and the eyelid and is configured to remain on the eyelid side when the eyeball moves relative to the eyelid.

[0054] Example 33. a. The posterior surface adjacent to the ocular surface when in use, b. The front surface that defines the height from the rear, It has, An ophthalmic device according to any one of Examples 1 to 32, wherein two of the heights, separated by a maximum distance of 1 mm from each other, differ from each other by at least 1 mm.

[0055] Example 34. a. Rear and, b. When an ophthalmic device is placed on a plane in a relaxed configuration with its rear surface adjacent to the plane, the front surface defines the height from the plane, It has, An ophthalmic device according to any one of Examples 1 to 32, wherein two of the heights, separated by a maximum distance of 1 mm from each other, differ from each other by at least 1 mm.

[0056] Example 35. a. The posterior surface adjacent to the ocular surface when the ophthalmic device is attached, b. The front surface that defines the height from the rear, It has, An ophthalmic device according to any one of Examples 1 to 32, wherein each of two points on the front surface, spaced at least 1 mm apart from each other along the front surface, has an inclination of at least 45° with respect to the ocular surface.

[0057] Example 36. a. Rear and, b. When an ophthalmic device is placed on a plane in a relaxed configuration with its rear surface adjacent to the plane, the front surface defines the height from the plane, It has, An ophthalmic device according to any one of Examples 1 to 32, wherein two points on the front surface are spaced at least 1 mm apart from each other along the front surface, and each point is inclined at least 45° with respect to the plane.

[0058] Example 37. An ophthalmic device configured to be located between the ocular surface and the eyelid, a. The body comprises an elastomer matrix containing water, one or more types of PVOH, and one or more organic plasticizers, and the body is i. The posterior surface adjacent to the ocular surface when an ophthalmic device is attached, ii. The anterior surface adjacent to the eyelid that covers the surface of the eye when an ophthalmic device is attached, iii. A retaining portion defined between a part of the front and a part of the rear, Characterized by, An ophthalmic device having a retaining portion with a rim structured to move with the eyelid when the eyelid moves relative to the eyeball.

[0059] Example 38. The ophthalmic device according to Example 37, wherein the rim is structured by an inclination of the anterior surface extending from the posterior surface, and the inclination is characterized by an angle greater than 45° between the posterior and anterior surfaces.

[0060] Example 39. An ophthalmic device according to Example 37 or Example 38, configured to be completely located between the ocular surface and the eyelid.

[0061] An ophthalmic device according to any one of Examples 37-39, wherein the inclination exceeding 45 degrees is at least 1 mm in length.

[0062] Example 41. An ophthalmic device according to any one of Examples 37-40, wherein the angle of the inclination of the front surface extending from the rear surface is between 45 and 90 degrees.

[0063] Example 42. An ophthalmic device according to any one of Examples 37 to 41, wherein the retaining portion has a maximum height of 0.5 mm to 5 mm.

[0064] Example 43. An ophthalmic device as described in any one of Examples 37 to 42, wherein the ophthalmic device has a length of approximately 3 mm to approximately 10 mm.

[0065] Example 44. An ophthalmic device as described in any one of Examples 37 to 43, wherein the ophthalmic device has a width of approximately 3 mm to approximately 10 mm.

[0066] Example 45. An ophthalmic device as described in any one of Examples 37-44, wherein the relationship between the width and length of the ophthalmic device is approximately 1:1 to approximately 1:3.

[0067] An ophthalmic device according to any one of Examples 37 to 45, wherein the ratio of the total mass of one or more organic plasticizers and one or more PVOHs is at least 2:1.

[0068] Example 47. An ophthalmic device according to any one of Examples 37 to 46, wherein the main body swells isotropically when exposed to humid conditions.

[0069] Example 48. An ophthalmic device according to any one of Examples 37 to 47, wherein the PVOH comprises two or more types of PVOH that differ from each other in terms of degree of hydrolysis (HD) and / or chain length.

[0070] Example 49. Two or more types of PVOH, one of which has a long chain and is completely hydrolyzed, a. Having short chains and being partially hydrolyzed, b. Having long chains and being partially hydrolyzed, c. Having a short chain and being completely hydrolyzed, An ophthalmic device according to any one of Examples 37 to 48, comprising one of which is at least one of the following.

[0071] Example 50. a. The short chain monomer units are 200 to 2,000. b. The long chain monomer units are 2,200 to 5,000. c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or higher, and d. The degree of hydrolysis of partially hydrolyzed PVOH is 95% or less. An ophthalmic device as described in any one of Examples 37-49.

[0072] Example 51. An ophthalmic device according to any one of Examples 37 to 50, wherein the PVOH comprises two or more types of PVOH having different degrees of hydrolysis (HD).

[0073] An ophthalmic device according to any one of Examples 37 to 51, wherein the chain length difference of the two types of PVOH is at least 1,000 and they have similar degrees of hydrolysis, with each degree of hydrolysis being 97% to 100%.

[0074] An ophthalmic device according to any one of Examples 37 to 52, wherein the first of two or more types has a degree of hydrolysis of 97% to 100%.

[0075] An ophthalmic device according to any one of Examples 37 to 53, wherein the second of two or more types has a degree of hydrolysis of less than 93%.

[0076] An ophthalmic device according to any one of Examples 37 to 54, wherein the second of two or more types has a degree of hydrolysis of 80% to 93%.

[0077] Example 56. An ophthalmic device according to any one of Examples 37 to 55, wherein the first of two or more types has a chain length of more than 2,500 units.

[0078] Example 57. An ophthalmic device according to any one of Examples 37 to 56, wherein the second of two or more types has a chain length of less than 1,500 units.

[0079] An ophthalmic device according to any one of Examples 37 to 57, wherein the relationship between the first type of PVOH and the second type of PVOH out of two or more types is approximately 3:1 to approximately 1:3.

[0080] An ophthalmic device according to any one of Examples 37 to 58, wherein the first of two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

[0081] Example 60. An ophthalmic device according to any one of Examples 37-59, wherein the second type of PVOH accounts for more than 50% of the PVOH.

[0082] Example 61. An ophthalmic device according to any one of Examples 37-60, wherein at least two types of PVOH determine the degradation rate of the ophthalmic device.

[0083] Example 62. An ophthalmic device according to any one of Examples 37 to 61, wherein the decomposition rate includes the rate at which a predetermined change occurs in a predetermined mechanical property in artificial tear fluid (STF).

[0084] Example 63. An ophthalmic device according to any one of Examples 37 to 62, wherein the total mass content of PVOH and one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding water.

[0085] Example 64. An ophthalmic device according to any one of Examples 37-63, characterized by the elastomer matrix exhibiting substantially isotropic swelling when immersed in simulated tear fluid for 5 minutes at room temperature.

[0086] Example 65. An ophthalmic device according to any one of Examples 37-64, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

[0087] Example 66. An ophthalmic device according to any one of Examples 37-65, wherein water accounts for less than 50 wt% of the total mass content of the matrix.

[0088] Example 67. An ophthalmic device according to any one of Examples 37-66, substantially free from covalent crosslinking.

[0089] Example 68. An ophthalmic device according to any one of Examples 37 to 67, further comprising at least one ophthalmologically acceptable pharmaceutically active ingredient.

[0090] Example 69. An ophthalmic device according to any one of Examples 37-68, wherein at least one ophthalmologically acceptable pharmaceutically active ingredient is supported on an elastomer matrix.

[0091] Example 70. An ophthalmic device according to any one of Examples 37-69, wherein at least one ophthalmologically acceptable pharmaceutically active ingredient is dispersed within an elastomer matrix.

[0092] Example 71. An ophthalmic device according to any one of Examples 37-70, wherein at least one ophthalmologically acceptable pharmaceutically active ingredient is encapsulated and then supported by an elastomer matrix.

[0093] Example 72. An ophthalmic device according to any one of Examples 37-71, wherein water constitutes 5 wt% to 50 wt% of the elastomer matrix.

[0094] Example 73. An ophthalmic device according to any one of Examples 37-72, wherein the ophthalmic device is configured to exhibit a weight increase of 50% or less when immersed in simulated tear fluid for 5 minutes.

[0095] Example 74. An ophthalmic device according to any one of Examples 37 to 73, wherein the ophthalmic device is obtained without freezing from a liquid solution containing water, a pharmaceutical active ingredient, PVOH, and an organic plasticizer.

[0096] Example 75. An ophthalmic device according to any one of Examples 37 to 74, wherein the ophthalmic device is obtained without freezing from a liquid solution containing water, a pharmaceutical active ingredient, PVOH, and a water-soluble organic liquid.

[0097] Example 76. An ophthalmic device according to any one of Examples 37 to 75, characterized by having a Young's modulus of 0.05 MPa to 10 MPa.

[0098] Example 77. An ophthalmic device according to any one of Examples 37 to 76, wherein the ophthalmic device is stable for at least 3 months at 25°C ± 2°C and a relative humidity of 60% ± 5%.

[0099] Example 78. An ophthalmic device according to any one of Examples 37 to 77, comprising two or more PVOHs with different degrees of hydrolysis.

[0100] An ophthalmic device according to any one of Examples 37-78, wherein the ratio of two or more types of PVOH is such that the ophthalmic device decomposes by at least 50% of its weight within 24 hours under wet conditions.

[0101] An ophthalmic device according to any one of Examples 37-79, wherein the ratio of two or more types of PVOH is such that the ophthalmic device maintains its original shape under moist conditions for the first 10 minutes.

[0102] Example 81. An ophthalmic device as described in any one of Examples 37-80, which is visible to the naked eye against the conjunctiva of the eye.

[0103] Example 82. An ophthalmic device according to any one of Examples 37 to 81, wherein the retaining portion is defined by the height between the rear surface and the front surface, and the first height, measured from a first point on the rear surface to a corresponding point on the front surface, differs by at least 1 mm from the second height, measured from a second point on the rear surface to a corresponding point on the front surface, and the second point is up to 1 mm away from the first point.

[0104] Example 83. An ophthalmic device according to any one of Examples 37-82, wherein the device is configured to be attached away from the fornix.

[0105] Example 84. An ophthalmic device configured to be located between the ocular surface and the eyelid, comprising a body made from an elastomer matrix containing water, one or more types of PVOH and one or more types of organic plasticizers, The main unit is i. The posterior surface adjacent to the ocular surface when an ophthalmic device is attached, ii. The anterior surface adjacent to the eyelid that covers the surface of the eye when an ophthalmic device is attached, iii. A retaining portion defined between a part of the front and a part of the rear, Characterized by, An ophthalmic device in which the ratio of the total mass of one or more organic plasticizers and one or more PVOHs is at least 2:1.

[0106] Example 85. An ophthalmic device configured to be located between the ocular surface and the eyelid, comprising a body made from an elastomer matrix containing water, one or more types of PVOH and one or more types of organic plasticizers, The main unit is i. The posterior surface adjacent to the ocular surface when an ophthalmic device is attached, ii. The anterior surface adjacent to the eyelid that covers the surface of the eye when an ophthalmic device is attached, iii. A retaining portion defined between a part of the front and a part of the rear, Characterized by, An ophthalmic device in which the ratio of one or more organic plasticizers to one or more PVOHs is such that the device swells by less than 50% (v / v) when left standing in simulated tear solution at room temperature for 15 minutes.

[0107] Example 86. An ophthalmic device according to Example 84 or Example 85, wherein the retaining portion is configured to move the ophthalmic device with the eyelid when the eyelid moves relative to the eyeball.

[0108] Example 87. An ophthalmic device according to any one of Examples 84-86, wherein the angle of the inclination of the anterior surface extending from the posterior surface is greater than 45 degrees.

[0109] Example 88. An ophthalmic device according to any one of Examples 84-87, wherein the angle of the inclination of the front surface extending from the rear surface is between 45 and 90 degrees.

[0110] Example 89. An ophthalmic device according to any one of Examples 84 to 88, wherein the retaining portion has a maximum height of 0.5 mm to 5 mm.

[0111] Example 90. An ophthalmic device as described in any one of Examples 84 to 89, wherein the ophthalmic device has a length of approximately 3 mm to approximately 10 mm.

[0112] Example 91. An ophthalmic device as described in any one of Examples 84 to 90, wherein the ophthalmic device has a width of approximately 3 mm to approximately 10 mm.

[0113] Example 92. An ophthalmic device according to any one of Examples 84 to 91, wherein the relationship between the width and length of the ophthalmic device is approximately 1:1 to approximately 1:3.

[0114] Example 93. An ophthalmic device as described in any one of Examples 84-92, characterized by having an oval shape.

[0115] Example 94. An ophthalmic device according to any one of Examples 84-93, characterized by having a circular body.

[0116] Example 95. An ophthalmic device according to any one of Examples 84 to 94, characterized by having a dome-shaped body.

[0117] Example 96. An ophthalmic device according to any one of Examples 84-95, characterized by having a semi-ellipsoidal shape.

[0118] Example 97. An ophthalmic device according to any one of Examples 84 to 96, wherein the main body swells isotropically when exposed to humid conditions.

[0119] Example 98. An ophthalmic device according to any one of Examples 84 to 97, wherein the PVOH comprises two or more types of PVOH that differ from each other in either degree of hydrolysis (HD) or chain length.

[0120] An ophthalmic device according to any one of Examples 84-98, wherein each of two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix.

[0121] Example 100. Two or more types of PVOH, one of which has a long chain and is completely hydrolyzed, a. Having short chains and being partially hydrolyzed, b. Having long chains and being partially hydrolyzed, c. Having a short chain and being completely hydrolyzed, An ophthalmic device according to any one of Examples 84 to 99, comprising one of at least one of the following.

[0122] Example 101. a. The short chain monomer units are 200 to 2,000. b. The long chain monomer units are 2,200 to 5,000. c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or higher, and d. The degree of hydrolysis of partially hydrolyzed PVOH is 95% or less. An ophthalmic device described in any one of Examples 84-100.

[0123] Example 102. An ophthalmic device according to any one of Examples 84 to 101, wherein the PVOH comprises two or more types of PVOH having different degrees of hydrolysis (HD).

[0124] An ophthalmic device according to any one of Examples 84 to 102, wherein the difference in the lengths of the two PVOH chains is at least 1,000 and they have similar degrees of hydrolysis, all of which are between 97% and 100%.

[0125] Example 104. An ophthalmic device according to any one of Examples 84 to 103, wherein the first of two or more types has a degree of hydrolysis of 97% to 100%.

[0126] Example 105. An ophthalmic device according to any one of Examples 84 to 104, wherein the second of two or more types has a degree of hydrolysis of less than 93%.

[0127] Example 106. An ophthalmic device according to any one of Examples 84 to 105, wherein the second of two or more types has a degree of hydrolysis of 80% to 93%.

[0128] Example 107. An ophthalmic device according to any one of Examples 84 to 106, wherein the first of two or more types has a chain length of more than 2,500 units.

[0129] Example 108. An ophthalmic device according to any one of Examples 84 to 107, wherein the second of two or more types has a chain length of less than 1,500 units.

[0130] An ophthalmic device according to any one of Examples 84 to 108, wherein the relationship between the first type of PVOH and the second type of PVOH out of two or more types is approximately 3:1 to approximately 1:3.

[0131] An ophthalmic device according to any one of Examples 84 to 109, wherein the first of two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

[0132] Example 111. An ophthalmic device as described in any one of Examples 84-110, wherein the second type of PVOH accounts for more than 50% of the PVOH.

[0133] Example 112. An ophthalmic device according to any one of Examples 84-111, wherein at least two types of PVOH determine the degradation rate of the ophthalmic device.

[0134] Example 113. An ophthalmic device according to any one of Examples 84 to 112, wherein the decomposition rate includes the rate at which a predetermined change occurs in a predetermined mechanical property in artificial tear fluid (STF).

[0135] Example 114. An ophthalmic device according to any one of Examples 84 to 113, wherein the total mass content of PVOH and one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding water.

[0136] Example 115. An ophthalmic device according to any one of Examples 84-114, characterized by the elastomer matrix exhibiting substantially isotropic swelling when immersed in simulated tear fluid for 5 minutes at room temperature.

[0137] Example 116. An ophthalmic device according to any one of Examples 84-115, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

[0138] Example 117. An ophthalmic device according to any one of Examples 84-116, wherein water accounts for less than 50 wt% of the total mass content of the matrix.

[0139] Example 118. An ophthalmic device according to any one of Examples 84-117, substantially free from covalent crosslinking.

[0140] Example 119. An ophthalmic device according to any one of Examples 84-118, further comprising at least one ophthalmologically acceptable pharmaceutically active ingredient.

[0141] Example 120. An ophthalmic device according to any one of Examples 84-119, wherein at least one ophthalmologically acceptable pharmaceutically active ingredient is supported by an elastomer matrix.

[0142] Example 121. An ophthalmic device according to any one of Examples 84-120, wherein at least one ophthalmologically acceptable pharmaceutically active ingredient is dispersed within an elastomer matrix.

[0143] Example 122. An ophthalmic device according to any one of Examples 84-121, wherein at least one ophthalmologically acceptable pharmaceutically active ingredient is encapsulated and then supported on an elastomer matrix.

[0144] Example 123. An ophthalmic device according to any one of Examples 84-122, wherein water constitutes 5 wt% to 50 wt% of the elastomer matrix.

[0145] Example 124. An ophthalmic device according to any one of Examples 84 to 123, wherein the ophthalmic device is configured to have a weight increase of 50% or less when exposed to wet conditions.

[0146] Example 125. An ophthalmic device according to any one of Examples 84 to 124, wherein the ophthalmic device is obtained without freezing from a liquid solution containing water, an active ingredient, PVOH, and a water-soluble organic liquid.

[0147] Example 126. An ophthalmic device according to any one of Examples 84 to 125, wherein the ophthalmic device is obtained without freezing from a liquid solution containing water, an active ingredient, PVOH, and a water-soluble organic liquid.

[0148] Example 127. An ophthalmic device according to any one of Examples 84 to 126, characterized by having a Young's modulus of 0.05 MPa to 10 MPa.

[0149] Example 128. An ophthalmic device according to any one of Examples 84-127, wherein the ophthalmic device is stable for at least three months under dry conditions.

[0150] Example 129. An ophthalmic device according to any one of Examples 84 to 128, comprising two or more PVOHs with different degrees of hydrolysis.

[0151] Example 130. An ophthalmic device according to any one of Examples 84 to 129, wherein the ratio between two or more types of PVOH is such that the ophthalmic device disintegrates within 24 hours under wet conditions.

[0152] An ophthalmic device according to any one of Examples 84-130, wherein the ratio between two or more types of PVOH is such that the ophthalmic device maintains its original shape under moist conditions for the first 10 minutes.

[0153] Example 132. An ophthalmic device as described in any one of Examples 84-131, which is visible to the naked eye against the conjunctiva of the eye.

[0154] Example 133. An ophthalmic device according to any one of Examples 84-132, wherein the ophthalmic device is elongated and symmetrical, and all orientations of the device are equivalent as long as the elongated side of the device is in a given direction.

[0155] Example 134. An ophthalmic device according to any one of Examples 84 to 133, wherein the retaining portion is defined by the height between the posterior and anterior surfaces, and a first height, measured from a first point on the posterior surface to a corresponding point on the anterior surface, differs by at least 1 mm from a second height, measured from a second point on the posterior surface to a corresponding point on the anterior surface, and the second point is spaced at most 1 mm from the first point.

[0156] Example 135. An ophthalmic device according to any one of Examples 84-134, configured to be attached away from the fornix.

[0157] Example 136. An ophthalmic device, a. A body containing an elastomer matrix, wherein the elastomer matrix contains 5 wt% to 50 wt% water and at least 50 wt% ophthalmic lubricant, of which 5 wt% to 33 wt% is polyvinyl alcohol (PVOH). The main unit is i. A posterior surface configured to fit the surface of the eye below the eyelid, ii. The front surface that defines the height of the main body from the surface of the eye, iii. A retaining portion defined between a part of the front and a part of the rear, wherein the angle of inclination of the front extending from the rear is greater than 45 degrees, Characterized by the main body, b. A pharmacoactive ingredient (API) for treating ocular conditions, wherein the API is supported on an elastomer matrix and released from the matrix under wet conditions, Includes, An ophthalmic device comprising two or more types of PVOH, each having a different degree of hydrolysis (HD) and / or chain length.

[0158] Example 137. An ophthalmic device according to Example 136, wherein each of two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix.

[0159] Example 138. Two or more types of PVOH, one of which has a long chain and is completely hydrolyzed, a. Having short chains and being partially hydrolyzed, b. Having long chains and being partially hydrolyzed, c. Having a short chain and being completely hydrolyzed, An ophthalmic device according to Example 136 or Example 137, comprising one of at least one of the following.

[0160] Example 139. a. The short chain monomer units are 200 to 2,000. b. The long chain monomer units are 2,200 to 5,000. c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or higher, and d. The degree of hydrolysis of partially hydrolyzed PVOH is 95% or less. An ophthalmic device as described in any one of Examples 136-138.

[0161] Example 140. An ophthalmic device according to any one of Examples 136 to 139, wherein the PVOH comprises two or more PVOHs with different degrees of hydrolysis (HD).

[0162] An ophthalmic device according to any one of Examples 136-140, wherein the chain length difference of the two types of PVOH is at least 1,000 and they have similar degrees of hydrolysis, both of which are 97%-100%.

[0163] An ophthalmic device according to any one of Examples 136 to 141, wherein the first of two or more types has a degree of hydrolysis of 97% to 100%.

[0164] An ophthalmic device according to any one of Examples 136 to 142, wherein the second of two or more types has a degree of hydrolysis of less than 93%.

[0165] An ophthalmic device according to any one of Examples 136 to 143, wherein the second of two or more types has a degree of hydrolysis of 80% to 93%.

[0166] Example 145. An ophthalmic device according to any one of Examples 136 to 144, wherein the first of two or more types has a chain length of more than 2,500 units.

[0167] Example 146. An ophthalmic device according to any one of Examples 136 to 145, wherein the second of two or more types has a chain length of less than 1,500 units.

[0168] An ophthalmic device according to any one of Examples 136 to 146, wherein the relationship between the first type of PVOH and the second type of PVOH out of two or more types is approximately 3:1 to approximately 1:3.

[0169] An ophthalmic device according to any one of Examples 136 to 147, wherein the first of two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

[0170] Example 149. An ophthalmic device as described in any one of Examples 136-148, wherein the second type of PVOH accounts for more than 50% of the PVOH.

[0171] Example 150. An ophthalmic device according to any one of Examples 136-149, wherein at least two types of PVOH determine the degradation rate of the ophthalmic device.

[0172] Example 151. An ophthalmic device according to any one of Examples 136 to 150, wherein the decomposition rate includes the rate at which a predetermined change occurs in a predetermined mechanical property in artificial tear fluid (STF).

[0173] Example 152. An ophthalmic device according to any one of Examples 136 to 151, wherein the total mass content of PVOH and one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding water.

[0174] Example 153. An ophthalmic device according to any one of Examples 136-152, characterized by an elastomer matrix that exhibits substantially isotropic swelling when immersed in simulated tear fluid for 5 minutes at room temperature.

[0175] Example 154. An ophthalmic device according to any one of Examples 136-153, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

[0176] Example 155. An ophthalmic device according to any one of Examples 136-154, wherein water accounts for less than 50 wt% of the total mass content of the matrix.

[0177] Example 156. An ophthalmic device according to any one of Examples 136-155, substantially free from covalent crosslinking.

[0178] Example 157. An ophthalmic device according to any one of Examples 136 to 156, wherein each of the multiple ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

[0179] Example 158. An ophthalmic device according to any one of Examples 136-157, wherein the ophthalmic lubricant contains polyethylene glycol (PEG), and the mass content of PEG in the elastomer matrix is ​​approximately equal to the mass content of PVOH.

[0180] An ophthalmic device according to any one of Examples 136 to 158, wherein at least 35% of the ophthalmologically acceptable lubricant in Example 159 consists of glycerol and propylene glycol.

[0181] Example 160. An ophthalmic device according to any one of Examples 136-159, wherein the API is impregnated into an elastomer matrix.

[0182] Example 161. An ophthalmic device according to any one of Examples 136-160, which can be obtained by mixing the API with water and an ophthalmic lubricant to obtain a mother liquor, and drying the mother liquor at room temperature.

[0183] Example 162. An ophthalmic device according to any one of Examples 136-161, which can obtain the mother liquor without heating it.

[0184] Example 163. An ophthalmic device described in any one of Examples 136-162, which allows the API to be obtained without heating.

[0185] Example 164. The following mechanical properties of an ophthalmic device when under dry conditions: a. Tensile strength of 0.01 MPa to 10 MPa, b. Young's modulus for 0.05 MPa to 10 MPa, and c. Elongation at fracture of 50% to 1,000% An ophthalmic device as described in any one of Examples 136-163, characterized by at least one of the following.

[0186] Example 165. An ophthalmic device according to any one of Examples 136-164, wherein the ophthalmic device is configured to disintegrate within the eye and lose at least 50% of its weight within two hours within the eye.

[0187] Example 166. An ophthalmic device according to any one of Examples 136 to 165, wherein the ophthalmic device is attached and a retaining portion is configured to hold the device in place when the eye rotates.

[0188] Example 167. An ophthalmic device according to any one of Examples 136 to 166, wherein a first height, measured perpendicular to the reference plane from a first point on the posterior surface to a corresponding point on the anterior surface, differs by at least 1 mm from a second height, measured perpendicular to the reference plane from a second point on the posterior surface to a corresponding point on the anterior surface, and the second point is up to 1 mm away from the first point.

[0189] Example 168. An ophthalmic device according to any one of Examples 136-167, having a size and shape such that it is completely covered by the eyelid when placed below the lower eyelid.

[0190] Example 169. An ophthalmic device as described in any one of Examples 136-168, wherein the ophthalmic device is configured for self-administration.

[0191] Example 170. An ophthalmic device according to any one of Examples 136-169, comprising an active ingredient for treating presbyopia.

[0192] Example 171. An ophthalmic device used for the treatment of presbyopia, as described in any one of Examples 136-170.

[0193] Example 172. An ophthalmic device according to any one of Examples 136-171, wherein the body is configured to minimize disturbance to the eyelid when the posterior surface is on the surface of the eye below the eyelid.

[0194] Example 173. An ophthalmic device according to any one of Examples 136-172, wherein the device is configured to be attached away from the fornix.

[0195] Example 174. An ophthalmic pharmaceutical product used for the treatment of presbyopia, a. Elastomer matrix, i. Up to 45 wt% water, ii. At least 50 wt% of an ophthalmic lubricant, An elastomer matrix containing, of which 5 wt% to 33 wt% is polyvinyl alcohol (PVOH), b. Pharmacological drugs for treating presbyopia, Ophthalmic pharmaceutical products, including [specific ingredient / feature].

[0196] Example 175. The ophthalmic pharmaceutical product according to Example 174, wherein the ophthalmic pharmaceutical product is an ophthalmic device described in any one of Examples 1 to 173.

[0197] Example 176. An ophthalmic pharmaceutical product substantially consisting of one or more active pharmaceutical ingredients (APIs), an ophthalmic lubricant, and water, wherein the amount of water is 50 wt% or less of the pharmaceutical product.

[0198] Example 177. The ophthalmic pharmaceutical product according to Example 176, wherein 95 wt% of the ophthalmic pharmaceutical product consists solely of API, an ophthalmic lubricant, and water.

[0199] Example 178. An ophthalmic pharmaceutical product has the following mechanical properties: Tensile strength of 0.01 MPa to 10 MPa, Elastic modulus from 0.05 MPa to 10 MPa, and Elongation at break of 50% to 1,000% An ophthalmic pharmaceutical product as described in Example 176 or Example 177, characterized by at least one of the above.

[0200] Example 179. An ophthalmic pharmaceutical product described in any one of Examples 176 to 178, wherein 3 wt% to 33 wt% of the ophthalmic lubricant consists of PVOH.

[0201] Example 180. An ophthalmic pharmaceutical product according to any one of Examples 176 to 179, wherein the PVOH contains two types of PVOH with different degrees of hydrolysis.

[0202] Example 181. An ophthalmic pharmaceutical product according to any one of Examples 176-180, wherein two types of PVOH differ from each other in their chain length.

[0203] An ophthalmic pharmaceutical product according to any one of Examples 176 to 181, comprising PVOH having a degree of hydrolysis of 97% or more and PVOH having a degree of hydrolysis of 93% or less.

[0204] Example 183. An ophthalmic pharmaceutical product according to any one of Examples 176 to 182, wherein the majority of the PVOH has a degree of hydrolysis of 93% or less.

[0205] Example 184. An ophthalmic pharmaceutical product according to any one of Examples 176 to 183, wherein at least two-thirds of the PVOH has a degree of hydrolysis of 93% or less.

[0206] Example 185. An ophthalmic pharmaceutical product according to any one of Examples 176-184, wherein at least one of the one or more APIs is for the treatment of presbyopia.

[0207] An ophthalmic pharmaceutical product according to any one of Examples 176 to 185, wherein at least one of the one or more APIs is pilocarpine, phentolamine mesylate, oxymetazoline, carbachol, phospholine iodide, brimonidine, aceline and choline lipoate.

