Classifications

• • G—PHYSICS
  • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
  • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
  • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
  • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
  • G09B23/30—Anatomical models
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
  • A61F2/02—Prostheses implantable into the body
  • A61F2/14—Eye parts, e.g. lenses or corneal implants; Artificial eyes
  • A61F2/16—Intraocular lenses
  • A61F2/1613—Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus
  • A61F2/1616—Pseudo-accommodative, e.g. multifocal or enabling monovision
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0048—Eye, e.g. artificial tears
  • A61K9/0051—Ocular inserts, ocular implants

Definitions

• the present invention relates to an osmotic device for physiological applications, such as an improved delivery system for the time release of physiologically active agents, and an improved lens system which utilizes fluid as its primary lens medium.
• U. S. Patent No. 3,832,458 reveals a device in which a silicon polymer wall is utilized to vary permeability to an internal active agent. The permeability is adjusted by fabricating the wall with varying amounts of N-vinyl-pyrrolidone. While this device represents an improved drug delivery technique, it has a significant disadvantage in that it represents a the driving force of drug delivered to the outside is the result of the internal concentration of drug alone. Thus the drug will be delivered at an initial rapid rate fol ⁇ lowed by a significantly lower rate until the active agent is expended.
• U.S. Patent No. 4,309,996 by Theeuwes discloses a somewhat different mechanism for delivery of drugs whereby a separate compartment filled by a net osmotic inflow is utilized to expand against a flexible internal partition which forces the active agent out of a second compartment through a microporous structure thus attempt ⁇ ing to approximate a steady delivery rate.
• the osmotic device of the present invention overcomes these drawbacks by providing a drug delivery system which is flexible in that there are numerous variables which can be modified to control the delivery rate of the drug.
• an improved lens is provided which utilizes fluid as its primary lens medium.
• the osmotic device according to the present invention is especially suited for use as an ocular lens, and the present invention further includes an improved method for the insertion of such an ocular lens.
• the ideal lens would utilize body fluids, such as lachrymal fluids, to form the desired lens and therby completely eliminate the need for intro ⁇ duction of foreign material into the eye.
• body fluids such as lachrymal fluids
• OMPI the configuration of the device to a cornea by utilizing an insert filled with physiologically compatible fluid such as lachrymal fluid.
• physiologically compatible fluid such as lachrymal fluid.
• the lens utilizes a soft contact material, not the fluid, as the primary lens medium.
• Another object of the present invention is to provide a physiological lenticule capable of being introduced into the substance of the cornea with minimal disruption of its normal physiology while at the same time, altering significantly its shape and refractive power.
• Yet another object of the present invention is to provide a new and improved method of placing a lens in the eye by insertion through a minimal incision.
• the present invention provides, in its broadest aspect, an osmotic device for immersion in a physiological fluid.
• the device includes a semipermeable sheath defining a fully enclosed cavity and being i per- forate except for a plurality of pores for permitting the flow of the physiological fluid into the cavity.
• At least one macromalocule is located within the cavity and has a size that is larger than the pores in the sheath so that the macromolecule is prevented from leaving the cavity when the osmotic device is immersed in the physio ⁇ logical fluid whereupon the physiological fluid surround ⁇ ing the sheath is allowed to flow into the cavity through the pores under the influence of osmotic pressure and the molecular concentration of the physiological fluid within the sheath is maintained greater than the molecular concentration of the physiological fluid outside the sheath.
• a system for the controlled delivery of a physiologically active agent to a fluid environment comprising a semipermeable sheath having a plurality of pores and being imperforate except for the plurality of pores and defining a fully enclosed cavity for holding a physiologically active agent.
• a physiologically active agent is contained in the fully enclosed cavity for delivery to a fluid environment, the plurality of pores being sized to permit both the flow of fluid from the fluid environment through the semipermeable sheath into the cavity and the flow of fluid and physiologically active agent in solution out of the cavity to the fluid environment whereby the physiologically active agent is delivered from the semipermeable sheath exclusively through the plurality of pores.
• a lens comprising a semipermeable transparent sheath having opposite anterior and posterior portions joined at their edges and forming a closed interior space between themselves.