[0208] Example 187. An ophthalmic pharmaceutical product according to any one of Examples 176 to 186, wherein the ophthalmic pharmaceutical product is configured to be located between the conjunctiva of the eye and the eyelid that covers the eyeball, and the device has a retaining portion, and is sized and shaped such that when the device is located between the conjunctiva of the eye and the eyelid, the movement of the eyelid relative to the eyeball presses the retaining portion against the eyelid with sufficient force to move the ophthalmic device across the eyeball together with the eyelid.

[0209] Example 188. Ophthalmic pharmaceutical products, The posterior surface is configured to be adjacent to the ocular surface when the ophthalmic pharmaceutical product is inside the eye, The anterior surface defines the height from the ocular surface, A retaining portion defined between a part of the rear surface and a corresponding part of the front surface, wherein two of the heights of the retaining portion, which are spaced a maximum of 1 mm apart from each other, differ from each other by at least 1 mm in height. An ophthalmic pharmaceutical product, including, as described in any one of Examples 176 to 186.

[0210] Example 189. Ophthalmic pharmaceutical products, The posterior surface is configured to be adjacent to the ocular surface when the ophthalmic pharmaceutical product is inside the eye, The anterior surface defines the height from the ocular surface, A retaining portion defined between a portion of the rear surface and a corresponding portion of the front surface, wherein two points on the front surface are spaced at least 1 mm apart from each other along the front surface and each has an inclination of at least 45° with respect to the eye surface. An ophthalmic pharmaceutical product, including, as described in any one of Examples 176-188.

[0211] Example 190. An ophthalmic pharmaceutical product according to any one of Examples 176 to 189, wherein the ophthalmic pharmaceutical product is an ophthalmic device according to at least one of Examples 1, 37, 84, 85, and 136.

[0212] Example 191. A method for treating presbyopia, comprising dissolving a presbyopia treatment drug from any one of the pharmaceutical products described in Examples 174-189 continuously for at least 5 minutes onto the surface of an eye diagnosed with presbyopia.

[0213] Example 192. An ophthalmic device according to any one of Examples 1 to 173, configured to dissolve an ophthalmic lubricant on the ocular surface, wherein the ophthalmic lubricant has a mass content of at least half the mass content of the ophthalmic device.

[0214] Example 193. An ophthalmic device having an arbitrary mass content and configured to dissolve an ophthalmic lubricant on the ocular surface, wherein the ophthalmic lubricant has a mass content of at least half the mass content of the ophthalmic device.

[0215] Example 194. A method for treating a dry eye disease, comprising administering the ophthalmic device described in Example 192 or 193 to a patient in need of treatment.

[0216] Example 195. An ophthalmic device, a. A body containing an elastomer matrix, wherein the elastomer matrix contains 5 wt% to 45 wt% water and at least 50 wt% ophthalmic lubricant, of which 5 wt% to 33 wt% is polyvinyl alcohol (PVOH). The main unit is i. A posterior surface configured to fit the surface of the eye below the eyelid, ii. The front surface that defines the height of the main body from the surface of the eye, iii. A retaining portion defined between a part of the front and a part of the rear, wherein the angle of inclination of the front extending from the rear is greater than 45 degrees, Characterized by the main body, b. A pharmacoactive ingredient (API) for treating ocular conditions, wherein the API is supported by an elastomer matrix and released from the matrix under wet conditions, Ophthalmic devices, including [specific components / features].

[0217] Example 196. The ophthalmic device according to Example 195, wherein the PVOH comprises two or more types of PVOH that differ from each other in either degree of hydrolysis (HD) or chain length.

[0218] Example 197. An ophthalmic device according to Example 195 or Example 196, wherein each of two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix.

[0219] Example 198. Two or more types of PVOH, one of which has a long chain and is completely hydrolyzed, a. Having short chains and being partially hydrolyzed, b. Having long chains and being partially hydrolyzed, c. Having a short chain and being completely hydrolyzed, An ophthalmic device according to any one of Examples 195 to 197, comprising one of at least one of the following.

[0220] Example 199. a. The short chain monomer units are 200 to 2,000. b. The long chain monomer units are 2,200 to 5,000. c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or higher, and d. The degree of hydrolysis of partially hydrolyzed PVOH is 95% or less. An ophthalmic device as described in any one of Examples 195-198.

[0221] Example 200. An ophthalmic device according to any one of Examples 195 to 199, wherein the PVOH comprises two or more types of PVOH having different degrees of hydrolysis (HD).

[0222] An ophthalmic device according to any one of Examples 195-200, wherein the chain length difference of the two types of PVOH is at least 1,000 and they have similar degrees of hydrolysis, with both degrees of hydrolysis being 97%-100%.

[0223] Example 202. An ophthalmic device according to any one of Examples 195 to 201, wherein the first of two or more types has a degree of hydrolysis of 97% to 100%.

[0224] Example 203. An ophthalmic device according to any one of Examples 195 to 202, wherein the second of two or more types has a degree of hydrolysis of less than 93%.

[0225] Example 204. An ophthalmic device according to any one of Examples 195 to 203, wherein the second of two or more types has a degree of hydrolysis of 80% to 93%.

[0226] Example 205. An ophthalmic device according to any one of Examples 195 to 204, wherein the first of two or more types has a chain length of more than 2,500 units.

[0227] Example 206. An ophthalmic device according to any one of Examples 195 to 205, wherein the second of two or more types has a chain length of less than 1,500 units.

[0228] An ophthalmic device according to any one of Examples 195 to 206, wherein the relationship between the first type of PVOH and the second type of PVOH out of two or more types is approximately 3:1 to approximately 1:3.

[0229] An ophthalmic device according to any one of Examples 195 to 207, wherein the first of two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

[0230] Example 209. An ophthalmic device according to any one of Examples 195-208, wherein the second type of PVOH accounts for more than 50% of the PVOH.

[0231] Example 210. An ophthalmic device according to any one of Examples 195-209, wherein at least two types of PVOH determine the degradation rate of the ophthalmic device.

[0232] Example 211. An ophthalmic device according to any one of Examples 195 to 210, wherein the decomposition rate includes the rate at which a predetermined change occurs in a predetermined mechanical property in artificial tear fluid (STF).

[0233] Example 212. An ophthalmic device according to any one of Examples 195 to 211, wherein the total mass content of PVOH and one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding water.

[0234] Example 213. An ophthalmic device according to any one of Examples 195-212, characterized by an elastomer matrix that exhibits substantially isotropic swelling when immersed in simulated tear fluid for 5 minutes at room temperature.

[0235] Example 214. An ophthalmic device according to any one of Examples 195-213, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

[0236] Example 215. An ophthalmic device according to any one of Examples 195-214, wherein water accounts for less than 50 wt% of the total mass content of the matrix.

[0237] Example 216. An ophthalmic device according to any one of Examples 195-215, substantially free from covalent crosslinking.

[0238] Example 217. An ophthalmic device according to any one of Examples 195 to 216, wherein each of the multiple ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

[0239] An ophthalmic device according to any one of Examples 195 to 217, wherein the ophthalmologically acceptable lubricant or viscous agent of Example 218 comprises polyethylene glycol (PEG), and the mass content of PEG in the elastomer matrix is ​​approximately equal to the mass content of PVOH.

[0240] An ophthalmic device according to any one of Examples 195 to 218, wherein at least 35% of the ophthalmologically acceptable lubricant or viscous agent in Example 219 consists of glycerol and propylene glycol.

[0241] Example 220. An ophthalmic device according to any one of Examples 195-219, wherein the elastomer matrix is ​​impregnated with an ophthalmologically acceptable pharmaceutically active ingredient.

[0242] Example 221. An ophthalmic device according to any one of Examples 195 to 220, which can be obtained by mixing the API with water and an ophthalmic lubricant to obtain a mother liquor, and drying the mother liquor at room temperature.

[0243] Example 222. An ophthalmic device according to any one of Examples 195-221, which can obtain the mother liquor without heating.

[0244] Example 223. An ophthalmic device has the following mechanical characteristics: a. Tensile strength of 0.01 MPa to 10 MPa, b. Young's modulus for 0.05 MPa to 10 MPa, and c. Elongation at fracture of 50% to 1,000% An ophthalmic device as described in any one of Examples 195-222, characterized by at least one of the following.

[0245] Example 224. An ophthalmic device according to any one of Examples 195-223, wherein the ophthalmic device is configured to disintegrate within the eye and lose at least 50% of its weight within two hours within the eye.

[0246] Example 225. An ophthalmic device according to any one of Examples 195 to 224, wherein the ophthalmic device is attached and a retaining portion is configured to hold the device in place when the eye rotates.

[0247] Example 226. An ophthalmic device according to any one of Examples 195 to 225, wherein a first height, measured perpendicular to the reference plane from a first point on the posterior surface to a corresponding point on the anterior surface, differs by at least 1 mm from a second height, measured perpendicular to the reference plane from a second point on the posterior surface to a corresponding point on the anterior surface, and the second point is up to 1 mm away from the first point.

[0248] Example 227. An ophthalmic device according to any one of Examples 195-226, having a size and shape such that it is completely covered by the eyelid when placed below the lower eyelid.

[0249] Example 228. An ophthalmic device according to any one of Examples 195-227, wherein the ophthalmic device is configured for self-administration.

[0250] Example 229. The ophthalmic device according to any one of Examples 195 to 228, wherein the device is configured to be attached away from the round lid.

[0251] Example 230. An ophthalmic pharmaceutical product for treating presbyopia, a. An elastomer matrix, i. 5 wt% to 45 wt% water, ii. At least 50 wt% ophthalmic lubricant, including, among which 5 wt% to 33 wt% is polyvinyl alcohol (PVOH), an elastomer matrix, b. A pharmaceutical active ingredient (API) that can be used for treating presbyopia, An ophthalmic pharmaceutical product containing.

[0252] Example 231. The ophthalmic pharmaceutical product according to Example 230, wherein the ophthalmic pharmaceutical product is the ophthalmic device according to any one of Examples 1 to 229.

[0253] Example 232. A method for treating presbyopia, including continuously eluting at least for 5 minutes a pharmaceutical active ingredient that can be used for treating presbyopia from the pharmaceutical product according to any one of Examples 174 to 189 on the conjunctiva of an eye diagnosed with presbyopia.

[0254] Example 233. A method for treating an eye suffering from dry eye syndrome, including topically administering to the eye an ophthalmic device containing an elastomer matrix having a mass content rate of eluting an ophthalmic lubricant on the surface of the eye, and the eluted ophthalmic lubricant accounting for 50% or more of the mass content rate of the matrix.

[0255] Example 234. A method for treating an eye suffering from dry eye syndrome, including topically administering to the eye the ophthalmic device according to any one of Examples 36 to 64 and 160 to 204.

[0256] Example 235. The method according to Example 234, wherein the ophthalmic device does not contain any APIs other than polyvinyl alcohol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

[0257] Example 236. The method according to Example 234 or Example 235, wherein the ophthalmic device is the ophthalmic device described in any one of the preceding claims.

[0258] Example 237. An ophthalmic pharmaceutical product used for the treatment of presbyopia, a. Elastomer matrix, i. 5 wt% to 45 wt% water, ii. At least 50 wt% of an ophthalmic lubricant, An elastomer matrix containing, of which 5 wt% to 33 wt% is polyvinyl alcohol (PVOH), b. Active pharmaceutical ingredients (APIs) that can be used to treat presbyopia, Ophthalmic pharmaceutical products, including [specific ingredient / feature].

[0259] Example 238. The ophthalmic pharmaceutical product according to Example 237, wherein the ophthalmic pharmaceutical product is an ophthalmic device according to any one of the above claims.

[0260] Example 239. A method for treating a dry eye disease, comprising administering an ophthalmic device according to any one of the preceding claims to a patient in need of such treatment.

[0261] Example 240. The method according to Example 238, wherein the ophthalmic device does not contain any APIs other than one or more of the following: polyvinyl alcohol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

[0262] Example 241. An ophthalmic pharmaceutical product used for the treatment of presbyopia, a. Elastomer matrix, i. 5 wt% to 45 wt% water, ii. At least 50 wt% of an ophthalmic lubricant, An elastomer matrix containing, of which 5 wt% to 33 wt% is polyvinyl alcohol (PVOH), b. Active pharmaceutical ingredients (APIs) that can be used to treat presbyopia, Ophthalmic pharmaceutical products, including [specific ingredient / feature].

[0263] Example 242. The ophthalmic pharmaceutical product according to Example 241, wherein the ophthalmic pharmaceutical product is an ophthalmic device according to any one of the preceding claims.

[0264] Example 243. A method for treating a dry eye disease, comprising administering an ophthalmic device according to any one of the preceding claims to a patient in need of such treatment.

[0265] Example 244. The method according to Example 243, wherein the ophthalmic device does not contain any APIs other than one or more of the following: polyvinyl alcohol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

[0266] Example 245. An ophthalmic device configured to be present between the ocular surface of the eye and the eyelid, comprising a body made of an elastomeric matrix containing water, one or more PVOHs, and one or more organic plasticizers, where the body is i. a rear surface adjacent to the ocular surface when the ophthalmic device is worn, ii. a front surface adjacent to the eyelid covering the ocular surface when the ophthalmic device is worn, iii. a holding portion defined between a part of the front surface and a part of the rear surface, characterized by an ophthalmic device in which the ratio of the total mass of one or more organic plasticizers and one or more PVOHs is at least 2:1.

[0267] Example 246. The ophthalmic device according to Example 245, wherein the holding portion is configured to move the ophthalmic device together with the eyelid when the eyelid moves relative to the eyeball.

[0268] Example 247. The ophthalmic device according to Example 245 or Example 246, wherein the angle of inclination of the front surface extending from the rear surface is greater than 45 degrees.

[0269] Example 248. The ophthalmic device according to any one of Examples 245 to 247, wherein the relationship between the width and the length of the ophthalmic device is about 1:1 to about 1:3.

[0270] Example 249. The ophthalmic device according to any one of Examples 245 to 248, wherein the body swells isotropically when immersed in simulated tears for 15 minutes or less.

[0271] Example 250. The ophthalmic device according to any one of Examples 245 to 249, further comprising at least one ophthalmically acceptable pharmaceutical active ingredient (API).

[0272] Example 251. The ophthalmic device according to any one of Examples 245 to 250, wherein water accounts for 5 wt% to 50 wt% of the elastomeric matrix.

[0273] Example 252. An ophthalmic device according to any one of Examples 245 to 251, wherein the ophthalmic device is configured to undergo a weight increase of 50% or less when immersed in simulated tear solution for 15 minutes or less.

[0274] Example 253. An ophthalmic device according to any one of Examples 245-252, wherein the ophthalmic device can be obtained without freezing from a liquid solution containing water, an ophthalmologically acceptable pharmaceutically active ingredient (API), PVOH, and a water-soluble organic liquid.

[0275] Example 254. An ophthalmic device according to any one of Examples 245-253, containing two or more types of PVOH.

[0276] An ophthalmic device according to any one of Examples 245-254, wherein the ratio between two or more types of PVOH is such that the ophthalmic device disintegrates within 24 hours under simulated tear fluid (STF).

[0277] An ophthalmic device according to any one of Examples 245-255, wherein the ratio of two or more types of PVOH is such that the ophthalmic device maintains its original shape in artificial tears (STF) for the first 10 minutes.

[0278] Example 257. An ophthalmic device as described in any one of Examples 245-256, which is visible to the naked eye against the conjunctiva of the eye.

[0279] Example 258. An ophthalmic device according to any one of Examples 245-257, wherein the ophthalmic device is elongated and symmetrical, and all orientations of the device are equivalent as long as the elongated side of the device is in a given direction.

[0280] Example 259. An ophthalmic device according to any one of Examples 245 to 258, wherein the retaining portion is defined by the height between the posterior and anterior surfaces, and a first height, measured from a first point on the posterior surface to a corresponding point on the anterior surface, differs by at least 1 mm from a second height, measured from a second point on the posterior surface to a corresponding point on the anterior surface, and the second point is at most 1 mm away from the first point.

[0281] Example 260. An ophthalmic device according to any one of Examples 245-259, wherein the main body contains multiple ophthalmic lubricants.

[0282] Example 261. An ophthalmic device according to any one of Examples 245 to 260, wherein each of the multiple ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

[0283] Example 262. An ophthalmic device according to any one of Examples 245 to 261, wherein the PVOH comprises two or more types of PVOH that differ from each other in terms of chain length, degree of hydrolysis, or both.

[0284] An ophthalmic device according to any one of Examples 245 to 262, wherein at least 35 wt% of two or more types of PVOH have a degree of hydrolysis of less than 90%.

[0285] Example 264. An ophthalmic device according to any one of Examples 245 to 263, wherein the ophthalmic lubricant contains polyethylene glycol (PEG), and the mass content of PEG in the elastomer matrix is ​​approximately equal to the mass content of PVOH.

[0286] Example 265. An ophthalmic device according to any one of Examples 245 to 264, wherein at least 35% of the ophthalmic lubricant consists of glycerol and propylene glycol.

[0287] Example 266. An ophthalmic device according to any one of Examples 245-265, wherein the elastomer matrix is ​​impregnated with an ophthalmologically acceptable pharmaceutically active ingredient.

[0288] An ophthalmic device according to any one of Examples 245 to 266, which can be obtained by mixing the API with water and an ophthalmic lubricant to obtain a mother liquor, and drying the mother liquor at room temperature.

[0289] Example 268. An ophthalmic device according to any one of Examples 245-267, which can obtain the mother liquor without heating it.

[0290] Example 269. An ophthalmic device described in any one of Examples 245-268, which allows the API to be obtained without heating.

[0291] Example 270. An ophthalmic device has the following mechanical characteristics: a. Tensile strength of 0.05 MPa to 10 MPa, b. Young's modulus for 0.05 MPa to 10 MPa, and c. Elongation at fracture of 50% to 1,000% An ophthalmic device as described in any one of Examples 245-269, characterized by at least one of the above.

[0292] Example 271. An ophthalmic device according to any one of Examples 245-270, wherein the ophthalmic device is configured to lose at least 50% of its weight within two hours in the eye.

[0293] Example 272. An ophthalmic device according to any one of Examples 245 to 271, wherein the retaining portion is configured to hold the ophthalmic device in place when the ophthalmic device is attached and the eye rotates.

[0294] Example 273. An ophthalmic device according to any one of Examples 245 to 272, wherein a first height, measured perpendicular to the reference plane from a first point on the posterior surface to a corresponding point on the anterior surface, differs by at least 1 mm from a second height, measured perpendicular to the reference plane from a second point on the posterior surface to a corresponding point on the anterior surface, and the second point is at most 1 mm away from the first point.

[0295] Example 274. An ophthalmic device according to any one of Examples 245-273, having a size and shape such that it is completely covered by the lower eyelid when placed beneath it.

[0296] Example 275. An ophthalmic device as described in any one of Examples 245-274, wherein the ophthalmic device is configured for self-administration.

[0297] Example 276. An ophthalmic device according to any one of Examples 245-275, wherein the device is configured to be worn away from the fornix of the eye.

[0298] Example 277. An ophthalmic device according to any one of Examples 245 to 276, comprising two or more types of PVOH, each of which accounts for at least 10% of the total amount of PVOH in the matrix.

[0299] Example 278. Contains two or more types of PVOH, where two or more types of PVOH have long chains and are completely hydrolyzed, a. Having short chains and being partially hydrolyzed, b. Having long chains and being partially hydrolyzed, c. Having a short chain and being completely hydrolyzed, An ophthalmic device according to any one of Examples 245 to 277, comprising one of at least one of the following.

[0300] Example 279. a. The short chain monomer units are 200 to 2,000. b. The long chain monomer units are 2,200 to 5,000. c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or higher, and d. The amount of partially hydrolyzed PVOH is 95% or less. An ophthalmic device as described in any one of Examples 245-278.

[0301] An ophthalmic device according to any one of Examples 245 to 279, comprising two or more types of PVOH, wherein two of the PVOH types differ by at least 1,000 units in chain length, and both have similar degrees of hydrolysis of 97% to 100%.

[0302] An ophthalmic device according to any one of Examples 245 to 280, comprising two or more types of PVOH, wherein the first of the two or more types has a degree of hydrolysis of 97% to 100%.

[0303] An ophthalmic device according to any one of Examples 245 to 281, wherein the second of two or more types has a degree of hydrolysis of less than 93%.

[0304] Example 283. An ophthalmic device according to any one of Examples 245 to 282, comprising two or more types of PVOH, wherein the second of the two or more types has a degree of hydrolysis of 80% to 93%.

[0305] Example 284. An ophthalmic device according to any one of Examples 245 to 283, comprising two or more types of PVOH, wherein the first of the two or more types has a chain length of more than 2,500 units.

[0306] Example 285. An ophthalmic device according to any one of Examples 245 to 284, comprising two or more types of PVOH, wherein the second of the two or more types has a chain length of less than 1,500 units.

[0307] Example 286. An ophthalmic device according to any one of Examples 245 to 285, comprising two or more types of PVOH, wherein the ratio between the first type of PVOH and the second type of PVOH is approximately 3:1 to approximately 1:3.

[0308] An ophthalmic device according to any one of Examples 245 to 286, comprising two or more types of PVOH, wherein the first of the two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of the two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

[0309] Example 288. An ophthalmic device according to any one of Examples 245-287, containing two or more types of PVOH, with the second type of PVOH accounting for more than 50% of the PVOH.

[0310] Example 289. An ophthalmic device according to any one of Examples 245 to 288, comprising two or more types of PVOH, wherein at least two types of PVOH determine the degradation rate of the ophthalmic device.

[0311] Example 290. An ophthalmic device according to any one of Examples 245 to 289, wherein the decomposition rate includes the rate at which a predetermined change occurs in a predetermined mechanical property in artificial tear fluid (STF).

[0312] Example 291. An ophthalmic device according to any one of Examples 245 to 290, wherein the total mass content of PVOH and one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding water.

[0313] Example 292. An ophthalmic device according to any one of Examples 245-291, characterized by an elastomer matrix exhibiting substantially isotropic swelling when immersed in simulated tear fluid for 5 minutes at room temperature.

[0314] Example 293. An ophthalmic device according to any one of Examples 245-292, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

[0315] Example 294. An ophthalmic device according to any one of Examples 245-293, wherein water accounts for less than 50 wt% of the total mass content of the matrix.

[0316] Example 295. An ophthalmic device according to any one of Examples 245-294, substantially free from covalent crosslinking.

[0317] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as those generally understood by those skilled in the art in which the invention relates. Similar or equivalent methods and materials may be used in carrying out or testing embodiments of the invention, but exemplary methods and / or materials are described below. In case of any conflict, the patent specification containing the definitions shall prevail. Furthermore, the materials, methods and examples are illustrative and not necessarily intended to be limiting.

[0318] Several embodiments of the present invention are described herein only as examples, with reference to the accompanying drawings. It is emphasized hereby that the details shown are illustrative and for illustrative purposes only, as the drawings are referred to in detail. In this regard, the description made in conjunction with the drawings will make it clear to those skilled in the art how embodiments of the present invention may be carried out. [Brief explanation of the drawing]

[0319] [Figure 1] This figure shows a method of using an ophthalmic device according to several embodiments of the present invention. [Figure 2] This figure shows a treatment method using an ophthalmic device according to several embodiments of the present invention. [Figure 3A] This is a simplified schematic cross-section of an eye. [Figure 3B] This is a simplified schematic cross-sectional view of an ophthalmic device positioned appropriately on the eye surface when the eye is closed, according to several embodiments of the present invention. [Figure 3C] This is a simplified schematic cross-sectional view of an ophthalmic device positioned appropriately on the eye surface when the eye is open, according to several embodiments of the present invention. [Figure 3D] This is a simplified schematic top view of an ophthalmic device positioned on the eye surface according to several embodiments of the present invention. [Figure 4A] This is a simplified schematic top view of an ophthalmic device positioned on the eye surface according to several embodiments of the present invention. [Figure 4B]This is a simplified schematic cross-sectional view of an ophthalmic device positioned appropriately on the eye surface when the eye is closed, according to several embodiments of the present invention. [Figure 5] This describes a method of using an ophthalmic device according to several embodiments of the present invention. [Figure 6A] This is a simplified schematic top view of an ophthalmic device 600 positioned appropriately on the ocular surface below the eyelid, according to several embodiments of the present invention. [Figure 6B] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 7] This is a simplified schematic diagram showing a partial cross-section of a device according to several embodiments of the present invention. [Figure 8] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 9] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 10] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 11] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 12] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 13A] This is a simplified schematic diagram of an ophthalmic device according to several embodiments of the present invention. [Figure 13B] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 13C] This is a simplified schematic top view of an ophthalmic device according to several embodiments of the present invention. [Figure 14] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 15A] This is a simplified schematic top view of an ophthalmic device according to several embodiments of the present invention. [Figure 15B]This is a simplified schematic diagram of an ophthalmic device according to several embodiments of the present invention. [Figure 15C] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 15D] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 16] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 17] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 18] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 19] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 20] This is a simplified schematic top view of a device according to several embodiments of the present invention. [Figure 21] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 22] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 23] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 24] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 25A] This is a simplified schematic cross-sectional view of a device placed on the eye surface according to several embodiments of the present invention. [Figure 25B] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 26] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 27A] This is a simplified schematic top view of an ophthalmic device according to several embodiments of the present invention. [Figure 27B] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 27C] This is a simplified schematic cross-sectional view of device 2700 according to several embodiments of the present invention. [Figure 28] This describes a disassembly process for an ophthalmic device according to several embodiments of the present invention. [Figure 29] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 30] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 31A] This is a simplified schematic cross-sectional view of an ophthalmic device on the eye surface according to several embodiments of the present invention. [Figure 31B] This is a simplified schematic diagram of an ophthalmic device according to several embodiments of the present invention. [Figure 31C] This is a simplified schematic diagram of an ophthalmic device according to several embodiments of the present invention. [Figure 32] This is a simplified schematic cross-sectional view of a portion of an ophthalmic device according to several embodiments of the present invention. [Figure 33] This is a simplified schematic cross-sectional view of a portion of an ophthalmic device according to several embodiments of the present invention. [Figure 34] This is a simplified schematic cross-sectional view of a portion of an ophthalmic device according to several embodiments of the present invention. [Figure 35] This is a simplified schematic cross-sectional view of a portion of an ophthalmic device according to several embodiments of the present invention. [Figure 36] This is a simplified schematic cross-sectional view of a portion of an ophthalmic device according to several embodiments of the present invention. [Figure 37] This is a simplified schematic cross-sectional view of a portion of an ophthalmic device according to several embodiments of the present invention. [Figure 38] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 39]This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 40] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 41] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 42] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 43] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 44] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 45] This is a simplified schematic cross-sectional view of a two-layer device according to several embodiments of the present invention. [Figure 46] This is a simplified schematic cross-sectional view of a two-layer device according to several embodiments of the present invention. [Figure 47] This is a simplified schematic cross-sectional view of a two-layer device according to several embodiments of the present invention. [Figure 48] This is a simplified schematic cross-sectional view of a two-layer device according to several embodiments of the present invention. [Figure 49] This is a simplified schematic cross-sectional view of a two-layer device according to several embodiments of the present invention. [Figure 50] This is a simplified schematic cross-sectional view of a two-layer device according to several embodiments of the present invention. [Figure 51] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 52] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 53] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 54] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 55] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 56] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 57] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 58] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 59A] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 59B] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 60] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 61] This is a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention. [Figure 62A] This is a simplified schematic cross-sectional view of a portion of the ocular surface according to several embodiments of the present invention. [Figure 62B] This is a simplified schematic cross-sectional view of an ophthalmic device on the eye surface according to several embodiments of the present invention. [Figure 62C] This is a simplified schematic cross-sectional view of an ophthalmic device on the eye surface according to several embodiments of the present invention. [Figure 63] This is a simplified schematic cross-sectional view of a part of a device on the eye surface according to several embodiments of the present invention. [Figure 64] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 65] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 66] This is a simplified schematic cross-sectional view of a multilayer device according to several embodiments of the present invention. [Figure 67]This is a simplified schematic cross-sectional view of a portion of the device as its residence time elapses, according to several embodiments of the present invention. [Figure 68] This is a flowchart of the device's decay progression according to several embodiments of the present invention. [Figure 69] This is a simplified schematic cross-sectional view of a device as its residence time elapses, according to several embodiments of the present invention. [Figure 70] This is a simplified schematic cross-sectional view of a device as its residence time elapses, according to several embodiments of the present invention. [Figure 71] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 72] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 73] This is a simplified schematic cross-sectional view of a device on the ocular surface 7304 according to several embodiments of the present invention. [Figure 74] This is a simplified schematic cross-sectional view of a film according to several embodiments of the present invention. [Figure 75] This is a manufacturing method according to several embodiments of the present invention. [Figure 76] This is a simplified schematic cross-sectional view of a device according to several embodiments of the present invention. [Figure 77] This graph shows exemplary degradation characteristics of three different elastomer matrix compositions, as they change over time under wet conditions, according to several embodiments of the present invention. [Figure 78] This graph shows the decomposition of several matrices during wet and dry cycles according to several embodiments of the present invention. [Figure 79] This graph plots the clinical results obtained according to embodiments of the present invention in comparison with publicly available data related to eye drops. [Figure 80] This graph shows the effect of an ophthalmic device according to an embodiment of the present invention on the near visual acuity (NVA) of two patients. [Modes for carrying out the invention]

[0320] The present invention relates, in some embodiments thereof, to shaped polyvinyl alcohol (PVOH)-based elastomer matrices for ophthalmic applications, and more specifically, to such matrices that are biodegradable or bioerodible. In this specification, the terms “biodegradable” and “bioerodible” (as well as their variations such as biodegradability and bioerodibility) are used without distinction. For example, a matrix may be considered biodegradable if it is mechanically eroded within the body.

[0321] overview The present invention provides, in some embodiments thereof, ophthalmic pharmaceutical products, their use, and methods for manufacturing the same. The ophthalmic pharmaceutical product is preferably an ophthalmic device. All features of the pharmaceutical products described herein may also be found in any ophthalmic device described herein, and vice versa. In some embodiments, the ophthalmic device is configured to remain between the bulbar conjunctiva (ocular conjunctiva) and the eyelid, more specifically, between the ocular conjunctiva covering the sclera and the palpebral conjunctiva (tarsal conjunctiva) covering the eyelid. The tarsal conjunctiva and the ocular conjunctiva meet at the conjunctival fornix, and in some embodiments, the device is configured to be attached away from the fornix and closer to the eyelid opening. In some embodiments, the ophthalmic device extends below either the lower or upper eyelid. A potential advantage of having a device positioned under only one, rather than both, is the potential to provide a smaller, more comfortable device that, in some embodiments, can be inserted by the patient themselves and optionally removed. In some embodiments, the ophthalmic device is located between the eyeball and the eyelid and is configured to move with the eyelid when the eyelid moves relative to the eyeball. In some embodiments, the ophthalmic device is located between the eyeball and the eyelid and is configured to remain on the eyelid side when the eyeball moves relative to the eyelid. In some embodiments, the ophthalmic device is configured to be located between the ocular surface and the eyelid and comprises a body made of an elastomer matrix, the elastomer matrix comprising water, one or more types of PVOH and one or more organic plasticizers. In some embodiments, the body is characterized by a posterior surface adjacent to the ocular surface when the ophthalmic device is attached, a front surface adjacent to the eyelid covering the ocular surface when the ophthalmic device is attached, and a retaining portion defined between a portion of the front surface and a portion of the posterior surface, wherein the retaining portion has a rim structured to move the ophthalmic device with the eyelid when the eyelid moves relative to the eyeball.

[0322] In some embodiments, the ophthalmic device is configured to remain between the conjunctiva and the tarsal conjunctiva even when the eyelid or eyeball moves relative to each other. In some embodiments, the device moves across the eyeball with the eyelid while moving between the eyelid and the eyeball, and in other embodiments, the device moves with the eyeball.

[0323] Embodiments in which the device moves with the eyeball or with the eyelid have different balances between gripping force and adhesive force. The gripping force acts between the edge of the eyelid and the edge of the device adjacent to the eyelid, while the adhesive force acts on the rear surface of the device (facing the ocular surface). The adhesive force may include, for example, adhesive friction force (traction force) and / or suction force.

[0324] In some embodiments, the gripping force is greater than the adhesive force, and the ophthalmic device moves across the eyeball along with the eyelid. In some embodiments, the adhesive force is greater than the gripping force, and the ophthalmic device moves (or stays) with the eyeball.

[0325] In some embodiments, the ophthalmic device is configured to have increased gripping force by including a retaining portion having a steep anterior edge. In some embodiments, the anterior edge is the edge adjacent to the eyelid opening. In some embodiments, the retaining portion is part of the ophthalmic device and is defined between a portion of the posterior surface and a corresponding portion of the anterior surface, which is the surface of the device facing the eyelid. In some embodiments, the anterior surface defines the height from the ocular surface. In some embodiments, in order to have increased gripping force, the retaining portion is optionally structured such that two of the heights defined by the corresponding portions of the anterior surface are close to each other and have a large height difference between them, forming an angle of 45 degrees or more between the anterior surface and the ocular surface. For example, the two heights may be separated by a distance of up to 1 mm from each other, but have a height difference of at least 1 mm from each other.

[0326] In some embodiments, the ophthalmic device is configured to have increased adhesion by including, for example, one or more cavities configured to receive a portion of the conjunctiva in order to increase friction between the device and the eyeball. Similarly, in some embodiments, the ophthalmic device is configured to have increased gripping force by including, for example, one or more cavities configured to receive a portion of the tarsal conjunctiva in order to increase friction between the device and the eyelid.

[0327] In some embodiments, the ophthalmic device may be configured to move across the eyeball together with the eyelid by having no cavity on the posterior surface and a steep retaining portion.

[0328] In some embodiments, the ophthalmic device may be configured to move with the eyeball by having a non-steep retaining portion and a cavity on its rear surface.

[0329] In some embodiments, the ophthalmic device has both a posterior surface with one or more cavities and a steep retaining portion, and the behavior of the device as the eyeball moves relative to the eyelid is determined by the relative effect of the cavities and the steepness of the retaining portion.

[0330] In some embodiments having a steep retaining portion, the retaining portion is optionally pressed firmly against the eyelid with sufficient force to overcome friction between the posterior surface and the ocular surface. Such strong pressure between the eyelid and the retaining portion can cause significant discomfort to the wearer of the device. In some embodiments, to prevent such discomfort, the retaining portion is made of a material that is soft enough not to irritate the eye even when pressed against the eyelid with the strong force required to pull the device together with the eyelid.

[0331] In some embodiments, the required flexibility can be achieved by using an elastomer matrix compounded with water, PVOH, and a large amount of plasticizer. The amount of plasticizer may be considered large when it is greater than or preferably at least twice the mass of PVOH. In some such embodiments, the combined mass of PVOH and plasticizer is 70% or more of the total mass of the matrix excluding water. In some embodiments, the PVOH comprises two or more types of PVOH that differ from each other in either or both degree of hydrolysis (HD) and / or chain length. In some embodiments, each of the two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix. In some embodiments, the two or more types of PVOH include one type having a long chain and being completely hydrolyzed, and one type having a short chain and being partially hydrolyzed, a long chain and being partially hydrolyzed, and a short chain and being completely hydrolyzed, with at least one of these. In some embodiments, the short chain consists of 200 to 2,000 monomer units, the long chain consists of 2,200 to 5,000 monomer units, the fully hydrolyzed PVOH has a degree of hydrolysis of 97% or more, and the partially hydrolyzed PVOH has a degree of hydrolysis of 95% or less.

[0332] In some embodiments, the required flexibility can be achieved by using an elastomer matrix having at least one of the following mechanical properties. Tensile strength of 0.01 MPa to 10 MPa, with an optional range of 0.05 MPa to 10 MPa. Optionally, the tensile strength may be less than 10 MPa, less than 4 MPa, less than 3 MPa, or less than 2 MPa. The modulus of elasticity is 0.01 MPa to 2.5 MPa, with an optional range of 0.05 MPa to 10 MPa. Optionally, the modulus of elasticity may be less than 10 MPa, less than 4 MPa, less than 3 MPa, or less than 2 MPa. Elongation at break of 50% to 1,000% or more. See also the mechanical properties shown in Example 8 below.

[0333] In some embodiments, after an ophthalmic device remains in the eye for a certain period of time (e.g., 5 or 10 minutes, 30 minutes, 1 hour, or 4 hours, or an intermediate duration), the properties of the elastomer matrix change. In some embodiments, this process, commonly referred to herein as “degradation,” can alter the balance of forces between the device and the tarsal conjunctiva, on the one hand, and between the device and the conjunctiva, on the other hand. In some embodiments, degradation improves the device’s fit to its anatomical location. For example, the device may loosen its adhesion to the ocular surface (conjunctiva) by, for example, a change in shape, or strengthen its adhesion to the eyelid surface (tarsal conjunctiva) by, for example, the development of mucosal adhesion properties of the matrix or a better fit to the conjunctiva. Thus, in some embodiments, after remaining in the eye for a certain period of time, degradation of the device may have the effect of detaching the device from the ocular surface while adhering it to the eyelid, preventing the device from reaching the cornea (e.g., floating on the tear film) and being rapidly expelled from the cornea by the natural evacuation mechanism.

[0334] In some embodiments, the ophthalmic device is configured to remain in contact with the outer surface of the eyeball and / or the inner surface of the eyelid for an extended period, for example, up to 24 hours, without activating mechanisms that naturally expel foreign objects from the eye, such as increased eye movement, blinking, and eye rubbing. In some embodiments, such mechanisms may be activated for a short period immediately after administration of the ophthalmic device, but this is quickly reduced to the extent that the eye is not irritated and the ophthalmic device remains in the eye without being expelled.

[0335] In some embodiments, this rapid ocular soothing is achieved, among other things, by the matrix being soft and pliable, especially in its dry form, even before it is inserted into the eye. In some embodiments, the pliability of the matrix may be expressed as being easily adaptable to new environments and being able to bend and / or fold without wrinkles, cracks, or breakage. In some embodiments, softness, combined with flexibility (or pliability), allows the matrix to bend and conform its shape to the anatomical space into which it is inserted, for example, the space available in the lid wiper space between the lower eyelid and the conjunctiva of the eye. In some embodiments, bending and shape conformation improve the fit between the ophthalmic device and the intraocular space over time, thus potentially reducing discomfort and allowing for longer-term retention of the ophthalmic device on the eye.

[0336] In some embodiments, ophthalmic devices are configured to be stored for extended periods under dry conditions without losing their shape, flexibility, and / or elasticity, and thus enjoy a particularly long shelf life.

[0337] In some embodiments, the ophthalmic device is configured to shrink and swell when removed from dry conditions and exposed to water (or wet conditions).

[0338] In some embodiments, the contraction and swelling are characterized by being substantially isotropic. As used herein, substantially isotropic contraction or swelling means that each dimension undergoes a size change of the same amount ± about 20%. For example, in an ophthalmic device having a rectangular shape, the length, width, and thickness (which can be measured, for example, by calipers) change by the same amount ± about 20%. In an ophthalmic device having a cylindrical shape, the diameter and height change by the same amount ± about 20%. In some embodiments, in addition to being isotropic, the total swelling is 50% by volume or less, i.e., each dimension (e.g., length, width, and depth) may increase by about 15% or less in the first minute or two after immersion in water. In some embodiments, after the first minute or two, the pharmaceutical product may not continue to swell but may become smaller, for example, by decomposition. In some embodiments, the requirement of isotropic swelling of 50% or less means that the increase along each direction (e.g., as measured by calipers) is 18%(15±3)% or less. In some embodiments, the ophthalmic device and / or the elastomer matrix contained therein is characterized by exhibiting substantially isotropic swelling when immersed in simulated tear solution at room temperature for 5, 10, or 15 minutes. In some embodiments, the ophthalmic device or elastomer matrix exhibits swelling of less than 50% by volume when immersed in simulated tear solution at room temperature for 5, 10, or 15 minutes.

[0339] In some embodiments, isotropic swelling and contraction causes the ophthalmic device to have substantially the same shape (if not the same volume) under dry and wet conditions (at least for the first few minutes under wet conditions). As used herein, dry conditions are conditions in which the pharmaceutical product is kept at ambient humidity but without direct contact with liquids, including water and aqueous liquids. Wet conditions are conditions in which the pharmaceutical product is kept in contact with aqueous liquids, such as water, tears, or simulated tears.

[0340] In some embodiments, the ability to remain in the eye with only limited and brief stimulation may also benefit from the shape of the ophthalmic device. For example, in some embodiments, a soft and flexible matrix is ​​shaped to include a retaining portion adapted to hold the pharmaceutical product in place, for example, in the space between the conjunctiva and the eyelid. In some embodiments, the retaining portion is adapted to hold the pharmaceutical product in the space between the conjunctiva and the eyelid as the device is worn and the eye rotates. In some embodiments, the retaining portion can prevent the ophthalmic device from slipping out of the other part of the eye, for example, under the upper eyelid, which could cause more discomfort despite the high level of softness and flexibility of the device. In some embodiments, the softness, flexibility, and pliability of the pharmaceutical product allow it to move relatively large (e.g., 15 mm parallel to the ocular surface) without obstructing the eye. 2 ~35mm 2 It makes it possible to have an area and a maximum thickness of 5 mm.

[0341] In some embodiments, the mechanical properties related to the flexibility and elasticity of an ophthalmic device typically include at least one of the following: (i) tensile strength of 0.01 MPa to 2 MPa, optionally 0.05 MPa to 1 MPa; (ii) modulus of elasticity (also known as Young's modulus under tension) of 0.01 MPa to 2.5 MPa, optionally 0.05 MPa to 2 MPa; (iii) elongation at break of about 50% to about 1,000%, optionally about 100% to about 900%, optionally 200% to 600%; and (iv) compressive modulus of elasticity (also known as Young's modulus under compression) of 0.05 MPa to 2.5 MPa, optionally 0.1 MPa to 2.0 MPa.

[0342] One aspect of several embodiments of the present invention relates to an elastomer matrix (hereinafter simply referred to as "matrix" or "matrices / matrixes") comprising one or more PVOHs to achieve a matrix having determined and / or desired mechanical properties. In some embodiments, the elastomer matrix is ​​PVOH-based in the sense that PVOH is the sole or primary film-forming polymer in the matrix.

[0343] In some embodiments, the matrix is ​​designed to dissolve and / or decompose under wet conditions according to predetermined timeline requirements. In some embodiments, the decomposition timeline is controlled by selecting the composition of one or more types of PVOH in the matrix. In some embodiments, the composition is optionally characterized by the various types of PVOH contained in the composition and their relative masses, or by the mass portion of the total PVOH provided by each type.

[0344] In some embodiments, when “wetting conditions” is referred to, it should be understood to relate to conditions in which the matrix of the present invention is in direct contact with a liquid (immersed in a liquid, or after immersion in a liquid, and before the liquid evaporates or is wiped away). In some embodiments, the liquid is a naturally occurring bodily fluid (including, but not limited to, blood, saliva, tears, excrement, body tissue, and interstitial fluid), an aqueous solution (e.g., an aqueous solution of one or more organic plasticizers), a buffer solution, and any combination thereof. In some embodiments, the liquid is naturally occurring or simulates a naturally occurring fluid such as artificial tears. In some embodiments, the artificial tears are based on an aqueous solution containing about 0.67% sodium chloride, about 0.2% sodium bicarbonate, and about 0.008% calcium chloride. In some embodiments, “wetting conditions” refers to the conditions under which the matrix is ​​placed on human mucosal tissue, e.g., cheek tissue or the ocular surface.

[0345] In some embodiments, the term matrix degradation is defined as a change in the properties of the matrix over time under wet conditions, and “degradability” is defined as the tendency or rate of degradation.

[0346] In some embodiments, changes in properties may include, for example, a change or loss of the mass of one or more of the matrix components or the entire matrix. For example, a plasticizer detaching from the ophthalmic device may be replaced by water, but in some embodiments, PVOH itself may detach from the ophthalmic device, and therefore the device may lose weight. Alternatively or additionally, changes may include changes in the mechanical properties, shape, and / or size of the matrix. Alternatively or additionally, decomposition may be expressed as dissolution, breakage, tearing, and / or collapse of the matrix. Generally, decomposition may result from the breaking of bonds between different components of the matrix (e.g., PVOH, plasticizer, and water), while each component remains intact. In some embodiments, decomposition allows for the removal of the ophthalmic device, or the elastomer matrix contained in the device, from the eye by tears that can wash away the components, fragments, and / or remnants of the matrix from the eye.

[0347] In some embodiments, the type of decomposition, such as a change from a soft solid to slime, dissolution, mass loss, or change in tearability, may depend on the type of PVOH contained in the matrix. For example, we have found that some matrices containing long-chain complete hydrolysis (LCFH) PVOH and short-chain partial hydrolysis (SCPH) PVOH tend to become “slimy” when immersed in simulated tears (STF). In such embodiments, increased sliminess may be accompanied by a decrease in compressive modulus over time under STF. In some embodiments, some matrices containing LCFH PVOH and long-chain partial hydrolysis (LCPH) PVOH tend to become more readily soluble in STF, meaning they can dissolve in a clear solution in cold water. In some embodiments, some matrices containing LCFH PVOH and short-chain complete hydrolysis (SCFH) PVOH tend to tear more easily the longer they are immersed in STF. In some embodiments, increased susceptibility of such a matrix to tearing may be accompanied by a decrease in compressive strength over time under STF conditions.

[0348] See also the exemplary mechanical properties in Example 8 below.

[0349] In some embodiments, degradation may eliminate the need to remove the matrix from the body. For example, the degradation products may be naturally excreted from the body, for example, by tears (if the matrix is ​​used in the eye) or by urine (if the matrix is ​​used in the bladder). In the case of ophthalmic devices, ophthalmic devices made from a degradable matrix may remain in the eye for a certain period of time and then naturally detach from the eye without the need for active removal. For example, the device may completely dissolve and detach from the eye with tears, or it may break down into small pieces so that it can be excreted from the eye as any other foreign body.

[0350] In some embodiments, slight pressure on a detachable matrix (e.g., used as an ophthalmic device) can immediately alter the morphology or integrity of the matrix, allowing the ophthalmic device to be spontaneously ejected immediately after being pressed.

[0351] In some embodiments, disintegration allows the matrix to remain in the anatomical site of use by acquiring a comfortable shape and / or viscosity. For example, an ophthalmic device may acquire a shape that fits into the space between the conjunctiva and the tarsal conjunctiva, where it can remain without causing discomfort to the patient until it disintegrates and is expelled from the eye. In some embodiments, on its way out of the eye, the disintegrated device may encounter the cornea, causing temporary discomfort.

[0352] In some embodiments, the terms “dissolve” and “degrade” are interchangeable and refer to a process in which the elastomer matrix changes, for example, a process under wet conditions. The change may be, for example, a change from a solid state to a completely degraded state. The change may be, for example, a loss of mass. In some embodiments, a completely degraded state may be defined as, for example, a degraded state of the matrix when the matrix is ​​so broken down into particles of such small size that it is not visible to the naked eye, and / or, in a matrix used or applied to any tissue such as the eyelid, for example, when the matrix elastically changes shape and / or does not maintain a defined shape under certain external pressures, such as pressure on the matrix from the eyelid. The terms “shape” and “geometry” are interchangeable and refer to the form of the matrix.

[0353] In some embodiments, the matrix comprises a mixture of two or more types of PVOH. In some embodiments, the difference between the types of PVOH lies in one or more of the degree of hydrolysis and the length of the PVOH chain. In some embodiments, the greater the amount of highly hydrolyzed PVOH in the matrix, the longer the time it takes for the matrix to decompose completely. In some embodiments, the PVOH comprises two or more types of PVOH that differ from each other in one or both of the degree of hydrolysis (HD) and / or chain length. In some embodiments, each of the two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix. In some embodiments, the two or more types of PVOH include one type that has a long chain and is completely hydrolyzed, and one type that has a short chain and is partially hydrolyzed, has a long chain and is partially hydrolyzed, and has a short chain and is completely hydrolyzed, at least one of these. In some embodiments, the short chain consists of 200 to 2,000 monomer units, the long chain consists of 2,200 to 5,000 monomer units, the fully hydrolyzed PVOH has a degree of hydrolysis of 97% or more, and the partially hydrolyzed PVOH has a degree of hydrolysis of 95% or less.

[0354] In some embodiments, the number of PVOH types is three or more.

[0355] In some embodiments, two of the PVOH types differ in chain length by, for example, at least 1,000 or 1,500 units. In some such embodiments, two of the PVOH types have similar degrees of hydrolysis, for example, 97% to 100%.

[0356] In some embodiments, two of the PVOH types have different degrees of hydrolysis, for example, one having 97% or more DH and the other 93%, 90%, or less. In some such embodiments, the two PVOH types also have different chain lengths, for example, by at least 1,000 or 1,500 units. For example, the PVOH type with a higher degree of hydrolysis may have a longer chain. In another example, the PVOH type with a higher degree of hydrolysis may have a shorter chain. In some embodiments, when two of the PVOH types differ in their degrees of hydrolysis, the two PVOH types have similar lengths and differ from each other by, for example, less than 500 units.

[0357] In some embodiments, short-chain PVOH has an average chain length of about 200 to about 2,000 monomer units, and long-chain PVOH has an average chain length of about 2,200 to about 5,000 monomer units. In some embodiments, fully hydrolyzed PVOH has a degree of hydrolysis of 97% or more, and partially hydrolyzed PVOH has a degree of hydrolysis of 94% or less. In some embodiments, the short chain has a molecular weight of about 50 kg / mol to less than about 80 kg / mol, while the long chain has a molecular weight of about 50 kg / mol to greater than about 80 kg / mol.

[0358] In some embodiments, the matrix is ​​specifically designed to maintain its geometric shape / form under wet conditions before the decomposition process begins. The decomposition process may begin after 1 minute under wet conditions in some embodiments, and after several hours or within an intermediate time under wet conditions in other embodiments. Matrix that maintains its geometric shape can be shaped outside the body (e.g., the eye) and is known to retain the same shape for at least any period after contact with the body.

[0359] In some embodiments, the elastomer matrix comprises PVOH, one or more organic plasticizers, and optionally water. In some embodiments, the elastomer matrix is ​​characterized in that the ratio of the total mass of one or more plasticizers to the total mass of various types of PVOH is at least 2:1.

[0360] In other words, the total mass of plasticizer / the total mass of PVOH ≥ 2 / 1.

[0361] This ratio is referred to in this specification as the "combined mass ratio."

[0362] In some embodiments, the elastomer matrix contains two or more plasticizers.

[0363] In some embodiments, the matrix is ​​characterized by maintaining its geometric shape when in contact with a moist environment, for example, when in contact with the eye or other body tissue. In some embodiments, in addition to maintaining its geometric shape when in contact with a moist environment, the matrix optionally increases in volume. In some embodiments, the volume increase is 50% or less. In some embodiments, the volume changes but the geometric shape is maintained because the swelling is the same in all directions. In some embodiments, the elastomer matrix is ​​characterized by exhibiting substantially isotropic swelling when immersed in simulated tear solution at room temperature for 5, 10, or 15 minutes. In some embodiments, the elastomer matrix exhibits swelling of less than 50% by volume when immersed in simulated tear solution at room temperature for 5, 10, or 15 minutes.

[0364] In some embodiments, the mechanical properties and / or degradability of the elastomer matrix depend on the types of PVOH used to form the matrix and their respective masses. For example, if the PVOH consists of mostly long-chain complete hydrolysis (LCFH) PVOH and a small amount of short-chain partial hydrolysis (SCPH) PVOH, the matrix degrades more slowly than when LCFH PVOH is a small amount of PVOH in the matrix and SCPH PVOH is the majority.

[0365] The following table (Table 1) provides examples of several commercially available types of PVOH. The list is taken from the Mowiol® brand, but similar materials are available from other sources. The type of PVOH labeled "30k" in the following table (Table 1) is not a Mowiol brand product. All types of PVOH used in the examples and measurements described herein were performed using PVOH sold under the Emprove® brand or 30k PVOH (Sigma Aldrich 8.21039).

[0366] [Table 1]

[0367] In some embodiments, the elastomer matrix is ​​used as an ophthalmic device or constitutes part of an ophthalmic device. In some embodiments, the ophthalmic device may be configured to be placed on the surface of the eye, preferably on the sclera. In some embodiments, options for placing the ophthalmic device include one or more of the following methods: local (sclera, cornea), subconjunctival, conjunctiva, choroidal, intravitreous, anterior chamber, subretinal, or on or inside the eye or other body part. Examples include intramuscular injection into body cavities (bladder, stomach), joints, etc. In some embodiments, a potential advantage of placing on the sclera is that the sclera is potentially less sensitive (to pain, irritation, etc.) than the cornea, and therefore designing the matrix to contact only the sclera potentially results in a matrix that is more favorable to the user. In some embodiments, depending on the type and composition of PVOH contained in the elastomer matrix, complete decomposition occurs, for example, between 0.5 and 12 hours after contact with the eye. Optionally, between 0.5 and 24 hours. Optionally, the timeframe is between 0.5 hours and 48 hours. Optionally, it is longer than 48 hours. In some embodiments, a potential advantage of controlling the decompression time is that it allows the user to use the ophthalmic device at a convenient and / or selected time interval (e.g., while the user is sleeping, or to allow the device to operate within a desired time frame).

[0368] In some embodiments, the elastomer matrix is ​​characterized by a tensile strength of 10 MPa, 4 MPa, or less than 3 MPa, preferably less than 2 MPa, under dry conditions. Additionally or alternatively, the elastomer matrix is ​​characterized by an elasticity (also known as Young's modulus) of 0.01 MPa to 10 MPa, 4 MPa, or 3 MPa, preferably 0.01 MPa to 2 MPa, under dry conditions. Additionally or alternatively, the elastomer matrix is ​​characterized by an elongation at break of at least 50%, for example, 50% to 900% or 50% to 1,000%, under dry conditions. In some embodiments, a potential advantage of having a matrix characterized by the above mechanical properties is that it potentially reduces user discomfort and thereby potentially improves compliance.

[0369] A broad range of several embodiments relates to an ophthalmic device made of an elastomer matrix disclosed herein for the treatment and / or protection of the eye, which, once placed on the eye, remains inside the eye, for example, between the eyelid and the ocular surface. In some embodiments, the device remains on the eye for at least 15 minutes. In some embodiments, the device remains inside the eye. For example, the device does not move from the area of ​​the eye on which it is placed and / or is not ejected from the eye during the treatment period. Herein, in some embodiments, the device is placed under the eyelid and / or on a portion of the eyeball. On the other hand, in some embodiments, the device remains comfortable for the user to wear.

[0370] Preferably, the device does not cover even a portion of the cornea. Not touching the cornea can have the effect of reducing irritation (compared to devices that touch the cornea), because the cornea is very sensitive to foreign objects. In some embodiments, the device is configured to be placed on the conjunctiva of the eye, which is relatively insensitive to irritation. A device configured to be attached to the conjunctiva of the eye may also be effective because it is relatively easy to attach and remove compared to devices attached to other parts of the eye.

[0371] In some embodiments, the device remains on and / or in place (e.g., under the eyelid) during the user / patient's normal activities, such as blinking, tearing, crying, sweating, washing (e.g., showering), walking, exercising, and sleeping. In some embodiments, the device remains on and / or in place for patients while the eye is mostly closed, such as during sleep and / or in a semi-conscious or unconscious state. In some embodiments, the ophthalmic device contains one or more pharmaceutically active ingredients (APIs) and / or other compounds that are released (e.g., eluted from the device) while the device remains in the eye.

[0372] One aspect of several embodiments relates to an ophthalmic device fabricated from an elastomer matrix disclosed herein, which is configured to remain in a position below the eyelid of the eye. In some embodiments, optionally, a portion of the ophthalmic device remains in a position below the eyelid of the eye, while another portion of the ophthalmic device optionally extends outside the eyelid without reaching the cornea. In some embodiments, the ophthalmic device is configured to be entirely present and present between the surface of the eye and the eyelid. In some embodiments, the ophthalmic device does not include any portion extending outside the eyelid. In some embodiments, the device is configured to be present on the conjunctiva of the eyeball and below the eyelid, optionally even during opening and closing of the eye (e.g., blinking).

[0373] In some embodiments, the ophthalmic device includes a retaining portion having a size and / or shape that keeps the device under the eyelid. In some embodiments, the retaining portion is the entire ophthalmic device. In some embodiments, the device has additional portions to the retaining portion. In some embodiments, the device may include two or more retaining portions. Herein, in some embodiments, the retaining portion is sufficiently thick and / or sufficiently high and / or steeply sloped relative to the ocular tissue so that the device remains in position under the eyelid. For example, the front surface of the device is sufficiently high and / or sloped relative to the ocular tissue, e.g., the edge of the eyelid and / or the tarsal plate.

[0374] In some embodiments, the thickness and / or height extends sufficiently in one or more directions. In some embodiments, the retaining portion includes a front surface that exhibits sufficient inclination with respect to the ocular tissue. In some embodiments, the properties of the retaining portion depend on one or more of the following: the shape of the front surface of the retaining portion, the thickness of the device (e.g., defined between the front and rear surfaces), and the shape of the rear surface. In some embodiments, when on the ocular surface, the properties of the retaining portion further depend on the material properties of the device (e.g., flexibility), such as those disclosed with respect to the exemplary elastomer matrix disclosed herein, and the forces the device experiences when it is on the ocular surface and / or below the eyelid. In some embodiments, when the front surface of the retaining portion is flat, the height of the retaining portion is the same as the thickness of the device in the retaining portion. In some embodiments, the height and / or inclination of the retaining portion with respect to the front surface in a dry configuration and / or hydrated configuration is defined, for example, for a device in a relaxed configuration, and with respect to the plane on which the device rests, and / or on the plane connecting most of the circumference of the edge of the device. In some embodiments, the height and / or inclination of the retaining portion when in a dry configuration and / or hydrated configuration is defined, for example, for a device in a relaxed configuration on a surface having a radius of curvature of approximately 12 mm in both directions, for example, the expected radius of curvature of the eyeball on which the device is placed (e.g., a sphere having a radius of curvature in one or more directions), for example, the radius of curvature of the adult human sclera. In some embodiments, the height and / or inclination of the retaining portion when in a dry configuration and / or hydrated configuration is defined, for example, for a device when on the ocular surface, where, in some embodiments, the device is deformed (e.g., flattened) by suction between the device and the ocular surface and / or pressure on the device (e.g., by the eyelid).

[0375] In some embodiments, the height of a portion(s) of the device is affected by the curvature of the rear surface, where, for devices of the same thickness, a higher curvature results in a greater height. In some embodiments, the retaining portion has a portion having a sufficiently steep incline, followed by a portion having sufficient thickness and / or length and / or area to allow the device to be held under the eyelid. Here, for example, the retaining portion has a height having a distance from the front edge (or edge of the retaining portion) as described herein, and may also include a portion having a height exceeding the retaining height, where the portion has a sufficient range to allow the device to be held under the eyelid. For example, the portion having the retaining height has a height of at least 1 mm 2 , or 0.5mm 2 ~3mm 2 , or 0.5mm 2 ~2mm 2 It may have an area of ​​0.5 mm to 5 mm, or 1 mm to 3 mm. In some embodiments, the maximum height of the device is less than 3 times, or less than 2 times, or less than 1.5 times the holding height. In some embodiments, the device holding portion has a height of at least 1 mm at a position 1 mm inward from the edge of the device (e.g., the front edge) and / or the edge of the holding portion. In some embodiments, the device holding portion has a height of 50 micrometers to 2,500 micrometers or 500 micrometers to 1,000 micrometers at a position 0.5 mm, 1 mm, or 2 mm from the front edge of the device.

[0376] In some embodiments, the ophthalmic device includes a body having a posterior and an anterior surface. In some embodiments, the posterior and anterior surfaces are distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (for example, one is convex and the other concave, one is curved and the other is flat, etc.).

[0377] The retaining portion can be defined between the corresponding posterior and anterior portions. When the device is properly placed in the eye, the posterior portion is adjacent to the surface of the eye, and the anterior portion is adjacent to the eyelid, defining the height from the ocular surface.

[0378] Before being placed in the eye, the device may be positioned in a relaxed configuration on a flat reference plane such that its posterior surface faces the flat reference plane. In such a position, the anterior surface defines a height from the flat reference plane. In some embodiments, the reference plane is defined as the (actual or virtual) surface facing the posterior surface of the device in the relaxed configuration.

[0379] In some embodiments, two heights measured from the ocular surface and spaced a maximum of 1 mm apart from each other differ only in that the height difference is at least 1 mm. Alternatively or additionally, two heights measured from a flat reference plane and spaced a maximum of 1 mm apart from each other differ only in that the height difference is at least 1 mm. In some embodiments, the reference plane is defined as the (actual or virtual) surface facing the rear surface of the device in the relaxation configuration.

[0380] In some embodiments, a first height measured from a first point on the rear surface to a corresponding point on the front surface differs by at least 1 mm from a second height measured from a second point on the rear surface to a corresponding point on the front surface, where the second point is located at a distance of up to 1 mm from the first point.

[0381] In some embodiments, the ophthalmic device includes a body that includes a posterior surface adjacent to the ocular surface when the ophthalmic device is fitted, and an anterior surface adjacent to the eyelid when the ophthalmic device is fitted. The retaining portion may be defined by the height between the posterior and anterior surfaces. In some embodiments, at least some of the heights between the posterior and anterior surfaces differ from each other by at least 1 mm when measured from two points on the posterior surface that are spaced a maximum of 1 mm apart from each other.

[0382] In some embodiments, a device retaining portion is formed, at least partially, when the device enters the eye. For example, in some embodiments, the device is crumpled and / or flattened and / or folded to provide a retaining portion. In some embodiments, this is due to the movement of the eyelid. In some embodiments, the retaining portion of the ophthalmic device allows the ophthalmic device to remain between the eyelid and the ocular surface. In some embodiments, when the ophthalmic device is positioned below the lower eyelid, the retaining portion prevents the ophthalmic device from coming out of the lower eyelid. In some embodiments, when the ophthalmic device is positioned below the upper eyelid, the retaining portion prevents the ophthalmic device from coming out of the upper eyelid.

[0383] In some embodiments, the retaining portion is configured to prevent the ophthalmic device from sliding under the upper eyelid when the ophthalmic device is positioned on the surface of the eye (whether accidentally or not) but not under either the lower or upper eyelid (e.g., positioned in a visible location on the surface of the eye). Optionally, such a retaining portion allows the ophthalmic device to slide under the lower eyelid when the user closes their eyes. Thus, in some embodiments, a device positioned in the visible part of the eye can find its way to the conjunctiva and remain there thanks to the retaining portion.

[0384] In some embodiments, the device is thick, for example, with a maximum and / or average thickness of 400 to 2,500 microns, or at least about 1 mm, between the front and rear surfaces. A potential advantage of such thickness (optionally combined with the extent of the retaining portion and / or the device) is the corresponding volume of the device, which in some embodiments allows for the loading of therapeutic material into the device. In some embodiments, the device has a volume of 1 to 500 microliters, or 1 to 100 microliters, or 1 to 50 microliters, or 10 to 50 microliters, or 20 to 100 microliters. Additionally, another potential advantage is that such thickness of the device does not interfere with the user and potentially improves compliance with the use of the device, particularly in devices fabricated with a soft elastomer matrix as described herein. In some embodiments, the device has a mass of 1 mg to 500 mg, or 1 mg to 100 mg, or 1 mg to 50 mg, or 10 mg to 50 mg, or 10 mg to 30 mg, or 15 mg to 20 mg, or 20 mg to 100 mg. In some embodiments, the ophthalmic device contains 1 mg to 500 mg, or 20 mg to 500 mg, or 20 mg to 150 mg, or 20 mg to 120 mg of active pharmaceutical ingredients (APIs) (or more). In some embodiments, the ophthalmic device is formed from 1% to 50%, or 1% to 20%, of active pharmaceutical ingredients (APIs) (or more). In some embodiments, the whole or majority of the ophthalmic device is active pharmaceutical ingredients (APIs) (or more), for example, the device is at least 80%, or at least 90%, or at least 95%, or at least 99% by weight and / or volume of active pharmaceutical ingredients (APIs).In some embodiments, the ophthalmic device contains a large amount of active pharmaceutical ingredients (APIs) (which may be multiple) (e.g., about 1 mg to about 20 mg, or more than 1 mg, or more than 20 mg, or 0.2 mg to 1 mg, or 1 mg to 4 mg, or 4 mg to 10 mg, or 10 mg to 20 mg, or 20 mg to 50 mg) and / or can dissolve such ingredients (which may be multiple) onto the surface of the eye.

[0385] The potential advantage of ophthalmic devices is their ability to deliver active pharmaceutical ingredients (APIs) (in amounts greater than those administered by topical formulations, or sometimes multiple formulations) to the surface of the eye and / or inside the eyeball (potentially as an alternative to intraocular injection). For example, in the case of a topical formulation with up to 1% concentration of an active pharmaceutical ingredient (API) applied as eye drops, for example, 30 microliters is 0.3 mg, and a significant portion of the API is expected to be naturally washed out of the eye within minutes. The potential advantage of ophthalmic devices that elute large amounts of drug while remaining on the ocular surface is their ability to provide and / or maintain appropriate concentrations of the drug in the intranasal region and / or the brain and / or head and / or other target organs, and / or provide systemic drug delivery (e.g., for the administration of cannabinoids and / or opioids, e.g., for "microdosing").

[0386] In some embodiments, the device is used for recreational drug use.

[0387] In some embodiments, the retaining portion of the device is part of the device, adjacent to the anterior edge of the device, and in some embodiments, includes the anterior edge of the device. Here, in some embodiments, the anterior edge of the device is defined as part of the circumferential edge of the device closest to the edge of the eyelid and / or the opening when the device is below the eyelid. Although not bound by theory, in some embodiments, it is theorized that the interaction between the tarsal plate of the eyelid and the inclination of the device (and / or the retaining portion of the device) acts to retain the device in the eyelid behind the tarsal plate. In some embodiments, the interaction between the tarsal plate and the device is related to the deformation of the eyelid tissue around the device. In some embodiments, alternatively or additionally to the force of the tarsal plate, a reaction force of tissue due to the deformation of the eyelid acts on the device to prevent movement of the device, e.g., out of the eyelid and / or deeper into the fornix of the eye. Alternatively or additionally, in some embodiments, a force acts between the eyeball and the rear surface of the device to prevent movement of the device, where, in some embodiments, the force includes eyelid pressure on the device, then a reaction force to the eyelid pressure on the eyeball, and / or an attractive force between the device and the eyeball. In some embodiments, the retaining portion extends around the ophthalmic device, for example, 20% to 100% of the periphery of the ophthalmic device. A potential advantage of a device having a retaining portion extending around a large portion of the device (e.g., more than 50%) is the increased retaining force on the device (e.g., of the tarsal plate) and / or the increased likelihood that the edge of the eyelid will continue to interact with the retaining portion in the event of device rotation.

[0388] In some embodiments, the ophthalmic device is symmetrical, for example, having rotational symmetry around one or more axes. For example, the ophthalmic device may be symmetrical around an axis perpendicular to the ocular surface on which the device is placed. Additionally or alternatively, the ophthalmic device may be symmetrical around a central axis, for example, an axis defined as the axis connecting the centers of the anterior and posterior surfaces. In some embodiments, as described above, the posterior and anterior surfaces are distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other flat, etc.). A potential advantage of rotational symmetry is that it maintains the interaction of the retaining portion with the eyelid margin and / or tarsal plate when the ophthalmic device rotates within the eye while worn.

[0389] In some embodiments, the ophthalmic device includes two or more retaining parts. A potential advantage of multiple retaining parts may be an increased area of ​​retaining part / eyelid interaction for holding the device in place. A potential advantage of such increased area is that if the first retaining part fails and the device slips from under the eyelid and / or the first retaining part slips from under the tarsal plate, the ophthalmic device may be held at least partially under the eyelid by the second retaining part. A potential advantage of having two or more raised parts of the device (e.g., as provided by the retaining parts) is that the raised surfaces facilitate pinch removal. Pinch removal, in some embodiments, is the application of two opposing forces to different parts of the device to break the suction between the device and the ocular surface and / or to push a part(s) of the device (e.g., between the parts to which force is applied) away from the ocular surface. Here, in some embodiments, the opposing forces are applied manually by the user, for example, by the thumb and other fingers, for example, the index finger.

[0390] In some embodiments, an ophthalmic device including multiple retaining parts includes one or more cavities on the rear surface of the device, for example, a cavity for each retaining part.

[0391] In some embodiments, for example, when the device is symmetrical, the retaining portion is formed by the entire edge of the device, or a large portion of the peripheral edge of the device, for example, at least 50%, at least 80%, or at least 90%. A potential advantage of being all or a large portion of the edge of the device is that it increases the likelihood that the device will be held under the eyelid in rotational situations of the device.

[0392] In some embodiments, the ophthalmic device is configured to adhere to the ocular surface on which it is placed. In some embodiments, if the device partially or completely slips away from under the eyelid, the adhesive force of the device to the ocular surface (e.g., the sclera) is sufficient to keep the device on the eye, for example, for at least a short period, e.g., during blinking (in some embodiments, several times, e.g., 1 to 10 blinks). Here, in some embodiments, if the device slips away from under the eyelid and / or appears, the device is returned to under the eyelid (e.g., manually). In some embodiments, the adhesion of the ophthalmic device to the ocular surface is sufficient to prevent rotation of the device. For example, this is the case for devices that are not rotationally symmetric, and / or devices with localized retaining portions, and / or devices with retaining portions asymmetrically positioned on the device. In some embodiments, the adhesion of the ophthalmic device to the ocular surface (e.g., the sclera) is related to the attractive force between the device and the ocular surface. For example, in some embodiments, the posterior surface of the ophthalmic device adjacent to the ocular surface is curved, e.g., concave in one or more directions. This curvature potentially increases the attractive force between the device and the ocular surface. In some embodiments, the curvature of the posterior surface is 0.1 to 1 of the curvature of the sclera in one or more directions. In some embodiments, the radius of curvature of the posterior surface is 1 mm to 15 mm or 1 mm to 10 mm in one or more directions, and / or the ratio to the radius of curvature of the sclera is 0.1 to 2 or 0.5 to 1.

[0393] In some embodiments, a lower curvature of the posterior surface is associated with a reduction in attractive force between the ocular surface and the posterior surface, potentially allowing for repositioning and / or improving user comfort. In some embodiments, the radius of curvature of the posterior surface is lower than the radius of curvature of the sclera in one or more directions, for example, the ratio of the radius of curvature of the posterior surface to the radius of curvature of the sclera is greater than 0.8, e.g., 0.8 to 1. Although a description has been given with respect to the ocular surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood as distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other flat, etc.).

[0394] In some embodiments, different portions of the posterior surface have different radii of curvature, although in some embodiments, each of these has a curvature lower than that of the sclera. In some embodiments, the dimensions and / or ratios (e.g., curvature) described herein are related to the curvature of an average adult human eye, where, for example, in some embodiments, the radius of curvature RS of the sclera is approximately 12 mm. In some embodiments, the dimensions and / or curvature are selected for different anatomical structures, e.g., a child's eye, e.g., an animal's eye, e.g., different surfaces (e.g., a mucosal surface). Here, for example, if the device is used in an eye with different dimensions and / or curvature (e.g., an animal's eye, a child's eye), the size (and may be multiple) and / or curvature (and may be multiple) of the device are scaled for the type of eye and / or for use in a particular eye (e.g., a personally tailored device). Here, for example, one or more dimensions of the device, e.g., the length and / or width of the device footprint, and / or the height and / or slope of the holding area (e.g., as described herein), are scaled using, for example, one or more measurement parameters of the eye in question, e.g., the radius and / or diameter and / or maximum range of the eye.

[0395] In some embodiments, for example, if the surface includes cavities (which may be more) and / or protrusions (which may be more) and / or has a surface texture, the radius of curvature of the surface (and / or edges and / or corners) is defined as the radius of a circle that matches at least 60%, 80%, or 90% of the curvature of the surface (and / or edges and / or corners).

[0396] In some embodiments, the ophthalmic device comprises multiple layers and / or portions having different material properties. In some embodiments, the device comprises one or more of a lubricating layer, a mucosal adhesion layer, and additional layers. In some embodiments, one or more layers comprise a therapeutic material. In some embodiments, the body of the ophthalmic device has a concave rear surface. In some embodiments, the concavity of the rear surface in contact with the ocular surface (e.g., the sclera) increases the adhesion of the device to the ocular surface. The concavity provides, for example, an attractive force between the device and the ocular surface, causing the device to adhere to the ocular surface.

[0397] Optionally, in some embodiments, the radius of curvature of one or more portions of the rear surface of the device is smaller than the radius of curvature of the portion of the eye to which the device is bonded, e.g., the sclera. In some embodiments, the body of the ophthalmic device is not hollow. In some embodiments, the body of the ophthalmic device is made from a continuous material, i.e., it does not contain macroscopic gaps and / or empty areas inside. In some embodiments, gaps or empty areas are defined as macroscopic if they are greater than 0.2 mm. In some embodiments, the body of the ophthalmic device has an elliptical or circular shape. In some embodiments, the body of the ophthalmic device is symmetrical with respect to both its longitudinal axis and its transverse axis. For example, when the ophthalmic device is viewed from the front, the device is symmetrical with respect to its longitudinal axis and its transverse axis.

[0398] In some embodiments, the device has an elliptical and / or oval cross-sectional shape. For example, the rear surface may be elliptical and / or oval.

[0399] In some embodiments, the posterior surface is smooth, potentially reducing irritation associated with contact between the ocular surface and the device, for example. In some embodiments, the posterior surface includes rough areas (which may be more) and / or anchors (which may be more) that potentially increase frictional adhesion between the posterior surface and the ocular surface. In some embodiments, the periphery region of the posterior surface (e.g., and optionally, not the central region which is smooth in some embodiments) is rough and / or includes anchors (which may be more) and / or protrusions and / or cavities. In some embodiments, the posterior surface is smoother than the anterior surface. In some embodiments, both the posterior and anterior surfaces are similarly smooth. In some embodiments, the device includes one or more features to increase adhesion between the device and the sclera. Examples of features include roughness and / or anchors (e.g., cavities (which may be more), protrusions (which may be more), and / or hooks (which may be more)) located on the posterior surface and / or the periphery of the device.

[0400] One aspect of several embodiments relates to an ophthalmic device fabricated from an elastomer matrix disclosed herein, which is configured to remain under the eyelid (e.g., having a retaining portion) but has mobility between the device and the surface of the eyeball and / or allows for fluid flow. Potential advantages of mobility or fluid flow between the device and the eyeball are improved user comfort and / or reduced risk of bacterial growth under the device (e.g., related to tear exchange). In some embodiments, mobility of the device on the surface of the eye relates to a low suction and / or easily breakable suction seal between the posterior surface of the device and the surface of the eyeball. For example, in some embodiments, the posterior surface includes one or more portions that have low concavity (e.g., having the radius of curvature described above), or are not concavity, or are convex, potentially reducing the device's ability to seal with the surface of the eyeball. In some embodiments, the device can form a seal with the surface of the eyeball, for example, having a convex posterior surface and / or a flexible edge, where the seal is easily breakable to allow the device to move (e.g., periodically) on the surface of the eyeball. For example, in some embodiments, the device includes a sealing edge (e.g., flexibility) on only a portion of the device. For example, in some embodiments, the device is elongated, potentially facilitating the breakdown of the attractive force between the device and the ocular surface. Although a description has been given with respect to the ocular surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other flat, etc.).

[0401] One aspect of several embodiments of the present invention relates to an ophthalmic device fabricated from an elastomer matrix disclosed herein, which maintains its size and / or shape both during storage and in use, wherein in some embodiments the device is supplied in a dry form and optionally hydrates during its residence on the ocular surface. Potential advantages include reduced distortion of the device during hydration and / or in use, and / or maintenance of the device's shape and / or mechanical properties in use. For example, the device can be stored in a dry form in which the active pharmaceutical ingredient (API)(or potentially more) is less likely to decompose and / or decomposes more slowly, while potentially extending the device's shelf life. In some embodiments, as the device hydrates (e.g., on the ocular surface), the device increases in volume by less than 20%, less than 15%, less than 10%, or less than 5%. In some embodiments, as the device hydrates, one or more maximum cross-sectional dimensions increase by less than 20%, less than 15%, less than 10%, or less than 5%.

[0402] One aspect of several embodiments of the present invention relates to an ophthalmic device made of an elastomer matrix disclosed herein, which is flexible when dry and when hydrated. Here, in some embodiments, the device is provided in a dry form and optionally hydrates during retention on the ocular surface. A potential advantage of a device that is flexible in a dry form is that it allows the device to be applied to the eye without prior hydration and / or softening. A potential advantage of a flexible ophthalmic device is reduced irritation to the eye, for example, reduced tearing associated with the presence of a device that may wash away therapeutic materials and / or nutrients.

[0403] In some embodiments, as further disclosed below with respect to the elastomer matrix of an ophthalmic device, at least a portion of the ophthalmic device degrades and / or disintegrates in the eye. In some embodiments, the degradation is due to mass loss. In some embodiments, the ophthalmic device is a biocompatible device designed to be partially or completely biodegradable and / or bioerosive. The term biodegradable should be understood as degradation progressing in the body, for example, through changes in mechanical properties, mass loss, and / or changes in shape. Chemical degradation of polymers in the matrix is ​​not required to achieve degradation. Optionally, the PVOH itself maintains its original length, and the bonds (e.g., hydrogen bonds) between the PVOH, plasticizer, and water are broken. In some embodiments, the degradation allows the ophthalmic device, or the elastomer matrix contained in the device, to be removed from the eye, for example, by tears, which can wash away matrix components, fragments, and / or remnants from the eye. For example, in some embodiments, a portion of the device degrades, for example, when the device is adhered to the ocular surface. The one or more parts to be decomposed may include, for example, one or more mucosal adhesive parts and / or one or more lubricating parts. For example, in some embodiments, one or more parts of the device are selected to decompose in the eye in about 1 to 30 minutes, or 15 minutes to 1 hour, or about 0.5 to 8 hours, or 4 to 24 hours, or 12 hours to 3 days, or 1 to 7 days, or 3 days to 2 weeks, or 1 week to 1 month.

[0404] In some embodiments, one or more parts of an ophthalmic device decompose to allow the elution of a therapeutic material. For example, in some embodiments, as the part containing the therapeutic material decomposes, the ophthalmic device elutes the therapeutic material into the eye tissue and / or ophthalmic fluid. For example, in some embodiments, a part decomposes to expose the part containing the therapeutic material. Here, in some embodiments, the decomposed part first covers at least a portion of the part containing the therapeutic material. In some embodiments, when exposed to a biological environment, e.g., a biological system, e.g., the eye, and / or a similar in vitro environment simulating the conditions of a biological system, at least a part of the device decomposes and / or its properties deteriorate.

[0405] In some embodiments, the disintegration and / or degradation of the device is indicated by a change (e.g., a decrease) in one or more of the physical properties of the device, such as the device's integrity, tensile strength, modulus of elasticity, elongation at break, etc.

[0406] In some embodiments, disintegration occurs from the rear to the front, and for example, the device maintains the shape of the front for any period while the device is disintegrating. In some embodiments, disintegration from the rear is faster than disintegration from the front. In some embodiments, the device includes different parts that disintegrate at different speeds. In some embodiments, parts that disintegrate at a slower speed and / or do not disintegrate act to maintain their shape (e.g., the shape of the retaining part) for any period. In some embodiments, the device is designed to break in small pieces, for example, when manual pressure is applied. Here, in some embodiments, the size and / or shape and / or brittleness of the device are selected to provide this feature. Although a description has been given with respect to the ocular surface, in some embodiments, as described above, the rear and front surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the rear and front surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other flat, etc.).

[0407] One aspect of several embodiments of the present invention relates to an ophthalmic device fabricated from an elastomer matrix disclosed herein, having one or more retaining portions and including a thin and / or conforming rim portion. In some embodiments, for example, if the device includes a thin rim portion and / or a portion extending from the body of the device, the retaining portion is defined as a region of the device that satisfies height and / or inclination requirements, e.g., those described above. In some embodiments, the device (e.g., the curvature of one or more portions of the device to generate sufficient suction force to hold the device in place) conforms to the eye. Here, for example, in some embodiments, the rim portion is thin and / or flexible enough to conform to the surface of the eye. In some embodiments, the device has a thin rim, and / or the rim of the device is embedded in the surface of the eye. In some embodiments, moving from the leading edge of the device, the device includes a thin rim followed by a retaining portion. In some embodiments, the step formed between the rim of the device and the surface of the eye, e.g., the step by an adjacent thin rim to the retaining portion, is 1 to 100 microns, or 10 to 50 microns. In some embodiments, the edge characteristics (e.g., shape and / or thickness) described herein relate to all or part of the edge region of the device. For example, a portion of the circumferential edge of the device. For example, 20% to 99%, or 80% to 90%, of the circumference of the device. In some embodiments, different portions of the circumferential edge of the device have different characteristics, such as shape and / or thickness.

[0408] In some embodiments, adhesion to the sclera relates to the adhesion of the device's edges to the sclera and is influenced, for example, by the degree of the device's fit to the sclera and / or the sclera's fit to the device. In some embodiments, the flexibility and / or elasticity of the device improves the seal between the device's edges and the ocular surface. In some embodiments, the device includes one or more edges that are flexible and / or elastic, for example, a portion that is flexible but sufficiently thin. In some embodiments, the device has edges designed for user comfort and / or to increase adhesion to the eyeball.

[0409] In some embodiments, the ophthalmic device has a thin rim. In some embodiments, the rim of the device (e.g., the circumferential rim) has an average thickness of about 15 microns, or about 20 microns, or about 30 microns, or about 50 microns. In some embodiments, the ophthalmic device has a thin rim of about 15 microns or about 20 microns. In some embodiments, the ophthalmic device has a rim thickness of about 5 to 200 microns, or 5 to 200 microns. In some embodiments, for example, instead of having a thin rim, or in some embodiments, if the device has a thin rim circumference only in a portion of its circumference, in some embodiments, the rim of the device is blunt and / or curved and / or rounded, for example, to improve wear comfort for the user. In some embodiments, the rim of the device is sharp, for example, chisel-shaped and / or knife-edge. In some embodiments, the rim of the ophthalmic device is defined as a 0.1 mm to 1 mm rim region of the device, or a 0.1 mm to 0.5 mm rim region. In some embodiments, the edge thickness is measured at 0.1 mm or 0.5 mm from the circumference of the device. In some embodiments, a device with a thin edge provides an improved seal between the edge of the device and the ocular surface. A potential benefit of the seal between the device edge and the ocular surface is an increased attractive force between the device and the ocular surface.

[0410] A potential benefit of a seal between the device edge and the ocular surface is the reduction of debris (e.g., one or more proteins, mucus, oils, and skin cells) between the device and the ocular surface, potentially minimizing the risk of infection associated with the use of ophthalmic devices.

[0411] In some embodiments, the thin-edge device conforms to the shape of the ocular surface at the device edge. In some embodiments, the device edge provides for fixing the device to the ocular surface, e.g., the soft tissue of the conjunctiva, e.g., a soft, thick scleral conjunctiva, clearly about 25 to 40 microns thick, and clearly even thicker in the fornix. In some embodiments, the device is embedded in the ocular surface at the device edge and / or creates a depression in the ocular surface, e.g., the embedding is related to one or more of the pressure between the device edges and / or the softness of the ocular surface. In some embodiments, the portion(s) of the eye deform in the depth direction (e.g., by the device), e.g., at the device edge (and / or in the region(s) adjacent to the device protrusion and / or cavity), e.g., 50 to 500 microns.

[0412] In some embodiments, localized tissue, e.g., tissue areas up to 0.5 mm or 1 mm in size, deforms at the edges of the device. In some embodiments, the edges (and / or edge regions) of the device conform to the shape of the ocular surface. For example, in some embodiments, the edge regions are flexible and / or elastic and / or sufficiently thin to conform to the ocular surface. In some embodiments, the device body is at least partially flexible and / or elastic to conform to the ocular surface, e.g., sufficiently flexible and / or elastic. Potentially, a device body and / or edges that conform to the ocular surface improve user comfort and / or reduce the risk of device detachment.

[0413] In some embodiments, the rear surface includes, for example, one or more cavities or protrusions on the rear surface of the device. While not bound by theory, in some embodiments, it is assumed that the cavities increase the attractive force between the device and the ocular surface, for example, the local attractive force in the cavity. In some embodiments, ocular tissue enters the cavity (for example, under the attractive force of the cavity), potentially increasing adhesion between the device and the eye. A potential benefit of cavities (may be more than one) on the rear surface is an extension of the device's residence time on the eye.

[0414] In some embodiments, the device has multiple cavities, where, in some embodiments, two or more of the cavities are substantially the same in size and / or shape. Hereinafter, in some embodiments, two or more of the cavities differ from each other, for example, in size and / or shape. In some embodiments, the opening size of the cavities is 0.005 mm to 20 mm, or 0.005 mm to 2 mm, or 0.005 mm to 1 mm, or 0.005 mm to 0.5 mm, or 1 mm to 2 mm, 1 mm to 4 mm, or 2 mm to 6 mm, 3 mm to 8 mm, or 4 mm to 10 mm, or 5 mm to 20 mm. In some embodiments, the cavity has a large opening, for example, extending over at least half of the surface area (e.g., the rear surface) and / or having a range of 1 mm to 10 mm, or 1 mm to 8 mm, or 1 mm to 5 mm, or 5 mm to 20 mm. In some embodiments, the cavity opening is of macroscopic or microscopic size. In some embodiments, the cavity depth is 5 microns to 2 mm, or 5 microns to 1 mm, or 5 microns to 400 microns, or 5 microns to 200 microns, 200 microns to 600 microns, 400 microns to 800 microns, 600 microns to 1,500 microns, or 800 microns to 2,000 microns. In an exemplary embodiment, the cavity depth is 400 microns to 1,200 microns. In some embodiments, the cavity extends over a portion of the device thickness, for example, over 10% to 20%, 20% to 30%, 30% to 50%, 50% to 90%, or 80% to 99%, or 90% to 99%, 50% to 70%, or 60% to 90% of the device thickness in the cavity region.

[0415] In some embodiments, the ophthalmic device includes one or more protrusions from one or both sides of the device. In some embodiments, the protrusions (which may be more) have a rounded and / or blunt shape. In some embodiments, the device has multiple protrusions, where, in some embodiments, two or more of the protrusions are substantially the same in size and / or shape. Where, in some embodiments, two or more of the protrusions differ from each other, for example, in size and / or shape. In some embodiments, the size of the protrusions on the surface of the device (e.g., the rear and / or front) is in the range or size of 5 to 400 microns, or 20 to 200 microns, or 200 to 800 microns, or 400 to 1,200 microns, or 600 to 1,500 microns, lower, higher, or intermediate. In some embodiments, the footprint range of the protrusions on the surface of the device is 5 microns to 3 mm, or 5 microns to 1 mm, or 5 microns to 700 microns, or 5 microns to 400 microns, or 3 mm to 6 mm, or 4 mm to 8 mm, or 4 mm to 10 mm, or 6 mm to 12 mm.

[0416] A potential benefit of projections (or multiple projections) is increased adhesion of the ophthalmic device to the ocular surface. In some embodiments, projections (or multiple projections) increase friction between the ocular surfaces. In some embodiments, projections (or multiple projections) increase attraction between the device and the ocular surface (e.g., between the projections). In some embodiments, the ophthalmic device includes, for example, a mucosal adhesive material on the posterior surface of the device, which potentially increases adhesion between the device and the ocular surface on which the device is placed.

[0417] Optionally, in some embodiments, the rear surface includes one or more mucosal adhesive portions. Here, in some embodiments, the mucosal adhesive material(s) increases the adhesion of the device to the ocular surface. In some embodiments, the rear surface includes a mucosal adhesive layer. Here, in some embodiments, the layer covers the rear surface. Alternatively, in some embodiments, the mucosal adhesive layer is a discontinuous surface, where, for example, holes(s) allow, for example, the penetration of water and / or drug transport to the layer beneath the mucosal adhesive layer. In some embodiments, the mucosal adhesive layer has a ring shape with an opening in the center, allowing, for example, the penetration of water and / or drug transport. In some embodiments, the mucosal adhesive layer in the device is provided in a dry and / or semi-hydrated state. Here, in some embodiments, when the device is applied to the eyeball, the mucosal adhesive layer hydrates and becomes adhesive in, for example, less than 10 seconds, less than 30 seconds, or less than 1 minute. In some embodiments, the material / compound / polymer in the mucosal adhesive layer has an adhesive strength of 80% to 200%, or 100% to 200%, or greater than 100%. Here, for example, pectin is defined as having an adhesive strength of 100%. In some embodiments, the mucosal adhesive portion comprises at least one mucosal adhesive compound, which in some embodiments is selected from the group consisting of gelatin, alginate, chitosan, amylose, collagen, sodium polyacrylate, modified starch, elastin, polyacrylic acid, and combinations thereof. In some embodiments, the device exhibits a low-friction surface against the eyelid (e.g., smooth). A potential benefit is a reduction in the likelihood of the device falling off. In some embodiments, the device exhibits a low-friction surface against the ocular surface (e.g., smooth). A potential benefit is a reduction in the likelihood of user discomfort. In some embodiments, the device exhibits the same low level of friction against the eyelid and the ocular surface.

[0418] Optionally, in some embodiments, one or more portions of the front surface of the device are smooth and / or include a lubricating material. Here, the front surface of the device is a surface that is in contact with the inner surface of the eyelid for at least some time. Potentially, in some embodiments, the smooth and / or lubricating material reduces friction between the eyelid and the surface. Potentially, in some embodiments, the smooth and / or lubricating material minimizes irritation to the eye, e.g., the eyelid, e.g., irritation associated with the ophthalmic device.

[0419] In some embodiments, the rear surface is smoother than the front surface. In some embodiments, both the rear and front surfaces are smooth. In some embodiments, a lubricating material layer covers the front surface, where, in some embodiments, the layer is continuous. In some embodiments, the lubricating layer is a discontinuous surface (e.g., including one or more holes) to allow, for example, water penetration and / or drug transport. For example, in some embodiments, the lubricating material layer includes holes. In some embodiments, the front surface accommodates one or more portions of lubricating material, where, in some embodiments, one or more of these portions are connected to other portions (may be more than one) and / or one or more of these portions are not connected to other portions. Optionally, in some embodiments, the lubricating surface is transient, where, in some embodiments, one or more portions of the lubricating material decompose and / or disappear (e.g., absorbed and / or discharged by the eye) before, for example, other portions (may be more than one) of the device decompose. In some embodiments, the material layer has a variable thickness and / or variable material properties (e.g., a lubricating layer and / or a mucosal adhesion layer). Here, for example, upon application to the eye, the material has a larger area on the anterior surface compared to after the residence period on the eye, where, in some embodiments, more rapidly degrading portions (may be more) of the layer (e.g., thinner portions and / or portions having a more rapidly degrading composition) dissolve before other portions (may be more) and expose, for example, a lower layer containing a pharmaceutically active ingredient (API) (may be more) in some embodiments. Although a description has been given with respect to the ocular surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other flat, etc.).

[0420] One aspect of several embodiments of the present invention relates to a kit comprising an ophthalmic device (e.g., one made of an elastomer matrix as described and disclosed herein) and instructions for its use. In some embodiments, the kit includes means for delivering the device into a patient's eye, e.g., an applicator. In some embodiments, the ophthalmic device is packaged together with the applicator. Optionally, in some embodiments, the kit includes a decomposition formulation that, upon contact with the device while it is on the surface of the patient's eye, structurally disintegrates the device and / or accelerates the disintegration of the device. In some embodiments, the device is provided in a multi-device pack, where, in some embodiments, two or more devices are interconnected or separated from each other.

[0421] In some embodiments, the ophthalmic device has one or more of the following properties: flexibility, elasticity, and pliability, for example, to conform to the shape of the eyeball. In some embodiments, the elasticity and / or pliability of the ophthalmic device is similar to that of a soft contact lens. In some embodiments, the ophthalmic device has elasticity or pliability with a Young's modulus of 0.01 MPa to 1.5 MPa, or 0.05 MPa to 0.15 MPa to 1.5 MPa, or 0.25 MPa to 0.35 MPa in one or more directions. In some embodiments, as described above, the required pliability can be achieved by using an elastomer matrix compounded with water, PVOH, and a large amount of plasticizer. The amount of plasticizer may be considered large when it is greater than or preferably at least twice (by mass) the mass of PVOH. In some such embodiments, the combined mass of PVOH and plasticizer is 70% or more of the total mass of the matrix excluding water. In some embodiments, the ophthalmic device has elasticity with a Young's modulus of 0.01 MPa to 2.00 MPa in one or more directions. In some embodiments, the ophthalmic device has elasticity in one or more directions (e.g., Young's modulus of 0.01 MPa to 200 MPa, or 0.05 MPa to 0.15 MPa, or 0.15 MPa to 0.35 MPa) in a dry state. In some embodiments, the ophthalmic device has elasticity in one or more directions (e.g., Young's modulus of 0.01 MPa to 200 MPa, or 0.05 MPa to 0.15 MPa, or 0.01 MPa to 0.35 MPa) in a wet state within the eye. In some embodiments, the ophthalmic device has elasticity that allows for elongation of 10% to 800% or more (in both dry and / or wet states). In some embodiments, the ophthalmic device is rigid, shaped, and, for example, shaped to conform to the shape of the eyeball. In some embodiments, the elasticity and / or hardness of the ophthalmic device is similar to that of a hard or rigid contact lens in one or more directions. In some embodiments, the ophthalmic device has elasticity with a Young's modulus of 0.1 MPa to 200 MPa in one or more directions.In some embodiments, the ophthalmic device has this elasticity in one or more directions in a dry state. In some embodiments, the ophthalmic device has this elasticity in a wet state, for example, within the eye. In some embodiments, the ophthalmic device has layers having different material properties, e.g., elastic and / or flexible (see below for exemplary elastomer matrices of ophthalmic devices). In some embodiments, the ophthalmic device has regions having different material properties, e.g., elastic and / or flexible. In some embodiments, the device is flexible, potentially allowing the device to conform to the shape of the eye surface, potentially improving user comfort (e.g., allowing the eyelids to move smoothly over the device with little or no interference and / or discomfort), and / or reducing the detachment force on the device. In some embodiments, the flexible device has a concave rear surface, where an attractive force between the device and the ocular surface (e.g., related to the interaction between the concavity of the rear surface and the ocular surface) flattens the device on the ocular surface. In some embodiments, the elasticity of the device increases the attractive force between the device and the ocular surface, causing the device to adhere to the eye. Here, for example, in some embodiments, elasticity compensates for the low concave curvature of the rear surface of the device. Although a description has been given with respect to the ocular surface, in some embodiments, as described above, the rear and front surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the rear and front surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other is flat, etc.).

[0422] In some embodiments, the flexibility and / or elasticity of the device improves the seal between the device edge and the ocular surface. In some embodiments, one or more portions are configured to fit the ocular surface and / or a portion of the ocular surface and / or an opening. In some embodiments, the device is selected to fit the size of the inferior or superior conjunctival sac, where the device deforms the sac only slightly, for example, by a maximum of 2 mm, for example, by an amount that is comfortable for the user and / or does not harm the ocular surface and / or eyelid and / or other tissues (may be more). For example, in some embodiments, only the retaining portion deforms the sac. It has been found that a device with a height of 2 mm can be comfortable, and in some embodiments, devices with a height of 4 mm to 6 mm can be comfortable. In some embodiments, a device width of 5 mm to 10 mm has been found to be comfortable. In some embodiments, the ophthalmic device has a thickness of less than 3 mm, or less than 2.5 mm, or less than 2 mm, or less than 1.5 mm, or less than 1 mm, or less than 0.8 mm, or less than 0.6 mm, or less than 0.5 mm, or less than 0.4 mm, or less than 0.3 mm. In some embodiments, the ophthalmic device has a thickness of more than 3 mm, or more than 2.5 mm, or more than 2 mm, or more than 1.5 mm, or more than 1 mm, or more than 0.8 mm, or more than 0.6 mm, or more than 0.5 mm, or more than 0.4 mm, or more than 0.3 mm.

[0423] In some embodiments, the pressure between the eye and the device is increased by increasing the thickness of the device and / or the thickness of the edge region of the device. Here, in some embodiments, the increased pressure (and / or the seal between the eye and the device, e.g., related to pressure and / or contouring of the eye to the device or the device to the eye) reduces tear film penetration between the device and the ocular surface.

[0424] In some embodiments, the device is small, for example, small enough to fit (e.g., completely) within the space under the eyelid. In some embodiments, the maximum and / or average range of the device is about 4mm to 12mm, or 4mm to 10mm, or 4mm to 8mm, or 3mm to 8mm, 1mm to 8mm, or 4mm to 6mm. In some embodiments, the ophthalmic device has a size of about 4mm (e.g., maximum and / or average range). In other embodiments, the device has dimensions of about 0.5mm to about 20mm in maximum size. Potential advantages of small-sized devices are improved user comfort and / or a reduced likelihood of the device falling out during eyelid movement.

[0425] In some embodiments, the ophthalmic device is elongated. Here, for example, in some embodiments, the dimensions of the device measured along the long axis are about 0.5 mm to 20 mm. In some embodiments, the ophthalmic device is designed to be inserted into and removed from the eye by the patient wearing it. In some such embodiments, the device has a length of at least 3 mm along its short side so that the user can see and conveniently manipulate it when placing the device under the eyelid. In some such embodiments, the dimensions of the device measured along the long axis are greater than 3 mm, for example, at least 4 mm or at least 5 mm. On the other hand, the device is preferably not too large so as not to irritate the wearer, and therefore the maximum range may be about 8 mm in some embodiments. Here, in some embodiments, the range of the device is measured as the maximum dimension of the smallest rectangular parallelepiped shape in which the device fits. In some embodiments, for example, in relation to a low curvature of the device surface, the rectangular parallelepiped boundary shape is thinner in one dimension (for example, related to the orientation towards the eye when the device is over the eye) than in the other two dimensions.

[0426] In some embodiments, the body of the ophthalmic device is not hollow. In some embodiments, the body of the ophthalmic device is made from a continuous material, i.e., it does not contain macroscopic gaps and / or empty areas inside. In some embodiments, gaps or empty areas are defined as macroscopic if they are greater than 0.2 mm. In some embodiments, the body of the ophthalmic device is symmetrical with respect to its longitudinal axis (roughly indicated by line AA) and its transverse axis (roughly indicated by line BB), as shown, for example, in Figure 6A. For example, when the ophthalmic device 600 is viewed from the front, the device is symmetrical with respect to its longitudinal axis (AA) and its transverse axis (BB). In some embodiments, for example, in the embodiment schematically shown in Figure 6A, the symmetry with respect to both axes is mirror symmetry. In some embodiments, the device has an elliptical and / or oval cross-sectional shape. A potential advantage of the symmetry of the ophthalmic device is ease of use, where, in some embodiments, the device is applied by the user themselves, and the absence of "wrong" orientation can improve ease of use.

[0427] In some embodiments, the ophthalmic devices described herein may be used once to deliver a pharmaceutically active ingredient (API) and / or to provide availability of the API for a longer period than that of topical formulations such as eye drops, which are typically available for less than one minute. In some embodiments, drug delivery is provided for a period of about five minutes or more, or more than ten minutes, or more than one hour, or more than one day. Here, in some embodiments, the device functions as a sustained-release vehicle for one or more pharmaceutically active ingredients (APIs).

[0428] A potential advantage of ophthalmic devices configured to remain on the ocular surface is, for example, the potential extension of the retention time of therapeutic agents in the eye compared to topical compositions applied periodically (e.g., eye drops, ointments). A potential advantage of ophthalmic devices that release drugs while remaining on the ocular surface is the ability to provide and / or maintain an appropriate concentration of the drug in the precorneal / prescleral tear film for extended periods, such as from 5 minutes to 24 hours or more. A potential advantage of ophthalmic devices that release drugs while remaining on the ocular surface, for example, while being maintained in place on the ocular surface, is the potential ability of the drug to diffuse through ocular tissue. For example, it can penetrate the sclera and / or cornea and / or eyeball and / or reach more internal parts (may be more) of the eye. Potentially, in some embodiments, this allows for topical administration to areas typically treated by injection, e.g., into the inside of the eyeball. The potential advantages of ophthalmic devices (e.g., those with extended retention and / or elution times) are their ability to deliver and / or maintain appropriate concentrations of drugs to intranasal regions (which may include multiple regions) and / or the brain and / or head and / or other target organs, and / or systemically, as part of drug delivery.

[0429] In some embodiments, ophthalmic devices with retention allow for steady dissolution of therapeutic materials into the eye, thereby potentially reducing the effects of periodic administration of eye drops or ointments, such as temporary systemic and / or local overdose (potentially associated with a high risk of side effects) and prolonged periods of sub-thermal levels between doses. Here, the rate of tissue drug uptake is high in the early stages after administration but declines rapidly. Longer retention times compared to eye drops applied to the surface of the eye, e.g., the eyeball, for example, limit the time that liquid medication remains effective to, for example, a few minutes, due to the combined effects of blinking and natural tear flow. Potentially, in the treatment of subjects using ophthalmic devices, less active pharmaceutical ingredient (API) is used per treatment compared to topical formulations, which may result in a lower likelihood of high patient compliance due to frequent application, requiring larger amounts of API, and / or leading to more wasted unused API. In some embodiments, ophthalmic devices protect a portion of the eye from, for example, external impacts (may be multiple) and / or chemical changes, thereby improving and / or mitigating eye damage during, for example, orbisculation (squirting of citrus fruit juice into the eye). In some embodiments, ophthalmic devices protect a portion of the eye and allow that portion to heal. For example, in some embodiments, an eye incision and / or wound is closed and / or covered by placing an ophthalmic device over the incision. Here, the suction force between the eye surface and the device potentially assists in the closure and / or maintenance of the incision and / or wound, potentially accelerating healing.

[0430] In some embodiments, the device is tailored to individual subjects, where, for example, in some embodiments, one or more of the following are selected on an individual basis and / or according to an individual treatment plan: size, shape, surface curvature (may be multiple), type of therapeutic agent, release time, residence time. Throughout this specification, ophthalmic applications of the device are described, but it should be understood that one or more embodiments and / or combinations of embodiments of the device described herein are used in some embodiments for the treatment of other parts of the human or animal body. For example, parts of the eye other than the sclera, e.g., the cornea, the fornix of the eye; for example, other mucosal surfaces (may be multiple), e.g., the oral cavity, e.g., the nasal cavity surface; for example, other tissue types and / or organs. Throughout this specification, ophthalmic applications of the device are described, but it should be understood that one or more embodiments and / or combinations of embodiments of the device described herein are used in some embodiments for other applications, e.g., for housing, including, attaching, and / or providing supports for one or more types of electronic devices, e.g., electronic devices on the eye. For example, one or more active electronic elements and / or passive modules and / or components, such as an antenna or RFID. For example, one or more capacitors and / or resistors and / or shape memory elements, or which may function as a support for one or more other elements such as an eye region. Here, for example, in some embodiments, the electronic device includes one or more sensors (which may be multiple) (e.g., thermosensors, pressure sensors, moisture sensors), imaging devices (which may be multiple) (e.g., cameras), user interfaces, processors, transmitters, receivers, lighting elements, LED screens, and power supplies. In some embodiments, the electronic device (for example, using sensors (which may be multiple)) is used for treatment (e.g., electroconvulsive therapy (ECT)) and / or diagnosis. In some embodiments, one or more electronic components are used for entertainment (e.g., VR) and / or aesthetic enhancement. In some embodiments, the device is used for entertainment and / or aesthetic enhancement.In some embodiments, two or more devices described herein are used to treat a subject, for example, multiple devices are simultaneously in situ on the ocular surface, and each device provides a specific dose. Herein, in some embodiments, two or more devices are applied to provide a higher dose. In some embodiments, multiple devices described herein are provided packaged together and / or connected together. In some embodiments, the devices include and / or are constructed from non-toxic and / or biocompatible materials. In some embodiments, when the therapeutic material is toxic at high concentrations, the entire device includes, in some embodiments, a dose of the therapeutic material below a toxic dose and / or the device elutes the therapeutic material at a subtoxic level. In some embodiments, one or more parts of the device include dyes and / or pigments for ease of identification, for example, in the eye, and / or during insertion and / or removal, and / or during manufacturing. In some embodiments, the dyes and / or colors are printed in one or more identifying shapes and / or letters and / or numbers and / or barcodes. In some embodiments, one or more identifiers are embossed or engraved on the device. In some embodiments, the device includes one or more electronic identifiers, such as RFID, on or inside the body of the device. In some embodiments, the dyes and / or pigments of the device include one or more of blue, red, fluorescent yellow, and / or any other color. In some embodiments, the ophthalmic device is manufactured from a film, such as a multilayer film. Here, in some embodiments, the film is cut into shape to form individual devices. In some embodiments, the film and / or individual devices are shaped, for example, to form a desired curvature of the surface. Here, in some embodiments, shaping is done by casting a solution onto a shaped support surface, such as a mold. Here, in some embodiments, shaping is done by mechanical and / or chemical treatment, such as the application of pressure and / or heat.Therefore, in some embodiments, an ophthalmic device can be obtained by mixing the API with water and an ophthalmic lubricant to obtain a mother liquor, and optionally drying the mother liquor at room temperature in a mold shaped according to a desired shape of the device. In some such embodiments, the ophthalmic device can be obtained without heating the mother liquor. In some embodiments, the ophthalmic device can be obtained without heating the API. In some embodiments, the pharmaceutically active ingredient(s) (API) is incorporated into one or more solutions that are continuously cast onto a support surface to provide a multilayer film. In some embodiments, the separately cast layers have one or more different properties (e.g., thickness, mucosal adhesion, lubricity, pharmaceutically active ingredient(s) (API)). In some embodiments, one or more surfaces are treated to impart different properties, for example, to make the surface more adhesive and / or more lubricating.

[0431] Before describing in detail at least one embodiment of the present invention, it should be understood that the present invention is not necessarily limited in its application to the details of the arrangement and / or method of configurations and components described in the following description and / or shown in the drawings and / or described in the embodiments. Other embodiments of the present invention are possible, or it can be carried out or implemented in a variety of ways.

[0432] table of contents 1. Introduction of Disclosure 2. Exemplary forms / geometric shapes 2.1 Exemplary Usage 2.2 Exemplary Detailed Method 2.3 Exemplary Ophthalmic Devices 2.4 Exemplary Decomposition 2.5 Exemplary Treatment Methods 2.6 Exemplary Materials 2.6.1 Exemplary Lubricating Materials 2.6.2 Exemplary mucosal adhesive materials 2.6.3 Exemplary therapeutic materials 2.6.4 Exemplary Nanoparticles and / or Microparticles as Active Pharmaceutical Ingredients (APIs) 2.7 Overview of Exemplary Forms / Geometric Shapes 3. Exemplary elastomer matrix containing PVOH 3.1 Exemplary Elastomer Matrix 3.2 Exemplary Mechanical Properties 3.3 Exemplary Plasticizers 3.4 Exemplary Composition of Elastomer Matrix 3.5 Exemplary Composite Elastomer Matrix 3.6 Exemplary medical / ophthalmic devices 3.7 Exemplary Treatment Methods 3.8 Exemplary preparation method 3.9 Overview of Exemplary Elastomer Matrix Containing PVOH 4. Exemplary elastomer matrix containing two or more types of PVOH 4.1 Exemplary Basic Composition of Exemplary Elastomer Matrix 4.2 Exemplary degrees of hydrolysis (DH), degree of polymerization (DP), decomposition time, and combinations thereof 4.3 Exemplary amounts of components in an exemplary elastomer matrix composition 4.4 Exemplary Mechanical Properties 4.5 Exemplary Plasticizers 4.6 Exemplary Composite Elastomer Matrix 4.7 Exemplary medical / ophthalmic devices 4.8 Exemplary Treatment Methods 4.9 Exemplary preparation method 5. Additional illustrative information regarding exemplary ophthalmic devices 5.1 Exemplary composition of an exemplary ophthalmic device 5.2 Exemplary Process for Manufacturing Exemplary Ophthalmic Devices 5.3 Exemplary Shapes of Exemplary Ophthalmic Devices 6. Exemplary use of ophthalmic devices in the treatment of presbyopia 6.1 Introduction 6.2 Exemplary active pharmaceutical ingredients (APIs) for treating presbyopia 6.3 Exemplary preparation method for ophthalmic devices containing active pharmaceutical ingredients (APIs) for the treatment of presbyopia 6.4 Exemplary Potential Benefits of Using Exemplary Ophthalmic Devices for the Delivery of Active Pharmaceutical Ingredients (APIs) 6.5 Illustrative general mechanisms of action of ophthalmic devices in the treatment of presbyopia 6.6 Exemplary preliminary clinical results 7. Exemplary use of an ophthalmic device in the treatment of dry eye. 7.1 Introduction 7.2 Illustrative general mechanisms of action of ophthalmic devices in the treatment of dry eye 7.3 Exemplary Potential Benefits of Using Exemplary Ophthalmic Devices for the Treatment of Dry Eye 7.4 Comparison of exemplary lubricant content between exemplary ophthalmic devices and typical over-the-counter (OTC) eye drops

[0433] 1. Introduction of Disclosure In some embodiments, the present invention relates to ophthalmic devices fabricated from an elastomer matrix having a specific composition and form (or geometric shape).

[0434] In the following chapters, exemplary embodiments of morphology (geometric shapes) are described in Chapter 2, followed by exemplary embodiments of elastomer matrices and their compositions in Chapters 3 and 4. Several exemplary ophthalmic devices including elastomer matrices shaped as described in Chapter 2 and configured as described in Chapter 3 or 4 are described in Chapter 5, however all morphology or geometric shapes described in Chapter 2 can be fabricated with elastomer matrices configured as described in Chapters 3 and 4, even if not explicitly described in Chapter 5.

[0435] Chapters 6 and 7 describe exemplary uses of the ophthalmic devices described in Chapters 2 through 5. Chapter 6 describes the use of such devices for the treatment of presbyopia, and Chapter 7 describes the use of such devices for the treatment of dry eye disease (also known as dry eye syndrome).

[0436] 2. Exemplary geometric shapes / shapes of exemplary ophthalmic devices The following paragraphs disclose exemplary geometric shapes / shape characteristics of exemplary ophthalmic devices.

[0437] 2.1. Exemplary Usage Referring here to Figure 1, several embodiments of the present invention illustrate how to use an ophthalmic device. The ophthalmic device described in Chapter 2 may be configured as described in Chapter 3 or Chapter 4, or, for example, as described in Chapter 5.

[0438] In some embodiments of 100, the ophthalmic device is placed inside the eye. For example, it is placed on the surface of the eye, for example, on the conjunctiva and / or on a portion of the sclera.

[0439] In 102, in some embodiments, the ophthalmic device dissolves the drug into the eye.

[0440] In 104, in some embodiments, the ophthalmic device exits the eye. Here, in some embodiments, the device is removed and / or ejected by the eye manually (e.g., by the user or caregiver). Here, in some embodiments, before the ophthalmic device exits, the device disintegrates / breaks down at least partially. In some embodiments, exiting the eye includes one or more features, which are one or more of steps 514 to 524 in Figure 5.

[0441] Referring now to Figure 2, several embodiments of the present invention illustrate treatment methods using ophthalmic devices.

[0442] In some embodiments of 200, the ophthalmic device is positioned on the conjunctiva of the eyeball and at least partially below the eyelid, for example, entirely below the eyelid. Here, in some embodiments, the holding portion of the ophthalmic device is positioned adjacent to the opening of the eyelid and deeper in the conjunctival sac than the tarsal plate of the eyelid, for example, when the eyelid is opening and closing.

[0443] In 202, in some embodiments, the interaction between the retaining portion, the eyelid, and / or the eyeball prevents the ophthalmic device from slipping out from under the eyelid. In some embodiments, the interaction between the tarsal plate of the eyelid and the tilt and / or height of the device acts to hold the device within the eyelid, behind the tarsal plate. In some embodiments, the interaction between the tarsal plate and the device is related to the deformation of the eyelid tissue around the device. In some embodiments, alternatively or additionally to the force of the tarsal plate, the tissue reaction force due to the deformation of the eyelid acts on the device to prevent movement of the device, e.g., out of the eyelid and / or deep into the fornix of the eye. Alternatively or additionally, in some embodiments, the force between the eyeball and the posterior surface of the device acts to prevent movement of the device, where, in some embodiments, the force includes the reaction force of the eyelid pressure on the device and then on the eyeball, and / or the attractive force between the device and the eyeball.

[0444] Referring to Figure 3A, a simplified schematic cross-section of the eye is shown.

[0445] Referring also to Figure 3B, a simplified schematic cross-sectional view of an ophthalmic device 300 positioned on the eye surface when the eye is closed is shown according to several embodiments of the present invention.

[0446] Referring also to Figure 3C, a simplified schematic cross-sectional view of an ophthalmic device 300 positioned on the eye surface when the eye is open is shown according to several embodiments of the present invention.

[0447] In some embodiments, the cross-sectional views in Figures 3A to 3C are taken in the top-to-bottom direction, for example, sagittal cross-sections of an eye.

[0448] In some embodiments, the device 300 is covered by the lower eyelid 346 when the eye is closed (Figure 3B) and when the eye is naturally open (Figure 3C). In some embodiments, the device 300 is positioned close enough to the eyelid opening, for example, on the conjunctiva of the eyeball, not too deep in the direction of the fornix, and sufficient for manual movement of the eyelid (for example, without causing discomfort to the user) to expose the device at least partially.

[0449] In some embodiments, the device 300 is positioned on the ocular surface, which is part of the conjunctival surface around the eyeball 308. In some embodiments, the ophthalmic device 300 is located in the conjunctival portion of the sclera, which is the conjunctival region between the conjunctival fornix 340 and the cornea 302, adjacent to the cornea.

[0450] In some embodiments, the device 300 has a body including a rear surface 316 and a front surface 318. In some embodiments, the device 300 has a retaining portion 336, which, in some embodiments, is part of the device 300 adjacent to the opening 350 of the eyelid 346. In some embodiments, the retaining portion 336 is sufficiently thick and / or slopes sufficiently steeply with respect to the eyelid 346 at a short distance from the front edge 366 of the device 300, and the device 300 is held below the eyelid 346, for example, by a tarsal plate 348. In some embodiments, the body of the ophthalmic device is not hollow. In some embodiments, the body of the ophthalmic device is made of a continuous material, i.e., it does not contain macroscopic gaps and / or empty areas inside. In some embodiments, gaps or empty areas are defined as macroscopic if they are greater than 0.2 mm. While a description of the ocular surface has been provided, it should be understood that, in some embodiments, the posterior and anterior surfaces are distinct from each other, regardless of whether they are on the inside or outside of the eye, as described above. In some embodiments, the posterior and anterior surfaces have different shapes (for example, one is convex and the other concave, one is curved and the other is flat, etc.).

[0451] In some embodiments, the retaining portion 336 includes one or more features, which are one or more of the retaining portions 636 (Figures 6A and 6B), 736 (Figure 7), 1336 (Figures 13A to 13C), 1436 (Figure 14), 1536 (Figures 15A to 15D), and / or other retaining portions (which may be more) described elsewhere in this specification.

[0452] In some embodiments, reaction forces associated with the deformation of the eyelid 346 and / or conjunctiva 308 around the device 300, and / or interactions between the tarsal plate 348 and the retaining portion 336, act to hold the device 300 in place on the ocular surface and / or below the eyelid 346.

[0453] Referring now to Figure 3D, a simplified schematic top view of an ophthalmic device 300 positioned on the eye surface according to several embodiments of the present invention is shown.

[0454] In some embodiments, as shown in Figure 3D, for example, the ophthalmic device 300 is positioned on the ocular surface (e.g., the sclera), for example, in the lower portion of the conjunctiva below the lower eyelid 346, for example, entirely beneath the lower eyelid 346.

[0455] Referring now to Figure 4A, a simplified schematic top view of an ophthalmic device 400 positioned on the eye surface 404 according to several embodiments of the present invention is shown.

[0456] In some embodiments, as shown in Figure 4A, for example, the ophthalmic device 400 is positioned on the ocular surface 404 (e.g., the sclera), for example, in the upper portion of the conjunctiva below the upper eyelid 444, for example, entirely below the upper eyelid 444. In some embodiments, when the device 400 is positioned in the upper portion of the eye, the position is deeper within the fornix (compared to, for example, a position where the device is positioned in the lower portion of the eye, for example, below the lower eyelid).

[0457] Referring now to Figure 4B, a simplified schematic cross-sectional view of an ophthalmic device 400 positioned on the eye surface 404 when the eye is closed, according to several embodiments of the present invention.

[0458] In some embodiments, the ocular surface 404 is the upper portion of the sclera. In some embodiments, the device is held, for example, under the upper eyelid 344 when the eye is opening and closing.

[0459] In some embodiments, the depth to which the device 400 is inserted, and / or the length of the device extending below the upper eyelid, is greater than that of a device used below the lower eyelid. In some embodiments, the device is more likely to remain below the upper eyelid, where the eyelid and tarsal plate have a larger area.

[0460] In some embodiments, reaction forces associated with the deformation of the eyelid 444 and / or conjunctiva 408 around the device 400, and / or the interaction between the upper tarsal plate 462 and the retaining portion 436, act to hold the device 400 in place on the ocular surface and / or below the upper eyelid 444.

[0461] Referring here to both Figure 3D and Figure 4A, arrows 360 and 460 indicate the exemplary positional ranges of devices 300 and 400, for example, with respect to the visible portion of the eye.

[0462] In some embodiments, the ophthalmic device 300 is positioned below the central portion of the lower eyelid 346. In some embodiments, the ophthalmic device 400 is positioned below the central portion of the upper eyelid 444.

[0463] For example, when measured along the contour of the junction between the eyelid and the ocular surface (e.g., sclera 304, 404), the measurement is, for example, 2mm to 10mm or 2mm to 7mm in the center.

[0464] For example, measured along the contour of the junction between the eyelid and the ocular surface (sclera 304, 404 and / or cornea 302, 402), it is, for example, at least 1 mm, 2 mm, or 5 mm from the medial and / or lateral canthus.

[0465] For example, the central portion is 30% to 80%, or 40% to 70%. Here, in some embodiments, this portion is measured as the length along the contour of the eyelid (e.g., at the junction between the eyelid and the ocular surface) relative to the total length measured along the contour of the eyelid between the canthal corners when the eye is closed and / or open.

[0466] In some embodiments, the devices 300, 400 are symmetrical in shape in, for example, one or more dimensions. In some embodiments, the devices 300, 400 have a circular footprint when present on, for example, the ocular surface (e.g., the sclera 304, 404).

[0467] 2.2. Exemplary Detailed Method Referring now to Figure 5, several embodiments of the present invention illustrate how to use an ophthalmic device.

[0468] In some embodiments of 500, the substance is optionally applied to the eye and / or an ophthalmic device.

[0469] For example, in some embodiments, the device is stored in a dry or partially hydrated form and is hydrated before use (e.g., before insertion into the eye), for example, before placing the device on the surface of the eye, by applying water and / or a hydration solution to the device. In some embodiments, the device is immersed in a hydration solution for, for example, 5 seconds to 20 minutes, before being applied to the eye. In some embodiments, the device is humidified for, for example, 1 minute to 2 hours, by exposure to moist air and / or gas, before being applied to the eye.

[0470] In some embodiments, one or more therapeutic materials are applied to the device. In some embodiments, a mucosal adhesive material and / or a lubricating material is applied to the device, for example, one or more parts of the device.

[0471] In 502, in some embodiments, the ophthalmic device is applied to the ocular surface. In some embodiments, the application includes bringing the device into contact with the ocular surface, for example, the sclera, for example, the conjunctiva of the eyeball.

[0472] In some embodiments, the application involves pulling back the eyelid to which the device is placed, typically positioning the device on the ocular surface below the eyelid.

[0473] In some embodiments, the device is applied directly and / or manually to the eye surface, for example, by the patient themselves. In some embodiments, a caregiver applies the device. Optionally, in some embodiments, the device is applied using an applicator.

[0474] In some embodiments, for example, if the device is not rotationally symmetric, the device is oriented before and / or during placement on the ocular surface. In some embodiments, the applicator is sized and / or shaped and / or has one or more indicators to help position the device in a desired orientation within the eye. The orientation is, for example, an orientation with respect to the anterior edge and / or shape (e.g., elongated) of the device, as described elsewhere in this specification.

[0475] In 504, optionally, in some embodiments, after application to the ophthalmic surface, the ophthalmic device is repositioned, for example, by manipulation of the eye and / or the ophthalmic device and / or the eyelid. For example, in some embodiments, the ophthalmic device is positioned to protrude at least partially from below the eyelid, and in some embodiments, the ophthalmic device is repositioned (for example, so that it is completely below the eyelid) by directly moving the ophthalmic device and / or by manipulating the eye (e.g., the eyelid) to move the ophthalmic device. For example, in some embodiments, the ophthalmic device is positioned on the sclera above the eyelid and then manipulated downward until, for example, it is covered by the eyelid and / or held in place by the tarsal plate. In some embodiments, the attractive force between the device (e.g., the posterior surface of the device) and the ophthalmic surface is low, at least initially, to allow for the repositioning of the device. Although a description has been given with respect to the ophthalmic surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the rear and front surfaces have different shapes (for example, one is convex and the other concave, one is curved and the other is flat, etc.).

[0476] In 506, in some embodiments, the ophthalmic device is held in place by the anatomical structure of the eye as the device is fitted and the eye rotates. For example, it is held, for example, under the eyelid by an interaction between the tarsal plate and the retaining portion of the device, including one or more features illustrated and / or described with respect to device 300, tarsal plate 348 (Figures 3B and 3C) and / or device 400, tarsal plate 462 (Figure 4B).

[0477] In some embodiments of 508, optionally, the device hydrates in the eye and, for example, absorbs tear fluid.

[0478] In 510, optionally, in several embodiments, the ophthalmic device is attached to the surface of the eye.

[0479] In some embodiments, adhesion is related to the pressure between the ophthalmic device (e.g., the posterior surface of the device) and the ocular surface. In some embodiments, the curvature of the posterior surface of the ophthalmic device helps the device adhere to the ocular surface. In some embodiments, this adhesion is amplified by the pressure of the eyelid on the device. In some embodiments, one or more sharp edges of the device help the device adhere to the ocular surface. In some embodiments, for example, one or more recesses and / or protrusions on the posterior surface of the device help the adhesion.

[0480] In some embodiments, when the device is applied to the ocular surface (i.e., in situ), the device adheres to the ocular surface due to the material properties of the mucosal adhesive layer of the device at the time of application and / or after the properties of the mucosal adhesive layer have changed in situ (e.g., after hydration).

[0481] In exemplary embodiments, the adhesion of the ophthalmic device to the ocular surface is sufficient to keep the device on the ocular surface (e.g., the sclera) for a short period, e.g., less than 10 minutes, e.g., 1 minute to 1 hour, e.g., during blinking, e.g., several blinks, e.g., 1 to 10 blinks, or 1 to 100 blinks, if the device slips away from under the eyelid. Meanwhile, in some embodiments, the user returns the device under the eyelid according to one or more features, e.g., described with respect to step 504.

[0482] In some embodiments of 512, the device remains on the eyeball for a certain period of time. For example, it remains under the eyelid.

[0483] In some embodiments, the device is maintained in situ (in the eye) for at least 1 minute, or 1 to 10 minutes, or at least 0.5 hours, or 0.1 to 2 hours, or 2 to 8 hours, or more than 8 hours, or 8 to 24 hours, or 1 to 7 days, or 7 days to 1 month, or 1 to 3 months, or 3 months to 1 year, or 1 to 30 days, or 1 month to 1 year.

[0484] In some embodiments, the device remains in situ (residence time) and / or is maintained and is discharged and / or removed from the eye less than approximately 24 hours after administration. Here, in some embodiments, discharge and / or removal removes the device from the eye, cleansing the eye (e.g., without leaving any debris) and preparing the eye for additional administration, e.g., additional device administration.

[0485] In 514, optionally, in some embodiments, one or more parts of the device disassemble and / or collapse.

[0486] In some embodiments, device degradation occurs by one or more of the following: mechanical degradation (e.g., movement of the eyeball or eyelid), chemical degradation (e.g., tear fluid), or biological degradation (e.g., enzyme activity).

[0487] In some embodiments, the disintegration rate is increased by the user, for example, in some embodiments, pressure is applied to the device (e.g., manually) to break the device into two or more parts and / or to accelerate such breakage. In some embodiments, once broken into two or more parts, one or more of the parts are resized and / or shaped to remain under the eyelid (e.g., having retaining parts).

[0488] In some embodiments, the device includes parts that disassemble at different speeds. For example, it includes one or more features illustrated and / or described with respect to A and B in Figure 28 and / or Figure 29 and / or Figure 30.

[0489] In some embodiments of 516, the device performs a treatment, for example, by eluting a drug into the eye. In some embodiments, elution is related to the breakdown of the eluting portion(s) of the device.

[0490] In 518, optionally, in some embodiments, one or more parts of the device collapse. For example, a part of the device collapses to expose a therapeutic material and / or additional therapeutic material. In some embodiments, a part(s) of the device associated with device adhesion, such as a mucosal adhesive layer, such as a part that contributes to mechanical adhesion, such as a part(s) of the device edge and / or a part(s) that changes the curvature of one or more surfaces of the device collapses.

[0491] In 520, optionally, in some embodiments, the device disintegrates. For example, the device disintegrates mechanically, reducing the device's adhesion to the eye and / or reducing the device's size and / or shattering the device. In some embodiments, the entire device disintegrates after remaining on the ocular surface for a period of about 0.1 hours to 1 year, or less than 0.1 hours (e.g., immediately after placement on the eye, e.g., within 1 minute).

[0492] In 522, in some embodiments, the ophthalmic device and / or parts(s) of the ophthalmic device are ejected naturally from the eye, for example by eyelid and / or eyeball movement and / or blinking and / or tearing. In some embodiments, the device is ejected using eyelid manipulation. In some embodiments, parts of the device are ejected (for example, when step 520 occurs). In some embodiments, for example, if the device remains in part, for example, during the disintegration of adhesive-related parts(s) of the device, the device is ejected naturally.

[0493] In 524, optionally, in some embodiments, the ophthalmic device and / or parts (or parts) of the device are removed, for example, manually, by the application of mechanical force, such as pinching and / or suction, and / or during the use of a removal device (e.g., a suction cup, forceps) and / or by rinsing the eye.

[0494] In some embodiments, ophthalmic devices are removed by a combination of manual and natural processes. For example, in some embodiments, pressure is applied to the device to break it into two or more fragments, or to accelerate such breakage. Here, in some embodiments, one or more of the fragments are then naturally discharged and / or dissolved.

[0495] In some embodiments, one or more additional therapeutic methods are performed incidentally, sequentially, or simultaneously with and / or between one or more steps of the described methods of steps 500 to 524. For example, in some embodiments, a topical drug is applied, for example, during the residence time of the device on the ocular surface.

[0496] 2.3. Exemplary Ophthalmic Devices Referring now to Figure 6A, a simplified schematic top view of an ophthalmic device 600 positioned on the ocular surface 604 below the eyelid 646 according to several embodiments of the present invention.

[0497] In some embodiments, the device 600 includes a retaining portion 636, which is formed by a portion of the device 600 adjacent to the opening of the eyelid 646 when the device is in place on the ocular surface (wherein some embodiments the eyelid 646 is the lower eyelid).

[0498] In some embodiments, the retaining portion 636 is a part of the device 600 that extends inward from the leading edge 666 of the device (for example, toward the center of the device 600).

[0499] In some embodiments, the retaining portion 636 extends inward from the leading edge 666 by at least a portion 630 of the depth 620 of the device 600. In some embodiments, the retaining portion 636 extends laterally, for example, along the leading edge 666, by at least a portion of the lateral length 622 of the device 600.

[0500] Referring now to Figure 6B, a simplified schematic cross-sectional view of an ophthalmic device 600 according to several embodiments of the present invention is shown.

[0501] Figure 6B shows a cross-section of device 600 of Figure 6A, where the cross-section is taken along line BB of Figure 6A. Figure 6B shows, for example, the range of the cross-section of device 600 parallel to line BB of Figure 6A for the entire lateral range 628 of the retaining portion 636. Figure 6B shows each of the ranges of the cross-section of device 600 of Figure 6A where the cross-section is along line BB of Figure 6A or parallel to line BB of Figure 6A.

[0502] In some embodiments, the body of the ophthalmic device 600 is symmetrical with respect to its longitudinal axis (approximately indicated by line AA) and its transverse axis (approximately indicated by line BB). For example, when the ophthalmic device 600 (or other ophthalmic devices, e.g., 300, 400, 800, 900, 1300, 1400, 1500, 1600, 1700, 1900, 2000, 2500, 2600, 2700, 2900, 3000, 3100) is viewed from the front, the device is symmetrical with respect to its longitudinal axis (AA) and its transverse axis (BB). In some embodiments, the device 600 has a front surface 618 and a rear surface 616. In some embodiments, the device 600 is a volume between surfaces 616, 618, and is curved, for example, so that one or both surfaces are in contact with the other surface. For example, as shown in Figure 6B, the anterior surface 618 is curved so as to be in contact with the posterior surface 616. In some embodiments, when present on the ocular surface, the posterior surface 616 is adjacent to the ocular surface (e.g., the sclera). In some embodiments, when present on the ocular surface, the anterior surface 618 is adjacent to the conjunctiva of the eyelid (e.g., the lower eyelid). In some embodiments, the anterior surface 618 is convex and / or has a convex portion. In some embodiments, the posterior surface 616 is convex and / or has a convex portion, as schematically shown by the dotted line 616a in Figure 6B. Although an explanation has been given with respect to the ocular surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other is concave, one is curved and the other is flat, etc.).

[0503] In some embodiments, the retaining portion 636 has a retaining height 662 located at a retaining distance 664 from the leading edge 666. Here, in some embodiments, the retaining height 662 is maintained (or exceeds) a length 632 extending from the leading edge toward the trailing edge 634.

[0504] In some embodiments, the retaining portion 636 has a concave and / or sufficiently steep incline 614 (defined, for example, by the incline of the front surface 618) toward the retaining height 662 from the front edge 666. Hereinafter, in some embodiments, at a first distance 652 from the front edge 666, the device 600 has a first height 654, and / or at a second distance 656 from the front edge 666, the device 600 has a second height 658. In some embodiments, the second distance 656 is a maximum of 1 mm and the first distance 652 is at least 1 mm.

[0505] Here, the distance from the leading edge 666 is measured along the front surface and / or along the surface described with respect to height measurements (e.g., elsewhere in this specification).

[0506] In some embodiments, the angle θ of the inclination of the front surface 618 at the front edge 666 or the edge of the retaining portion (e.g., the angle of the tangent to the surface at the front edge) is at least 35°, or at least 46°, or 46° to 90°, or 46° to 86°, or 46° to 70°, or a lower, higher, or intermediate angle or range. Here, in some embodiments, the angle is measured with respect to the plane on which the device is mounted in a relaxed configuration. Here, in some embodiments, the angle is measured with respect to the ocular surface, e.g., the angle of the ocular surface at the front edge 666 and / or the edge of the retaining portion.

[0507] In some embodiments, the front surface 618 has a radius of curvature 624 extending from the leading edge 666 to the retaining height 662. Here, in some embodiments, the radius of curvature 624 is equal to, for example, the peak height of the device measured between the rear surface 616 and the front surface 618 of the device 600.

[0508] In some embodiments, the device cross-section (with respect to one or more cross-sections) is symmetrical, for example, having mirror symmetry, as shown in Figure 6B. In some embodiments, the device is symmetrical in at least one direction, for example, with respect to line BB and / or line AA shown in Figure 6A.

[0509] In some embodiments, the ophthalmic device 600 is elongated. Here, in some embodiments, the length 622 of the device 600 is greater than the width 620 of the device 600. In some embodiments, the length 622 is 1.5 to 10 times greater.

[0510] A potential advantage of the elongated device is that the longer sides 666, 634 of the device provide an increased surface area for, for example, retention of the device within the eyelid and / or interaction with the eyelid(s) when removing the device using pinch removal.

[0511] In some embodiments, the device 600 is positioned below the eyelid 646, where the longitudinal direction of the device 600 is aligned with the eyelid contour, e.g., along the contour of the opening to the eyelid 646 and / or along the contour of the tarsal plate 648 of the eyelid 646. A potential advantage of the device 600 being elongated is the increased length of interaction between the device and the eyelid, e.g., the tarsal plate (e.g., compared to the length of interaction of a less elongated device of the same volume and / or footprint size). In some embodiments, a potential advantage of the device being elongated is the reduced possibility of device rotation in situ. In some embodiments, the length 622 is greater than the depth of the fornix of the eye, potentially preventing, for example, the device 600 from rotating so that its longitudinal direction extends from the eyelid opening to the bottom of the fornix.

[0512] In some embodiments, the width 620 and / or length 622 of the device 600 is 2 mm to 10 mm. For example, in some embodiments, the length 622 is 5 mm to 10 mm, and / or the width 620 is 3 mm to 5 mm, and / or the height 662 and / or height 624 is 2 mm to 2.5 mm. In some embodiments, the holding height 662 is at least 2 mm at a distance 664 of 2 mm from the leading edge 666. Alternatively or additionally, in some embodiments, the height 654 is at least 1.3 mm at a distance 652 of 0.5 mm. Alternatively or additionally, in some embodiments, the height 658 is at least 1.7 mm at a distance 656 of 1 mm.

[0513] In some embodiments, when the distance 664 is 2 mm, the height 662 is greater than or less than 0.5 mm to 5 mm, or 0.5 mm to 2 mm, or 1 mm to 2 mm, or is in an intermediate or higher height or range.

[0514] In some embodiments, the retaining height 662 is maintained over a cross-sectional area, for example, a length 632 which is at least 1 mm.

[0515] In some embodiments, the peak height 624 is a maximum of 5 mm, or 4 mm, or about 3 mm, or about 2 mm.

[0516] In some embodiments, the front surface 616 is curved, for example, concave, as described elsewhere in this specification. This includes, for example, one or more features which are one or more of the devices 1300 (Figures 13A-13C), device 1400 (Figure 14), and / or other devices (may be more than one) described elsewhere in this specification.

[0517] In some embodiments, the device 600 is sufficiently rigid and / or resistant to forces (e.g., suction forces) when it is over the eye, so that the device does not deform significantly within the eye, the height described above is one or more of the following heights: A plane on which a relaxed device is placed, A plane connecting the peripheral edge of the device or a large portion of the circumference of the device (e.g., at least 80%, or at least 90%, or at least 95%, or at least 99%) A curved surface on which a relaxed device is placed, for example, a surface having curvature in one or more directions of the eyeball, for example, a sphere having the radius of curvature of the eyeball.

[0518] In some embodiments, the distance measured from the front edge 666 is measured along a plane used for measuring the height, and / or along the rear surface, and / or along the front surface, and / or along planes equidistant between the surfaces.

[0519] In some embodiments, the height described with respect to one or more of, for example, 654, 658, 662, and 624, is the height of the device in situ from the ocular surface. Here, in some embodiments, the front surface 616 is curved (e.g., concave or convex). In some embodiments, forces on the device (e.g., attractive forces between the device and the eyeball and / or pressure from the eyelid onto the device via the front surface) act to flatten the device when it is in situ on the ocular surface.

[0520] Alternatively, the height described is that of a relaxed device, where, in some embodiments, the flattening of the device reduces one or more heights of the device by up to 30%, or up to 5% to 50%, or up to 5% to 30%, or up to 5% to 20% from their original heights. For example, a height reduction of up to 30% corresponds in some embodiments to the maximum height being at least 70% of the original (pre-flattening) maximum height after flattening.

[0521] Referring now to Figure 7, a simplified schematic cross-sectional view of a part of the device according to several embodiments of the present invention is shown.

[0522] Figure 7 shows exemplary front surfaces 714, 714b, and 714c of an exemplary device, where each of the front surface contours of the device has a retaining thickness 762 located at a retaining distance 764 from the leading edge 766 of the device. The convex front surface 714 (as described with respect to the front surface 618 of device 600 (Figure 6B)) is shown for comparative purposes with embodiments in which, for example, the contour 714c extending from the leading edge 766 to the retaining thickness 762 has a constant slope (e.g., within a certain 10%), and the contour 714b is concave.

[0523] Referring now to Figures 8 to 12, simplified schematic top views of devices 800, 900, 1000, 1100, and 1200 according to several embodiments of the present invention are shown.

[0524] The dashed lines represent the contour lines of the device's front surface, and for the front surface, the solid lines indicate the same distance above the height defined by the plane of the device's footprint shown in Figures 8 to 12.

[0525] In some embodiments, as shown in Figure 8, for example, the device 800 has the same slope and / or edge contour extending around the periphery of the device (or extending around at least 50%, 70%, or 90%) (for example, indicated by contour lines).

[0526] Here, for example, the frontal inclination 814 adjacent to the anterior edge 866 and the inclination 874 adjacent to the posterior edge 834 are the same. In some embodiments, the inclinations 876, 878 on the lateral side of the device are the same, for example, the same as each other and / or the same as inclinations 814, 874. A potential advantage is that the retaining force of the device on the device (e.g., of the eyelid on the device) is maintained (or changes little) when the device rotates (e.g., while the device is in place, e.g., under the eyelid). In some embodiments, the lateral inclinations 876, 878 of the device 800 are different, for example, to configure the device 800 in a direction along the changing anatomical structure of the eye, e.g., the contour of the eyelid.

[0527] In some embodiments, different edges of the device have different inclines, as shown, for example, in Figures 9 and 11. For example, in some embodiments, the inclines 914, 1114 of the retaining portion are located in the central region of the leading edges 966, 1166 of the device 900, 1100, where, in some embodiments, one or both of the lateral edges of the device have inclines 976, 978, 1176, 1178 with a lower gradient.

[0528] In some embodiments, for example as shown in Figure 10, the inclination 1074 on the front of the device extending to the trailing edge 1034 is higher than that of the retaining portion inclination 1014 adjacent to the leading edge 1066 of the device 1000.

[0529] In some embodiments, as shown, for example, in Figures 11 and 12, the regions of the device adjacent to the anterior edges 1166, 1266 accommodate the retaining portion, while the device inclinations 1174, 1274 extending toward the posterior edge have a lower gradient. A potential advantage is improved comfort due to the device tapering in the thickness direction as it extends further beneath the eyelid toward the apex of the conjunctival fornix. In some embodiments, one or both lateral sides of the device also have inclinations 1176, 1178 with a lower gradient than the retaining portion inclinations 1114.

[0530] Referring now to Figure 13A, a simplified schematic diagram of the ophthalmic device 1300 according to several embodiments of the present invention is shown. Figure 13A shows an isometric view of the ophthalmic device 1300. In some embodiments, the morphology of the ophthalmic device 1300 is dome-shaped or hemispherical. Referring also to Figure 13B, a simplified schematic cross-sectional view of the ophthalmic device 1300 according to several embodiments of the present invention is shown. Furthermore, referring to Figure 13C, a simplified schematic top view of the ophthalmic device 1300 according to several embodiments of the present invention is shown.

[0531] In some embodiments, the ophthalmic device 1300 has a front surface 1316 and a rear surface 1318. Here, in some embodiments, the front surface 1318 is curved so as to be in contact with the rear surface 1316 at the edge 1366 of the device 1300.

[0532] In some embodiments, the ophthalmic device 1300 is symmetrical with respect to, for example, one or more axes of symmetry. In some embodiments, as shown, for example in Figure 13C, the ophthalmic device 1300 is symmetrical with respect to line AA and / or line BB.

[0533] In some embodiments, the device 1300 has rotational symmetry, for example, with respect to a central axis 1370 extending through the center 1372 in the top view of the device, where the axis 1370 is perpendicular to one or both of the front 1318 and the rear 1316.

[0534] In some embodiments, the footprint of device 1300 (as shown, for example, in Figure 13C) has a diameter of 2 mm to 10 mm, or 3 mm to 8 mm, or 4 mm to 7 mm, or 5 mm to 6 mm. Here, in some embodiments, device 1300 has a height of 2 mm to 2.5 mm.

[0535] In some embodiments, the rear surface 1316 is curved in one or more directions, for example. For example, in some embodiments, Figure 13B shows a cross-section of the device taken along lines AA and / or BB in Figure 13C.

[0536] A potential advantage of symmetric (e.g., rotationally symmetric) devices is that when the device rotates in situ, the device properties with respect to, for example, the anatomical structure of the eye are maintained.

[0537] In some embodiments, although not shown in Figures 13A, 13B, or 13C, the front surface 1318 has a larger radius of curvature (RA - front surface radius) than the radius of curvature of the rear surface 1316 (RP - rear surface radius). Here, for example, in some embodiments, RA is 1.2 to 10 times or 1.2 to 5 times RP.

[0538] In exemplary embodiments, the radius of curvature of the front surface 1318 is equal to (or approximately equal to, e.g., within 20%, 10%, or 5%) the maximum thickness 1324 of the device 1300 (e.g., device 1300 having a hemispherical shape for the front surface 1318).

[0539] In exemplary embodiments, the device footprint (Figure 13C) and / or the radius of the edge 1366 (e.g., half the width 1320) is 0.5 mm to 10 mm, or 1 mm to 10 mm, or 1 mm to 5 mm, or 2 mm to 4 mm, or 2.5 mm to 3 mm.

[0540] A hemispherical device, as described with reference to Figures 13A-13C, with a diameter of 1320 x 5.5 mm, a concave posterior surface 1316, and a height of 1324a (measured when the device is in a relaxed configuration on a plane) of 2 mm, was placed on the sclera beneath the lower eyelid of human volunteers and remained comfortably in place for several hours.

[0541] A device with an elongated hemispherical shape, or a device that can also be defined as having an elongated elliptical hemispherical shape as described with respect to Figures 15A to 15D, having a concave posterior surface, a length of 1522 x 6 mm, a width of 1520 x 4 mm, and a height of 1524 x 2 mm, was placed on the sclera beneath the lower eyelid of a human volunteer's eye and remained comfortably in place for several hours.

[0542] Figure 14 is a simplified schematic cross-sectional view of an ophthalmic device 1400 according to several embodiments of the present invention.

[0543] In some embodiments, the curvature and / or inclination of the surface 1418 of the device 1400 varies along the cross-section of the device. For example, in some embodiments, the curvature of the front surface 1418 changes as it moves from the front edge 1466 toward the rear edge 1434, where the front edge 1466 and / or rear edge 1434 include one or more features described with respect to the front edge 666 and / or rear edge 634 in Figures 6A and 6B, respectively. For example, in a device 1400 having a retaining portion 1436 and / or retaining thickness 1424 with an inclination 1414, the curvature of the front surface 1418 then decreases toward the rear edge (e.g., from the thickest portion of the device). Here, in some embodiments, the inclination 1414 and / or retaining thickness 1424 have one or more features of the inclination 614 and / or thickness 624 in Figures 6A and / or 6B. In some embodiments, such a cross-section positions the retaining portion towards the side of the device proximal to the eyelid opening, for example, off-center with respect to the top view and / or footprint of the device when the device is in situ.

[0544] In some embodiments (for example, the front surface 1418 has a varying curvature), the rear surface 1416 has a constant curvature 1416. Alternatively, in some embodiments, the rear curvature 1416 also changes as it moves across one or more cross-sections of the device. For example, in some embodiments, thinning of the device away from the leading edge is due to a combination of decreasing curvature of the front surface and increasing curvature of the rear surface. In some embodiments (for example, the front surface 1418 has a constant curvature), thinning of the device away from the leading edge is due to an increase in curvature of the rear surface.

[0545] Referring now to Figure 15A, a simplified schematic top view of an ophthalmic device 1500 according to several embodiments of the present invention is shown. Referring also to Figure 15B, a simplified schematic diagram of an ophthalmic device 1500 according to several embodiments of the present invention is shown. Figure 15B shows an isometric view of the ophthalmic device 1500. Referring also to Figure 15C, a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention is shown. Finally, referring to Figure 15D, a simplified schematic cross-sectional view of an ophthalmic device 1500 according to several embodiments of the present invention is shown.

[0546] In some embodiments, the device 1500 is elongated. In some embodiments, the device 1500 is defined as having an elongated hemispherical shape, or also as having an elongated elliptical hemispherical shape. Here, in some embodiments, the elongated device 1500 includes one or more features described with respect to device 600 (Figure 6A). In exemplary embodiments, the device width 1520 is 1.1 to 10 times, or 1.1 to 5 times, or 1.2 to 3 times, or 1.2 to 2.5 times, or about 1.5 to 2 times, the device length 1522.

[0547] In some embodiments, the leading edge 1566 of the device 1500 is straight, and / or the trailing edge 1534 is straight. In some embodiments, the leading edge 1566 and the trailing edge 1534 are parallel (or within 1, 3, 5, or 10 degrees of parallel). In some embodiments, the leading edge 1566 and / or the trailing edge 1534 are straight, for example, when compared to the lateral edges 1580 and 1582. In other words, the leading edge 1566 and / or the trailing edge 1534 may include straight portions, while the lateral edges 1580 and 1582 are curved and therefore do not include straight portions.

[0548] In some embodiments, one or both of the lateral edges 1580 and 1582 are curved. A potential benefit is improved comfort for the user wearing the device. In some embodiments, one or both of the edges 1580 have a radius of curvature 1584. In an exemplary embodiment, the radius of curvature 1584 is half (or about half) the device footprint width 1520.

[0549] Figure 15C shows a cross-section of device 1500 taken transversely across the device, for example, along the longitudinal direction, for example, along line CC (in Figure 15A). In some embodiments, the device cross-section has a radius of curvature 1588 of the front surface 1518 extending from a first transverse edge 1580. In some embodiments, the cross-section has the same radius of curvature 1588 for the front surface 1518 extending from a second transverse edge 1582 to the central region and / or to the maximum thickness of the cross-section 1524. In some embodiments, the radius of curvature 1518 of the rear surface is 1 mm to 15 mm or 1 mm to 10 mm in one or more directions, and / or the ratio to that of the sclera is 0.1 to 2 or 0.5 to 1.

[0550] Figure 15D shows a cross-section of device 1500 taken, for example, along line DD (in Figure 15A) in the direction from the leading edge 1566 to the trailing edge 1534. In some embodiments, Figure 15D shows a cross-section of device 1500 extending along the central region 1590 of device 1500, for example, as indicated by arrow 1586. In some embodiments, the cross-section of Figure 15D includes one or more features of the cross-section of Figure 6B. In some embodiments, the radius of curvature 1590 of the front surface 1518 is the same as the maximum thickness 1590 of the cross-section. In some embodiments, the morphology of the ophthalmic device 1500 is dome-shaped or hemispherical.

[0551] In some embodiments, one or more of the radii of curvature 1584, 1588, and 1590 are relevant. In some embodiments, one or more of the radii of curvature 1584, 1588, and 1590 are the same as, approximately the same as, or within 5%, 10%, 20%, or 30% of each other with respect to one or more of them.

[0552] In some embodiments, the lateral sides of the device 1500 have the same curvature toward the lateral edges 1580, 1582 in the direction extending from the central region 1590 of the device 1500, and in some embodiments, the lateral edge of the front surface of the device has a quarter-hemispherical shape.

[0553] Figure 15C also shows a cross-section of device 1500 taken along line DD (in Figure 15A) (for example, as an alternative to Figure 15D), where the device has a flat central region of the front surface defined by the base 1502 of the front surface 1518 in Figure 15C.

[0554] In some embodiments, the device 1500 has a maximum thickness that extends along the lateral centerline CC of the footprint of the device 1500 (Figure 15A). In some embodiments, the maximum thickness extends along the central contour, for example, as indicated by arrow 1586.

[0555] In an exemplary embodiment, the width 1520 is 4.5 mm and the length 1522 is 10 mm. Herein, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is about 2.25 mm.

[0556] In exemplary embodiments, the width 1520 is approximately 5 mm, and the length 1522 is approximately 6.5 mm. Herein, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is approximately 2.25 mm.

[0557] In an exemplary embodiment, the width 1520 is approximately 4.5 mm, and the length 1522 is approximately 8.5 mm. Herein, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is approximately 2.25 mm.

[0558] In exemplary embodiments, the width 1520 is approximately 5.5 mm, and the length 1522 is approximately 10 mm. Herein, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is approximately 2.75 mm.

[0559] In an exemplary embodiment, the width 1520 is approximately 4 mm, and the length 1522 is approximately 6 mm. Herein, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is approximately 2 mm.

[0560] In an exemplary embodiment, the width 1520 is approximately 5.5 mm, and the length 1522 is approximately 8.5 mm. Herein, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is approximately 2.25 mm.

[0561] In exemplary embodiments, the width 1520 is approximately 4.5 mm, and the length 1522 is approximately 6.5 mm. Here, in some embodiments, the thickness 1524 and / or one or more of the radii of curvature 1584, 1588, and 1590 is approximately 2 mm. Here, in some embodiments, the weight of the device is 18 mg. In some embodiments, the minimum weight of the device is 8 mg.

[0562] Referring here to both Figures 15C and 15D, the rear surface 1516 is curved in at least one direction with respect to at least a portion of the rear surface 1516. For example, an alternative rear surface is shown, as indicated by the dashed lines in Figures 15C and 15D. In some embodiments, the rear surface of the device 1500 is concave in at least one direction.

[0563] A potential advantage of a concave posterior surface is increased adhesion of the device to the ocular surface on which it is mounted. In some embodiments, although not shown in Figures 15A–15D, the anterior portion (which may be multiple) has a larger radius of curvature RA than the posterior RP. For example, in some embodiments, RA is 1.2 to 10 times RP, or 1.2 to 5 times RP. While a description has been given with respect to the ocular surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood as distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other flat, etc.).

[0564] Here, we refer to a cross-section taken along line DD. In an exemplary embodiment, the height (and / or thickness) of the device is 1.32 mm at 0.5 mm from the leading edge 1566, the height (and / or thickness) of the device is 1.73 mm at a distance of 1 mm from the leading edge 1566, and the height (and / or thickness) of the device is 2 mm at a distance of 2 mm from the leading edge 1566. For example, in some embodiments, the radius of curvature 1588 and / or 1590 is 2 mm.

[0565] Referring now to Figures 16 to 20, simplified schematic top views of devices 1600, 1700, 1800, 1900, and 2000 according to several embodiments of the present invention are shown.

[0566] In some embodiments, the device 1600 is truncated on one or more sides, as shown, for example, in Figure 16. In some embodiments, the device 1600 has a curved edge 1666 and a low-curvature edge 1634 (for example, in some embodiments, the low-curvature edge 1634 is straight). In some embodiments, the region of the low-curvature edge 1634 has high curvature in the direction perpendicular to the plane of the footprint (and / or Figure 16). For example, in some embodiments, the edge 1634 accommodates a retaining portion having, for example, features (may be more) described with respect to retaining portions elsewhere in this specification (e.g., retaining portion 636 (Figure 6B)).

[0567] In some embodiments, the device 1700 has a top view shape that tapers in one or more directions, as shown, for example, in Figure 17. For example, the maximum width 1730 of the device tapers toward one or more edges 1766, 1734 of the device, for example, tapering more toward the first edge 1734 than toward the second edge 1766. In some embodiments, the maximum width 1730 is located closer to one edge than the other, for example, on the less tapered side of the device between the maximum width 1730 and edge 1766. In some embodiments, the second edge 1766 is the leading edge of the device, and the first edge 1734 is the trailing edge, and the leading and trailing edges include features (may be more) described elsewhere in this specification.

[0568] In some embodiments, as shown in Figure 18, for example, the ophthalmic device 1800 has a shape with a narrow portion 1848 and / or an outer recess.

[0569] In some embodiments, the shape of the device 1800 facilitates removal, for example, by pinching (e.g., manually and / or using a removal tool). Herein, for example, in some embodiments, a portion configured to fold in the central region of the device (in one or more dimensions) optionally has a thinner and / or smaller footprint range, facilitating folding after pinching force is applied to both or one of a larger area on either side of the smaller footprint portion. In some embodiments, the device 1800 includes two retaining portions, for example, one on each side of the folding region 1848.

[0570] In some embodiments, the shape of the device 1900, for example, the device footprint, is selected for anatomical fit, as shown in Figure 19, for example. In some embodiments, the device 1900 is shaped to position the device so that it contacts a portion of the patient's anatomical structure. In some embodiments, for example, an elongated device is curved and / or represents a curved shape. In some embodiments, the ophthalmic device 1900 includes a top view and / or footprint of the curved shape. In some embodiments, the central longitudinal axis 1930 of the curved shape is 1 mm to 40 mm long, or 5 mm to 20 mm long. In some embodiments, the radius of curvature of the device 1900 is selected so that the device follows the curvature of the eyelid and / or a portion of the fornix of the eyelid. Here, in some embodiments, the radius of curvature of 1928 is 20 mm to 100 mm, or 20 mm to 50 mm.

[0571] In some embodiments, the curve of the device 1900 is sized and / or shaped to conform to the curve of the eye, for example, the eyeball below the eyelid. In some embodiments, the retaining portion is housed adjacent to the edge 1966. Alternatively or additionally, in some embodiments, the retaining portion is housed adjacent to the edge 1934.

[0572] In some embodiments, as shown in Figure 20, for example, the device 2000 has one or more corners, for example, three corners for the device 2000, connected, for example, by edges. In some embodiments, the corners of the device 2000 facilitate removal of the device by pinching by reducing the device footprint area, for example, while the potential distance (e.g., related to range) for applying pinching force is the same (e.g., with a circular footprint device). In some embodiments, the retaining portion is housed in the central region of the footprint of the device 2000. In some embodiments, the retaining portion(s) are housed adjacent to one or more edges of a multi-edge device.

[0573] Referring now to Figures 21 to 24, simplified schematic cross-sectional views of devices 2100, 2200, 2300, and 2400 according to several embodiments of the present invention are shown.

[0574] In some embodiments, as shown in Figure 21, for example, the rear surface 2118 of the device 1300 includes one or more recesses 2138.

[0575] In some embodiments, as shown in Figure 22 for example, the device 2200 includes both the surface of the curved rear surface 2216 and one or more recesses 2238 on the rear surface 2218.

[0576] In some embodiments, as shown in Figure 23, for example, the device 2300 includes a recess 2338 located on the rear surface 2316. In some embodiments, the recess 2338 is located in the region of the retaining portion 2336. For example, the recess is adjacent to the front edge 2366 of the device, for example, within 1 mm to 5 mm from the front edge 2366. For example, it is located in the same portion (e.g., half) as the retaining portion 2336 of the device. Optionally, in some embodiments, the curvature of the front surface 2318 decreases in the direction from the maximum thickness 2330 of the device 2300 toward the rear edge 2334 of the device.

[0577] In some embodiments, as shown, for example in Figure 24, the device 2400 has a very concave rear surface 2416 compared to, for example, the device 2300 shown in Figure 23. In some embodiments, the curvature of the rear surface 2416 changes along the length of the surface, for example, from a first edge 2466 (which is the front edge in some embodiments) to a second edge 2434 (which is the rear edge in some embodiments). In some embodiments, the rear surface 2416 has a higher curvature in the region adjacent to the first edge 2466. In some embodiments, the height (or thickness of the retaining portion, as defined, for example, in the Overview section and / or with respect to Figures 6A and 6B) is measured between the dashed line shown in Figure 24 and the front surface 2418, where, in some embodiments, the dashed line represents a plane.

[0578] Referring now to Figure 25A, a simplified schematic cross-sectional view of a device 2500 placed on the eye surface according to several embodiments of the present invention is shown. Referring also to Figure 25B, a simplified schematic cross-sectional view of a device 2500 according to several embodiments of the present invention is shown. In some embodiments, Figures 25A and 25B show the same device and the same cross-sectional view of the same device 2500.

[0579] In some embodiments, the device 2500 includes an extended portion 2598 that is not covered by the eyelid 2546, for example, when the eye is open, as shown in Figure 25A. Here, in some embodiments, the body 2501 of the device 2500 is located below the eyelid 2546 (for example, when the eye is open, as shown in Figure 25A).

[0580] In some embodiments, the extended portion 2598 extends from the main body 2501 of the device 2500, which includes the retaining portion 2536.

[0581] In some embodiments, the extended portion 2598 is thin and / or has a thin edge. In some embodiments, the step formed between the leading edge 2566 of the device 2500 and the ocular surface (or a plane in contact with the device edge) is 1 to 500 microns, or 1 to 100 microns, or 10 to 50 microns. Thinness and / or small step potentially reduces the surface area that interacts with the eyelid when moving over the region of the extended portion, for example, during blinking and / or eye movements.

[0582] In some embodiments, the extended portion 2598 has a length 2596 of 0.5 mm to 6 mm. In some embodiments, the body 2501 has one or more features of devices, for example, described elsewhere in this specification. For example, one or more of the devices described elsewhere in this specification have an extended portion 2598 extending from the leading edge of the device.

[0583] In some embodiments, the body 2501 of the device is held in place below the eyelid. For example, in some embodiments, the body 2501 has a retaining portion 2536 which includes one or more features described and / or shown with respect to the retaining portion 636 (Figures 6A and 6B and / or elsewhere in this specification).

[0584] In some embodiments, the inclination and / or thickness of the retaining portion 2536 is measured relative to the edge 2594 of the retaining portion and to the extended portion 2598, and not, for example, to the leading edge 2566 of the device.

[0585] In some embodiments, the extended portion 2598 is used to add one or more materials and / or active pharmaceutical ingredients (APIs) to the tear meniscus (the valley between the eyelid margin and the eyeball, where tears accumulate and form a fluid reservoir).

[0586] Referring now to Figure 26, a simplified schematic cross-sectional view of device 2600 according to several embodiments of the present invention is shown.

[0587] In some embodiments, the device 2600 has extending portions 2698, 2699 that extend in two or more directions from the device body 2601. In some embodiments, a single extending portion surrounds the footprint of the device body 2601, where the device body 2601 includes one or more features shown and / or described with respect to the device body 2501 (Figures 25A and 25B). Here, one or both of the extending portions 2698, 2699 have one or more features shown and / or described with respect to the extending portion 2598 (Figures 25A and 25B).

[0588] Referring now to Figure 27A, a simplified schematic top view of an ophthalmic device 2700 according to several embodiments of the present invention is shown. Referring also to Figure 27B, a simplified schematic cross-sectional view of an ophthalmic device 2700 according to several embodiments of the present invention is shown. Figure 27B shows a cross-sectional view of the device 2700 of Figure 27A, taken, for example, along line EE of Figure 27A. In Figure 27A, the dotted lines are contour lines of the front surface 2716 of the device, and for the front surface, the solid lines indicate the same distance from the height defined by the plane of the device footprint shown in Figure 27A.

[0589] In some embodiments, the device 2700 includes two or more retaining portions 2736, 2737, where, in some embodiments, the retaining portions 2736, 2737 are connected by connecting portions 2706 having a thickness less than the thickness required by the retaining portions.

[0590] A potential advantage of having multiple retaining parts is that the device may be held under the eyelid if a retaining part slips away from under the eyelid. A potential advantage of having two or more raised parts of the device (e.g., provided by retaining parts) is that the surface protrudes to facilitate pinch removal, as described elsewhere in this specification. A potential advantage of having a connecting part 2706 instead of a single large retaining part is that the device volume of a long device can be reduced.

[0591] Returning to Figure 27A, this shows another embodiment having, in some embodiments, an edge 2766a (shown as a dashed line instead of edge 2766), where, in some embodiments, the edge 2766a has a notch extending toward, for example, a central region 2706, where the central region 2706 has a smaller extent and / or footprint than the central region 2706. In some embodiments, the device has a shape corresponding to an opposing edge 2734a (shown as a dashed line instead of edge 2734a).

[0592] In some embodiments, the cross-section of device 2700 in Figure 27A, which includes edge notches (which may be more), has the same cross-section as the cross-section described for device 2700 in Figure 27A, which does not include notches.

[0593] Referring now to Figure 27C, a simplified schematic cross-sectional view of device 2700 according to several embodiments of the present invention is shown.

[0594] Figure 27C shows embodiments of one or both of the devices shown in Figure 27A, where, in some embodiments, each retaining portion has concave curves 2718a, 2718b corresponding to the rear surface 2718a. Here, the concave surface includes one or more features described, for example, elsewhere in this specification with respect to a device having a single retaining portion. For example, it includes one or more features of the rear surface 616 (Figure 6B) and / or the rear surface 1516 (Figures 15C and 15D) and / or the rear surface 1316 (Figure 13B) and / or Figure 14. In some embodiments, the surface is concave in two or more directions, for example, a cross section taken along the line FF and / or line GG has a concave rear surface, for example, the cross section(s) have one or more features described and / or shown with respect to the cross section of Figure 13B and / or Figure 14.

[0595] 2.4. Exemplary Decomposition Referring here to Figure 28, the disassembly process of an ophthalmic device according to several embodiments of the present invention is shown. In addition, for disassembly according to specific elastomer matrices according to several embodiments of the present invention, please refer to Chapter 4 below.

[0596] In 2800, in several embodiments, a device placed in the eye (for example, under the eyelid of the eye) decomposes while maintaining the structural features (which may be multiple) of the retaining portion. The retaining portion acts to hold the device under the eyelid. During decomposition, in some embodiments, the device elutes one or more active pharmaceutical ingredients (APIs). In some embodiments, decomposition involves a loss of mass.

[0597] In 2802, in some embodiments, for example, the retaining part is disassembled after the disassembly and / or collapse of other parts (which may be more than one) of the device.

[0598] In 2804, in some embodiments, when the retaining portion is disassembled, the device exits the eye, for example, from under the eyelid.

[0599] Figure 29 is a simplified schematic cross-sectional view of device 2900 according to several embodiments of the present invention.

[0600] In some embodiments, contours 2910, 2912, 2916, and 2926 indicate the front surface of device 2900 over time, for example, as it disintegrates while device 2900 remains in view. In some embodiments, the inclination and / or thickness of the retaining portion is maintained, for example, through the transition of the device front surface from 2910 to 2912 and 2916, and only thereafter, in some embodiments, the thickness (e.g., as shown) and / or inclination of the retaining portion decreases.

[0601] In some embodiments, the device 2900 comprises different parts having different decomposition rates. Herein, in some embodiments, part 2971 comprises a material that decomposes more slowly (or does not decompose in the eye) than the other parts of the device. In some embodiments, the slow-decomposing part of the device (e.g., part 2971) is sized and / or shaped and / or positioned relative to the other parts of the device, for example, to maintain a retaining portion during the decomposition of the other parts(s) of the device.

[0602] Referring now to Figures 30A and 30B, simplified schematic cross-sectional views of device 3000 according to several embodiments of the present invention are shown.

[0603] In some embodiments, the device 3000 includes different parts 3032, 3030 having different disintegration times. In some embodiments, the rear part 3030 adjacent to the rear surface 3016 of the device 3000 disintegrates more quickly than the front part 3032 adjacent to the front surface 3018 of the device 3000. This is shown, for example, in the transition of the device cross-section shown in the transition from A to B in Figure 30. In some embodiments, the disintegration of the front surface of the device 3000, for example, in some embodiments, combined with the device's resistance to collapse on the ocular surface, maintains the inclination and / or height of the device on the ocular surface, and maintains, for example, the properties of the retaining portion(s).

[0604] 2.5. Exemplary Ophthalmic Devices Referring now to Figure 31A, a simplified schematic cross-sectional view of an ophthalmic device 3100 on the ocular surface 3104 according to several embodiments of the present invention is shown. Referring also to Figure 31B, a simplified schematic view of an ophthalmic device 3100 according to several embodiments of the present invention is shown. Referring also to Figure 31C, a simplified schematic view of an ophthalmic device 3100 according to several embodiments of the present invention is shown.

[0605] In some embodiments, the device 3100 includes a rear surface 3116 and a front surface 3118.

[0606] In some embodiments, the device 3100 includes a plurality of layers 3110, 3112, where, in some embodiments, the layers generally conform to the surface of the device.

[0607] In some embodiments, the first layer 3110 is adjacent to and / or in contact with the ocular surface 3104 and / or forms at least a portion of the posterior surface 3116. In some embodiments, the first layer 3110 includes a mucosal adhesive material. Although a description has been given with respect to the ocular surface, in some embodiments, as described above, the posterior and anterior surfaces should be understood to be distinct from each other, regardless of whether they are on the inside or outside of the eye. In some embodiments, the posterior and anterior surfaces have different shapes (e.g., one is convex and the other concave, one is curved and the other is flat, etc.).

[0608] In some embodiments, the second layer 3112 contacts the inner surface of the eyelid at least periodically and / or forms at least a portion of the front surface 3114. In some embodiments, the second layer has a smooth outer surface and / or contains a lubricating material. In some embodiments, one or both of the first layer 3110 and the second layer 3112 contain and / or elute a therapeutic material(s).

[0609] Figure 31B shows the determination of the range of device 3100, where the range is the average of one or more dimensions and / or two or more dimensions of the bounding box 3164, which is the smallest rectangular parallelepiped shape in which device 3100 is contained.

[0610] In some embodiments, the device 3100 includes one or more additional layers (as described elsewhere in this specification, for example).

[0611] In some embodiments, the ophthalmic device has a thickness of less than 100 microns (e.g., the maximum and / or average thickness in the central 50% of the device). In some embodiments, the ophthalmic device has a thickness of approximately 1 micron to approximately 200 microns. In some embodiments, the device has a thickness of approximately 1 micron, or approximately 2 microns, or approximately 3 microns, or approximately 4 microns, or approximately 5 microns, or approximately 6 microns, or approximately 7 microns, or approximately 8 microns, or approximately 9 microns, or approximately 10 microns, or approximately 15 microns, or approximately 20 microns, or approximately 25 microns, or approximately 30 microns, or approximately 35 microns, or approximately 40 microns, or approximately 45 microns, or approximately 50 microns, or approximately 55 microns, or approximately 60 microns, or approximately 70 microns, or approximately 80 microns, or approximately 90 microns, or approximately 100 microns, or approximately 110 microns, or approximately 120 microns, or approximately 130 microns, or approximately 140 microns, or approximately 150 microns, or approximately 160 microns, or approximately 170 microns, or approximately 180 microns, or approximately 190 microns, or approximately 200 microns. In some embodiments, the device has a thickness of approximately 10 microns to approximately 100 microns.

[0612] In some embodiments, the thickness of the first (e.g., mucosal adhesive) layer 3166 and / or the thickness of the second (e.g., lubricating) layer 3164 and / or the thickness of an optional additional intermediate layer (one or more) (e.g., as described elsewhere in this specification) is less than 100 microns (e.g., the maximum thickness and / or average thickness in the central 50% of the device). In further embodiments, one or more layers have a thickness of about 1 micron to about 200 microns. In some embodiments, the lubricating layer and / or the mucosal adhesive layer and / or the intermediate layer have a thickness of approximately 1 micron, 2 microns, 3 microns, 4 microns, 5 microns, 6 microns, 7 microns, 8 microns, 9 microns, 10 microns, 15 microns, 20 microns, 25 microns, 30 microns, 35 microns, 40 microns, 45 microns, 50 microns, 55 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100 microns, 110 microns, 120 microns, 130 microns, 140 microns, 150 microns, 160 microns, 170 microns, 180 microns, 190 microns, and 200 microns. In some embodiments, one or more layers have a thickness of approximately 1 micron to approximately 10 microns.

[0613] In some embodiments, one or more layers have approximately the same thickness as one or more other layers. In some embodiments, one or more layers have a different thickness from one or more other layers. In some embodiments, one or more layers have a non-uniform thickness. For example, they become thinner outward from the central region of the device toward the edge region(s) of the device. For example, the layers have cavities and / or holes and / or protrusions(s).

[0614] Referring now to Figures 32 to 37, simplified schematic cross-sectional views of parts of ophthalmic devices according to several embodiments of the present invention are shown. In Figures 32 to 37, shaded areas indicate the presence of active pharmaceutical ingredients (APIs) (there may be multiple).

[0615] Referring here to Figures 32 and 35, in some embodiments, the second layers 3212, 3512 (for example, including one or more features described with respect to the second layer 3112 (Figures 31A to 31C)) contain a pharmaceutically active ingredient (which may be more than one) (API). For example, it may be dispersed within the second layer 3112 and / or located within one or more regions 3514 of the second layer 3512.

[0616] Referring now to Figures 33 and 36, in some embodiments, the first layers 3310, 3610 (for example, including one or more features described with respect to the first layer 3110 (Figures 31A to 31C)) contain a pharmaceutically active ingredient (API) (which may be multiple). For example, it may be dispersed within the first layer 3110 and / or located within one or more regions 3614 of the second layer 3610.

[0617] Referring here to Figures 34 and 37, in some embodiments, both the first layers 3410, 3710 (for example, including one or more features described with respect to the first layer 3110 (Figures 31A to 31C)) and the second layers 3412, 3712 (for example, including one or more features described with respect to the second layer 3112 (Figures 31A to 31C)) contain a pharmaceutically active ingredient (or more) (API). For example, it is dispersed in the first layer 3410 and / or the second layer 3412, and / or located in one or more regions 3714 of the second layer 3712 and / or the first layer 3710. Here, in some embodiments (not shown), one layer contains a portion having the therapeutic material, and the other layer has the therapeutic material dispersed therein. In some embodiments, the separate region(s) containing the therapeutic material contains a different therapeutic material from the layer in which the therapeutic material is dispersed. In some embodiments, individual regions (or multiple regions) are encapsulated by other materials, which, for example in some embodiments, are eroded before the therapeutic material begins to dissolve into the eye.

[0618] Referring here to Figures 38 to 44, simplified schematic cross-sectional views of devices 3800, 3900, 4000, 4100, 4200, 4300, and 4400 according to several embodiments of the present invention are shown.

[0619] In some embodiments, the device has a rear surface that is flat or has a high radius of curvature (e.g., rear surface 3816 of device 3800 (Figure 38), e.g., rear surface 3916 of device 3900 (Figure 39), e.g., rear surface 3406 of device 4000 (Figure 40), e.g., rear surface 4116 of device 4100 (Figure 41)). Here, in some embodiments, the high radius of curvature is greater than 5 mm, or greater than 10 mm, or greater than 9.6 mm, or 8 mm to 12 mm, or 9 mm to 11 mm.

[0620] In some embodiments, the device has a concave rear surface (e.g., rear surface 4216 of device 4200, e.g., rear surface 4316 of device 4300, e.g., rear surface 4416 of device 4400). Herein, in some embodiments, the concave rear surfaces 4216, 4316, 4416 include one or more features shown and / or described elsewhere in this specification with respect to concave and / or curved rear surfaces (may be more than one).

[0621] In some embodiments, the device and / or the cross-section of the device includes a single cavity, for example, in some embodiments, elements 3830, 3930, and 4030 in Figures 38 to 40 are cavities, where, in some embodiments, the cavities 3830, 3930, and 4030 are located on the rear surfaces 3816, 3916, and 4016 of the device.

[0622] In some embodiments, the device and / or the cross-section of the device include a single portion having a different material, for example, a mucosal adhesive material, for example, in some embodiments, elements 3830, 3930, and 4030 in Figures 38 to 40 are cavities. Here, in some embodiments, the mucosal adhesive portions 3830, 3930, and 4030 are located on the rear surfaces 3816, 3916, and 4016 of the device, respectively.

[0623] Refer to Figures 41 and 42 here. In some embodiments, the device and / or the cross-section of the device has a single portion having a different material 4130, 4230, for example, a mucosal adhesive material, and a single cavity 4132, 4232. Here, in some embodiments, the cavities 4130, 4230 and the different material portion 4132, 4232 are located on the rear surfaces 4116, 4216 of the device 4100, 4200, respectively.

[0624] In some embodiments, the device and / or the cross-section of the device have two parts of different materials (which may be more than one), and parts 4130, 4132 of device 4100 and / or parts 4230, 4232 of device 4200 have the same material or different materials.

[0625] In some embodiments, the cross-sections of devices 4100, 4200 and / or devices each have two cavities 4130, 4132 and 4230, 4232.

[0626] Referring here to Figures 43 and 44, in some embodiments, the devices 4300, 4400 have both two or more recesses 4330, 4432 and two or more different material portions 4332, 4432, all of which, in some embodiments, are located on the rear surfaces 4316, 4416 of the devices 4300, 4400, respectively. In some embodiments, one or more of the cavities and / or one or more of the different material portions are located within the body of the device and / or on different device surfaces, for example, on the front surfaces 4318, 4418 of the device.

[0627] Referring now to Figure 43, in some embodiments, the cavity(s) 4330 is located on the rear surface 4316 and / or the device body 4300 more centrally than the portion(s) 4332 of a different material (e.g., mucosal adhesive).

[0628] Referring now to Figure 44, in some embodiments, a portion(s) 4432 made of a different material (e.g., mucosal adhesive) is positioned on the rear surface 4416 and / or on the rear surface 4416 that is more central to the device body 4400 than the cavity(s) 4430.

[0629] Referring now to Figures 45 to 50, simplified schematic cross-sectional views of two-layer devices 4500, 4600, 4700, 4800, 4900, and 5000 according to several embodiments of the present invention are shown.

[0630] In some embodiments, devices 4500, 4600, 4700, 4800, 4900, and 5000 each have rear surfaces 4516, 4616, 4716, 4816, 4916, and 5016, respectively, and front surfaces 4518, 4618, 4718, 4818, 4918, and 5018, respectively.

[0631] In some embodiments, devices 4500, 4600, 4700, 4800, 4900, and 5000 include a first layer 4510, 4610, 4710, 4810, 4910, and 5010, and a second layer 4512, 4612, 4712, 4812, 4912, and 5012. Herein, in some embodiments, the first layer has one or more features described and / or shown with respect to the first layer 3110 (Figures 31A to 31C) and / or one or more of the first layers 3210, 3210, 3310, 3410, 3510, 3610, and 3710 of Figures 31A to 37, respectively. Herein, in some embodiments, the second layer has one or more features described and / or shown with respect to the second layer 3112 (Figures 31A to 31C) and / or one or more of the second layers 3212, 3212, 3312, 3412, 3512, 3612, and 3712 of Figures 31A to 37, respectively.

[0632] In some embodiments, the device has a rear surface that is flat or has low curvature (as defined elsewhere herein, for example) in the dry and / or hydrated state (e.g., rear surface 4516 in Figure 45, rear surface 4616 in Figure 46, rear surface 4716 in Figure 47, rear surface 4916 in Figure 49).

[0633] Referring here to Figures 45 and 47, in some embodiments, the second layer 4512, 4712 (e.g., including a lubricating material) extends around the body of the device, for example, covering the edge(s) 4568 of the device and / or forming part(s) of the proximal surface 4516, 4716 of the device (e.g., the edge(s)).

[0634] Referring here to Figures 45 to 47, in some embodiments, the first layer and / or the second layer have substantially uniform thickness across the entire area of ​​the device and / or along one or more cross-sections of the device (e.g., layers 4510, 4512, 4610, 4612 in Figure 45, and layer 4712 in Figure 47).

[0635] Refer to Figures 47 to 50 here. In some embodiments, one or more layers have one or more of the following thicknesses: the maximum thickness at the center and / or central region of the device, and the thickness that decreases as it moves from the central region toward the edge(s) of the device (e.g., layer 4710 in Figure 47, layers 4810 and 4812 in Figure 48, layers 4910 and 4912 in Figure 49, and layer 5012 in Figure 50).

[0636] Figure 45 shows a device 4500 having a flat and / or low curvature rear surface 4516 and a front surface 4518, where a second layer 4512 extends around the edge of the device 4500 and forms part of the front surface 4518. Here, the layers are individually of substantially uniform thickness.

[0637] Figure 46 shows a device having a flat and / or low curvature rear surface 4616 and a front surface 4618, where the layers are individually of substantially uniform thickness.

[0638] Figure 47 shows a device 4700 having a flat and / or low curvature rear surface 4716 and a convex front surface 4718, with a second layer 4712 extending around the edge of the device 4700 to form part of the front surface 4718. In some embodiments, the second layer 4712 has a substantially uniform thickness. In some embodiments, the first layer 4710 has its maximum thickness at the center and / or central region of the device, and its thickness decreases as it moves from the central region toward the edge(s) of the device 4700.

[0639] Figure 48 shows a device 4800 having both a concave rear surface 4816 and a convex front surface 4818. Here, in some embodiments, both the first layer 4810 and the second layer 4812 have their maximum thickness at the center and / or central region of the device, and their thickness decreases as they move from the central region toward the edge(s) of the device 4800.

[0640] Figure 49 shows a device 4900 in which the rear surface 4916 is flat or has low curvature and the front surface 4918 is convex. Here, in some embodiments, both the first layer 4910 and the second layer 4912 have the greatest thickness at the center and / or central region of the device, and the thickness decreases as it moves from the central region toward the edge(s) of the device 4900.

[0641] Figure 50 shows a device 5000 having a boundary plane with a convex rear surface in some embodiments. In some embodiments, the rear surface has a cross section having one or more protrusions 5034 and / or one or more cavities 5030, for example, two protrusions 5034 defining a cavity 5030 between them. In some embodiments, the thickness of one or both layers is irregular. In some embodiments, the rear surface 5016 has an irregular shape, a convex shape, or a shape having multiple recesses.

[0642] Referring here to Figures 51 to 58, simplified schematic cross-sectional views of multilayer devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, and 5800 according to several embodiments of the present invention are shown.

[0643] In some embodiments, devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, and 5800 each have rear surfaces 5116, 5216, 5316, 5416, 5516, 5616, 5716, and 5816, respectively, and front surfaces 5118, 5218, 5318, 5418, 5518, 5618, 5718, and 5818, respectively.

[0644] In some embodiments, devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, and 5800 include a first (e.g., mucosal-adherent) layer 5110, 5210, 5310, 5410, 5510, 5610, 5710, and 5810, and a second (e.g., lubricating) layer 5112, 5212, 5312, 5412, 5512, 5612, 5712, and 5812. Herein, in some embodiments, the first layer has one or more features described and / or shown with respect to the first layer 3110 (Figures 31A to 31C) and / or one or more of the first layers 3210, 3210, 3310, 3410, 3510, 3610, and 3710 of Figures 31A to 37, respectively. Herein, in some embodiments, the second layer has one or more features described and / or shown with respect to the second layer 3112 (Figures 31A to 31C) and / or one or more of the second layers 3212, 3212, 3312, 3412, 3512, 3612, and 3712 of Figures 31A to 37, respectively.

[0645] In some embodiments, devices 5100, 5200, 5300, 5400, 5500, 5600, 5700, and 5800 include intermediate layers 5136, 5236, 5336, 5436, 5536, 5636, 5736, and 5836, respectively. In some embodiments, the intermediate layer is positioned between the first and second layers. Here, in some embodiments, the intermediate layer is covered by other layers, for example, as shown in Figures 51-55 and Figures 57 and 58. In some embodiments, the intermediate layer contains a therapeutic material (for example, dispersed within and / or in part(s) of the layer).

[0646] Figure 51 shows a device 5100 having a flat and / or low curvature rear and front surface (5116 and 5118, respectively). Here, in some embodiments, the second surface extends to cover the edge of the device 5100, for example, surrounding the side surface of the intermediate surface 5136. In some embodiments, one or more (e.g., all) of the first layer 5110, the second layer 5112, and the third layer 5136 have substantially uniform thickness. In some embodiments, the thickness of the intermediate layer 5136 is greater than one or more of the other layers, for example, 1.5 to 10 times thicker.

[0647] Figure 52 shows a device 5200 in which the rear surface 5216 is convex.

[0648] In some embodiments, the thicknesses of the first layer 5210 and the second layer 5212 are approximately the same, and in some embodiments, they are substantially uniform. In some embodiments, the intermediate layer 5236 has a thicker central region and its thickness decreases towards the edges of the device 5200. In some embodiments, the average and / or maximum thickness of the intermediate layer 5236 is 1.5 to 10 times thicker than the thickness of one or both of the first layer 5210 and the second layer 5212.

[0649] In some embodiments, the convex rear surface reduces the attractive force between the eyeball and the device, potentially increasing the user's comfort with the device and / or facilitating removal of the device. In some embodiments, the device includes the shapes of the front 5216 and rear 5218 of the device 5200 in Figure 52, but has a different layer structure and / or internal composition than those described in the previous paragraph.

[0650] Figure 53 shows a device 5300 in which the first layer 5310, the intermediate layer 5336, and the second layer 5312 each have a thicker central region, and the thickness of the layers decreases towards the edges of the device 5300. In some embodiments, the second layer 5312 is positioned around the device 5300 to form part of the rear surface 5316. In some embodiments, the rear surface 5316 has a higher radius of curvature than the front surface 5318 (for example, the radius of curvature includes one or more features described elsewhere in this specification, e.g., in the Summary section).

[0651] Figure 54 shows a device 5400 in which the first layer 5410, the intermediate layer 5436, and the second layer 5412 each have a thicker central region, and the thickness of the layers decreases towards the edges of the device 5400. In some embodiments, the thickness of the layers is substantially the same in the central region of the device and / or across one or more cross-sections of the device.

[0652] In some embodiments, the device 5500 of Figure 55 has the same characteristics as the device 5100 of Figure 51, except that the intermediate layer 5536 is, in some embodiments, substantially the same thickness as one or both of the first layer 5510 and the second layer 5512.

[0653] Figure 56 shows a device 5600 having a constant thickness along a cross-section in which each layer 5610, 5612, and 5636 is shown. In some embodiments, the intermediate layer 5636 contains a therapeutic material. In some embodiments, the intermediate layer 5636 is thicker than one or both of the other layers 5612, 5610 (e.g., 1.5 to 10 times the thickness of the mucosal adhesion layer 5610 and / or lubricating layer 5612). In some embodiments, the intermediate layer 5636 contains multiple layers.

[0654] Figure 57 shows a device 5700 having a convex front surface 5718 and a flat or low curvature rear surface 5716. In some embodiments, the mucosal adhesion layer 5716 has a uniform thickness across one or more cross-sections of the device. In some embodiments, the lubricating layer 5712 has a uniform thickness along a path around the circumference of the intermediate layer 5736. In some embodiments, the intermediate layer 5736 is thicker in the central region of one or more cross-sections of the device 5700, and in some embodiments, its thickness decreases towards the edges (or more) of the device. In some embodiments, the lubricating layer 5712 does not form part of the rear surface 5716.

[0655] Figure 58 shows a device 5800 having a convex front surface 5818 and a concave rear surface 5816. In some embodiments, the mucosal adhesion layer 5816 has a uniform thickness across one or more cross-sections of the device. In some embodiments, the lubricating layer 5812 has a uniform thickness along a path around the circumference of the intermediate layer 5836. In some embodiments, the intermediate layer 5836 is thicker in the central region of one or more cross-sections of the device 5800, and in some embodiments, its thickness decreases towards the edges (or more) of the device. In some embodiments, the lubricating layer 5812 does not form part of the rear surface 5816.

[0656] Referring now to Figure 59A, a simplified schematic cross-sectional view of an ophthalmic device 5900 according to several embodiments of the present invention is shown.

[0657] In some embodiments, the device 5900 includes both a retaining portion 5936 (for example, including one or more features described with respect to the retaining portion elsewhere in this specification) and a thin edge portion 5971.

[0658] In some embodiments, the edge of the device (e.g., the circumferential edge) has an average thickness 5969 of about 15 microns, or about 20 microns, or about 30 microns, or about 50 microns, at a distance 5967 defined as the shortest distance between the rear surface 5916 and the front surface 5918 of the device. In some embodiments, the ophthalmic device has a thin edge of about 15 microns, or about 20 microns. In some embodiments, the ophthalmic device has an edge thickness of about 5 to 200 microns, or 5 to 200 microns.

[0659] In some embodiments, the distance 5967 is 0.1 mm to 1 mm, or 0.1 mm to 0.5 mm, of the device. In some embodiments, the distance 5967 is approximately 0.1 mm, or approximately 0.5 mm.

[0660] In some embodiments, the thin edge 5971 extends over a region of the device 5900, for example, a portion of the circumferential edge of the device, for example, 20% to 99% or 80% to 90% of the circumference of the device, for example, a side of the device, for example, only the trailing edge or only the leading edge, for example, two or more sides of the device, for example, the leading edge and the trailing edge, for example, two opposing sides.

[0661] Figure 59A shows device 5900 in a relaxed state.

[0662] Figure 59B is a simplified schematic cross-sectional view of an ophthalmic device 5900 according to several embodiments of the present invention.

[0663] Figure 59B shows the device of Figure 59A when it is in place on the ocular surface (for example, below the eyelid). In some embodiments, when the device 5900 is on the ocular surface, the thin edge 5971 is flexible and conforms to the ocular surface 5904.

[0664] Referring now to Figure 60, a simplified schematic cross-sectional view of an ophthalmic device according to several embodiments of the present invention is shown.

[0665] Figure 60 shows the device of Figure 59A in position on the ocular surface when the thin edge penetrates the ocular surface, as described, for example, in the Overview section of this specification.

[0666] Referring now to Figure 61, a simplified schematic cross-sectional view of an ophthalmic device 6100 according to several embodiments of the present invention is shown.

[0667] In some embodiments, the device 6100 has a convex rear surface 6116. In some embodiments, the device 6100 has a retaining portion 6136 that includes one or more features of retaining portions described elsewhere in this specification (e.g., retaining portion 636 in Figure 6B), where, in some embodiments, the height is measured from the ocular surface 6104 as indicated by the vertical arrow in Figure 61.

[0668] Alternatively, in some embodiments, the height is measured from the plane on which the device is mounted. Alternatively, in some embodiments, the height is measured from a plane 6199 connecting the edges (or most of the circumferential edges) of the device, or from a plane drawing the cross-section of the device's largest area, the plane located between the front 6118 and the rear 6116.

[0669] Referring now to Figure 62A, a simplified schematic cross-sectional view of a portion of the ocular surface according to several embodiments of the present invention is shown.

[0670] Referring now to Figure 62B, a simplified schematic cross-sectional view of an ophthalmic device 6200 on the eye surface according to several embodiments of the present invention is shown.

[0671] Referring now to Figure 62C, a simplified schematic cross-sectional view of an ophthalmic device 6200 on the eye surface according to several embodiments of the present invention is shown.

[0672] In some embodiments, there is an ophthalmic epithelial layer 6258 on top of the substantial 6260, an aqueous tear film layer 6256 on top of that, and a lipid layer 6254 on top of that.

[0673] Figure 62A shows, for example, a cross-section of the anatomical structure of the eye before the application of device 6200 to the eye.

[0674] Figure 62B shows the anatomical structure of the device 6200 and the eye immediately after and / or shortly after application of the device 6200.

[0675] Figure 62C shows the anatomical structure of the device 6200 and the eye at any time after application of the device, where, in some embodiments, the time period is approximately 1 minute to 1 hour after application.

[0676] In some embodiments, the device body 6200 includes a rear surface 6216 and a front surface 6218, as shown in Figure 62B, for example. In some embodiments, the body 6200 tapers in thickness towards the edges of the body.

[0677] In some embodiments, the device 6200 includes cavities 6230, 6232, which, in some embodiments, are located on the rear surface 6216.

[0678] In some embodiments, after application of the device, tear fluid fills the cavities 6232 and 6234, and the epithelium 6258 is the same as before application of the device. In some embodiments, tear fluid, for example, aqueous and / or lipids, coats the device (not shown).

[0679] In some embodiments, for example as shown in Figure 62C, after an arbitrary period of time, the ocular tissue conforms to the shape of the device 6200. For example, the epithelial tissue 6258 forms a localized projection 6260 toward the cavity 6230 / 6232, for example, under suction at the cavity entrance. Potentially, the epithelial projection(s) 6260 fix the device 6200 in place, reducing, for example, the possibility of device migration and / or ejection.

[0680] Referring now to Figures 63A-C, these are simplified schematic cross-sectional views of some of the devices 6300 on the eye surface 6358 according to several embodiments of the present invention.

[0681] Figure 63A shows the anatomical structure of the eye 6358 with the device 6300 immediately after and / or shortly after application of the device 6300.

[0682] Figure 63B shows the device 6300 and the anatomical structure of the eye 6358 during a first period after the application of the device. Here, in some embodiments, the first period is 1 minute to 1 hour.

[0683] Figure 63C shows the device 6300 and the anatomical structure of the eye 6358 in a second period, for example, 1 minute to 1 hour after the cross-section shown in Figure 63B.

[0684] In some embodiments, for example, as shown in Figure 63A, the device body 6300 includes a cavity 6330 and a rear surface 6316 including a projection 6334.

[0685] In some embodiments, after application of the device, the tear film fills the cavity 6330, and the epithelium 6358 is the same as before application of the device.

[0686] In some embodiments, as shown in Figure 63B, for example, after a first period, the ocular tissue conforms to the shape of the device 6300. For example, the epithelial tissue 6358 locally protrudes to form a projection 6360 toward the cavity 6330 and / or recedes to form a recessed portion 6362 in the flexible epithelial tissue in the area adjacent to the projection 6334. Here, in some embodiments, the receded material potentially secures the device 6300 and potentially reduces the possibility of movement and / or ejection of the device 6300.

[0687] In some embodiments, biodegradation and / or biological and / or mechanical erosion of the device 6300 occurs, for example, as shown in Figure 63C. Here, in some embodiments, the size of the projection 6334 is reduced (for example, in one or more dimensions), and / or the corners (may be more than one) of the projection 6334 are rounded. Here, in some embodiments, the corners of the cavity 6330 are rounded. In some embodiments (not shown), the cavity is wider in one or more dimensions, and / or its depth is varied, for example, becoming shallower or deeper.

[0688] In some embodiments, the rear surface 6316 of C in Figure 63 shows an exemplary proximal surface shape, for example, including projections (which may be multiple) 6334 and / or cavities (which may be multiple) 6330.

[0689] Referring now to Figures 64 to 66, simplified schematic cross-sectional views of multilayer devices 6400, 6500, and 6600 according to several embodiments of the present invention are shown.

[0690] Figures 64 to 66 show the elution of the active pharmaceutical ingredient (API) as indicated by the arrows.

[0691] In some embodiments, for example as shown in Figure 64, the intermediate layer 6436 contains a therapeutic material and is not covered by other layers (which may be more) (6412, 6410) at the edges of the device 6400. In some embodiments, the layer elutes pharmaceutically active ingredients (which may be more) (APIs) through the edges (optionally without going through surfaces 6418, 6419), for example as indicated by the arrows.

[0692] In some embodiments, for example as shown in Figure 65, the intermediate layer 6536 contains a therapeutic material and is not completely covered by the second lubricating layer 6512, and the pharmaceutically active ingredient(s) (API) elutes through the second layer (for example, through channels(s) and / or pores 6530 of layer 6512, as indicated by the arrows in Figure 65). In some embodiments, instead of having channels(s) and / or pores, the second layer 6512 contains a material that allows diffusion of the pharmaceutically active ingredient(s) (API) through the material. In some embodiments, the elution of the pharmaceutically active ingredient(s) (API) does not occur through the surface 6518 or 6516 of layer 6512 or 6510.

[0693] In some embodiments, for example as shown in Figure 66, the intermediate layer 6636 contains a therapeutic material and is not completely covered by the first mucosal adhesive layer 6610 (for example, through the edges and / or through the second lubricating surface 6612 of the device), and the pharmaceutically active ingredient(s) (API) elutes through the first layer (for example, through channels(s) and / or pores 6630 of layer 6610, as indicated by the arrows in Figure 66). In some embodiments, instead of having channels(s) and / or pores, the first layer 6610 contains a material that allows diffusion of the pharmaceutically active ingredient(s) (API) through the material.

[0694] Referring now to Figures 67A to F, simplified schematic cross-sectional views of parts of the device as the residence time of the device elapses, according to several embodiments of the present invention.

[0695] Referring now to Figure 68, a flowchart of the device's decay progression according to several embodiments of the present invention is shown.

[0696] Figure 67A shows the device layer structure before the device is placed on the ocular surface. The device includes a first mucosal adhesion layer 6710, an intermediate layer 6736, and a second lubricating layer 6712.

[0697] In the 6800, in some embodiments, the device 6700 is positioned on the ocular surface 6758.

[0698] In 6802, in some embodiments, the lubricating layer 6712 is decomposed and / or dissolved and / or eroded, causing, for example, the device 6700 to transition from the configuration shown in Figure 67B to the configuration shown in Figure 67C.

[0699] In 6804, in some embodiments, the intermediate layer 6736 is partially decomposed and / or dissolved and / or eroded, for example, to transition the device 6700 from the configuration shown in Figure 67C to the configuration shown in Figure 67D, and then to the configuration shown in Figure 67E.

[0700] In 6806, in some embodiments, the mucosal adhesive layer 6710 is dissolved and / or decomposed and / or eroded, for example, to transition the eye from the configuration shown in Figure 67E to the configuration shown in Figure 67F.

[0701] Referring now to Figures 69A to C, simplified schematic cross-sectional views of the device 6900 as the residence time of the device elapses, according to several embodiments of the present invention.

[0702] In some embodiments, Figures 69A to C show a portion of the device (for example, a central portion where the edges are not shown).

[0703] In Figures 69A to C, similar shading in several embodiments indicates areas with the same material properties (e.g., lubricity, mucosal adhesion, therapeutic material content).

[0704] In some embodiments, the device 6900 includes a rear surface 6916 ...

Claims

1. An ophthalmic device configured to be located between the ocular surface of the eyeball and the eyelid, The ophthalmic device comprises a body made from an elastomer matrix containing water, one or more types of PVOH, and one or more types of organic plasticizers. The aforementioned main body, i. The posterior surface adjacent to the ocular surface when the ophthalmic device is attached, ii. The front surface adjacent to the eyelid that covers the ocular surface when the ophthalmic device is attached, iii. A retaining portion defined between a part of the front surface and a part of the rear surface, Characterized by, An ophthalmic device in which the ratio of the total mass of one or more organic plasticizers and one or more PVOHs is at least 2:

1.

2. The ophthalmic device according to claim 1, wherein the holding portion is configured to move together with the eyelid when the eyelid moves relative to the eyeball.

3. The ophthalmic device according to claim 1 or 2, wherein the angle of inclination of the front surface extending from the rear surface is greater than 45 degrees.

4. The ophthalmic device according to any one of claims 1 to 3, wherein the relationship between the width and length of the ophthalmic device is approximately 1:1 to approximately 1:

3.

5. The ophthalmic device according to any one of claims 1 to 4, wherein the main body swells isotropically when immersed in simulated tear solution for 15 minutes or less.

6. An ophthalmic device according to any one of claims 1 to 5, further comprising at least one ophthalmologically acceptable pharmaceutically active ingredient (API).

7. The ophthalmic device according to any one of claims 1 to 6, wherein the water constitutes 5 wt% to 50 wt% of the elastomer matrix.

8. The ophthalmic device according to any one of claims 1 to 7, wherein the ophthalmic device is configured to increase in weight by 50% or less when immersed in simulated tear solution for 15 minutes or less.

9. An ophthalmic device according to any one of claims 1 to 8, which can be obtained without freezing from a liquid solution containing water, an ophthalmologically acceptable pharmaceutically active ingredient (API), the PVOH, and a water-soluble organic liquid.

10. An ophthalmic device according to any one of claims 1 to 9, comprising two or more types of PVOH.

11. The ophthalmic device according to claim 10, wherein the ratio between the two or more types of PVOH is such that the ophthalmic device disintegrates within 24 hours in simulated tears (STF).

12. The ophthalmic device according to claim 10, wherein the ratio between the two or more types of PVOH is such that the ophthalmic device maintains its original shape in artificial tears (STF) for the first 10 minutes.

13. An ophthalmic device according to any one of claims 1 to 12, which is visible to the naked eye against the conjunctiva of the eye as a background.

14. The ophthalmic device according to any one of claims 1 to 13, wherein the ophthalmic device is elongated and symmetrical, and all orientations of the device are equivalent as long as the elongated side of the device is in a given direction.

15. The ophthalmic device according to any one of claims 1 to 14, wherein the holding portion is defined by the height between the rear surface and the front surface, and the first height of the height measured from a first point on the rear surface to a corresponding point on the front surface differs by at least 1 mm from the second height of the height measured from a second point on the rear surface to a corresponding point on the front surface, and the second point is spaced at most 1 mm apart from the first point.

16. The ophthalmic device according to any one of claims 1 to 15, wherein the main body comprises a plurality of ophthalmic lubricants.

17. The ophthalmic device according to claim 16, wherein each of the plurality of ophthalmic lubricants is selected from the group consisting of polyvinyl alcohol, polyol, glycerol, polyethylene glycol, propylene glycol, polysorbate, hyaluronic acid or a pharmaceutically acceptable salt thereof, cellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, dextran, gelatin, polysorbate, hydroxypropylmethylcellulose, and povidone.

18. The ophthalmic device according to any one of claims 1 to 17, wherein the PVOH comprises two or more types of PVOH that are different from each other in terms of chain length, degree of hydrolysis, or both.

19. The ophthalmic device according to claim 18, wherein at least 35 wt% of the two or more PVOHs have a degree of hydrolysis of less than 90%.

20. The ophthalmic device according to claim 16, wherein the ophthalmic lubricant contains polyethylene glycol (PEG), and the mass content of the PEG in the elastomer matrix is ​​approximately equal to the mass content of the PVOH.

21. The ophthalmic device according to claim 16, wherein at least 35% of the ophthalmic lubricant consists of glycerol and propylene glycol.

22. The ophthalmic device according to any one of claims 1 to 21, wherein the elastomer matrix is ​​impregnated with an ophthalmologically acceptable pharmaceutical active ingredient.

23. An ophthalmic device according to any one of claims 1 to 22, which can be obtained by mixing API with water and an ophthalmic lubricant to obtain a mother liquor, and drying the mother liquor at room temperature.

24. The ophthalmic device according to claim 23, which can obtain the mother liquor without heating it.

25. An ophthalmic device according to any one of claims 22 to 24, which can obtain API without heating.

26. The following mechanical properties: a. Tensile strength of 0.05 MPa to 10 MPa, b. Young's modulus from 0.05 MPa to 10 MPa, c. Elongation at break of 50% to 1,000% An ophthalmic device according to any one of claims 1 to 25, characterized by at least one of the above.

27. An ophthalmic device according to any one of claims 1 to 26, configured to lose at least 50% of its weight within two hours within the eye.

28. The ophthalmic device according to any one of claims 1 to 27, wherein the holding portion is configured to hold the ophthalmic device in place when the ophthalmic device is attached and the eye rotates.

29. An ophthalmic device according to any one of claims 1 to 28, wherein a first height measured perpendicular to a reference plane from a first point on the rear surface to a corresponding point on the front surface differs by at least 1 mm from a second height measured perpendicular to a reference plane from a second point on the rear surface to a corresponding point on the front surface, and the second point is spaced a maximum of 1 mm apart from the first point.

30. An ophthalmic device according to any one of claims 1 to 29, having a size and shape such that it is completely covered by the lower eyelid when attached below the lower eyelid.

31. An ophthalmic device according to any one of claims 1 to 30, configured for self-administration.

32. An ophthalmic device according to any one of claims 1 to 31, configured to be worn away from the fornix of the eye.

33. An ophthalmic device according to any one of claims 1 to 32, comprising two or more types of PVOH, wherein each of the two or more types of PVOH accounts for at least 10% of the total amount of PVOH in the matrix.

34. It contains two or more types of PVOH, where one of the two or more types of PVOH has a long chain and is completely hydrolyzed, a. Those having short chains and being partially hydrolyzed, b. Those having long chains and being partially hydrolyzed, c. Those having short chains and being completely hydrolyzed, An ophthalmic device according to any one of claims 1 to 33, comprising one type which is at least one of the following.

35. a. The short-chain monomer units number 200 to 2,000. b. The long-chain monomer units are 2,200 to 5,000. c. The degree of hydrolysis of the completely hydrolyzed PVOH is 97% or higher, and, d. The degree of hydrolysis of partially hydrolyzed PVOH is 95% or less. The ophthalmic device according to claim 34.

36. An ophthalmic device according to any one of claims 1 to 35, comprising two or more types of PVOH, wherein the difference in chain length between the two types of PVOH is at least 1,000, and they have similar degrees of hydrolysis, with each degree of hydrolysis being between 97% and 100%.

37. An ophthalmic device according to any one of claims 1 to 36, comprising two or more types of PVOH, wherein the first of the two or more types has a degree of hydrolysis of 97% to 100%.

38. The ophthalmic device according to claim 37, wherein the second of the two or more types has a degree of hydrolysis of less than 93%.

39. An ophthalmic device according to any one of claims 1 to 38, comprising two or more types of PVOH, wherein the second of the two or more types has a degree of hydrolysis of 80% to 93%.

40. An ophthalmic device according to any one of claims 1 to 39, comprising two or more types of PVOH, wherein the first of the two or more types has a chain length of more than 2,500 units.

41. An ophthalmic device according to any one of claims 1 to 40, comprising two or more types of PVOH, wherein the second of the two or more types has a chain length of less than 1,500 units.

42. An ophthalmic device according to any one of claims 1 to 41, comprising two or more types of PVOH, wherein the ratio between the first type of PVOH and the second type of PVOH among the two or more types is approximately 3:1 to approximately 1:

3.

43. An ophthalmic device according to any one of claims 1 to 42, comprising two or more types of PVOH, wherein the first of the two or more types has a chain length of more than 2,500 units and a degree of hydrolysis of 97% to 100%, and the second of the two or more types has a chain length of less than 1,000 units and a degree of hydrolysis of 80% to 93%.

44. An ophthalmic device according to any one of claims 1 to 43, comprising two or more types of PVOH, wherein the second type of PVOH accounts for more than 50% of the PVOH.

45. An ophthalmic device according to any one of claims 1 to 44, comprising two or more types of PVOH, wherein at least two types of PVOH determine the decomposition rate of the ophthalmic device.

46. The ophthalmic device according to claim 45, wherein the decomposition rate includes the rate at which a predetermined change occurs in predetermined mechanical properties in simulated tears (STF).

47. The ophthalmic device according to any one of claims 1 to 46, wherein the total mass content of the PVOH and the one or more organic plasticizers is at least 70 wt% of the total weight of the matrix excluding the water.

48. The ophthalmic device according to any one of claims 1 to 47, characterized in that the elastomer matrix exhibits substantially isotropic swelling when immersed in simulated tear solution for 5 minutes at room temperature.

49. The ophthalmic device according to any one of claims 1 to 48, wherein the elastomer matrix swells by less than 50% by volume when immersed in simulated tear solution at room temperature for 5 minutes.

50. The ophthalmic device according to any one of claims 1 to 49, wherein the water accounts for less than 50 wt% of the total mass content of the matrix.

51. An ophthalmic device according to any one of claims 1 to 50, which substantially does not include crosslinking by covalent bonding.

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