• a body of liquid is provided within the sheath, fills the interior space and constitutes a lens whose anterior and posterior surfaces are bounded by the anterior and posterior portions of the sheath, respectively.
• Means are provided, in the body of liquid for producing within the interior space a concentration which is greater than the concentration of a liquid medium in association with which the lens is to be used, in consequence of which when the lens is in contact with such medium, the interior space will be kept filled with liquid under the influence of osmosis which causes the flow of liquid from the exterior of the sheath to the interior thereof, whenever the interior space is less than full.
• An alternative embodiment of the present invention provides a lens in the form of a contact lens comprising a concave semipermeable transparent element adapted to seat on a human cornea to form therewith a ' closed interior space which contains a body of physiolog- ical solution produced by the wearer of the element and the body of liquid constitutes an optical lens whose anterior surface is bounded by the element and whose posterior surface is bounded by the cornea of the wearer.
• Means carried by the element at its interior is provided for producing within the interior space, when the same contains the body of liquid, a concentration which is greater than the concentration of the physiological solution produced by the wearer of the contact lens, in consequence of which when the element is worn on the cornea, the interior space will be kept filled with liquid under the influence of osmosis which causes the flow of liquid from the exterior of the space to the interior thereof whenever the interior space is less than full.
• the present invention provides a method of locating an intraocular lens into an eye comprising the steps of providing a dehydrated semiper ⁇ meable transparent sheath having opposite anterior and posterior portions joined at their edges and forming a closed interior space between themselves and means within the interior space for producing within the interior spacing a concentration which is greater than the concen- tration of the physiological solution produced by the wearer of the lens, in consequence of which when the sheath is worn by the wearer, the sheath will hydrate such that the interior space will be kept filled with liquid under the influence of osmosis and therby form a lens, making an incision for insertion of the dehydrated semipermeable sheath into the eye and then inserting the dehydrated semipermeable sheathing into the eye whereby the dehydrated semipermeable sheath will contact the physiological solution produced by the wearer and hydrate to form a lens.
• the osmotic device of the present inven ⁇ tion is particularly suited for an ocular lens, it is also suitable for any lens which is intended to be utilized in a fluid environment.
• the osmotic device of the present invention whether or not it is in the form of a lens, permits the dispensing of physiologically active agents over a sustained period of time when the device is immersed in a physiological fluid BRIEF DESCRIPTION OF THE DRAWINGS
• Figure 1 is a perspective view of a device according to the invention.
• Figure 2 is a sectional view along the section line II-II in Figure 1.
• Figure 3 is a plot of the drug delivery rates of devices according to the invention.
• Figure 4 is a perspective view of an altern ⁇ ative embodiment of a device in the form of a lens according to the invention.
• Figure 5 is a sectional view of the alternative embodiment of the lens shown in Figure 4 in place on the cornea of the wearer.
• Figure 6 is a perspective view of an eye in
• OMPI partial section showing an alternative embodiment of the invention partially inserted therein.
• the osmotic device according to the invention will first be described in the context of a delivery system for physiologically active agents.
• an osmotic device 10 which is generally of circular configuration, but whose shape may vary as appropriate for differing sites of application, consists of a semipermeable sheath 19 which is made of two thin sheets 12 and 14. The thin sheets 12 and 14 are bound along their espective edges to form a sheath with an outside edge 16.
• the osmotic device when employed as a delivery system according to the invention, is intended to be used in a fluid environment with sufficient fluid present to enable the system to operate as intended.
• the system according to the invention is particularly suitable for the delivery of active agents to animals and may be located with respect to the animal to be treated by positioning or implanting the system in a variety of locations such as the animals rectum or gastrointestinal tract, etc.
• thin sheets 12 and 12 are particularly suitable for the delivery of active agents to animals and may be located with respect to the animal to be treated by positioning or implanting the system in a variety of locations such as the animals rectum or gastrointestinal tract, etc.
• Thin sheets 12 and 14 define a cavity 18 which is intended to contain a physiologically active agent.
• Thin sheets 12 and 14 are provided with a plurality of pores in order to be semi ⁇ permeable and permit the passage of fluid therethrough.
• the present invention utilizes the principle of osmotic flow which results from a difference in molecular concentration being present across a semipermeable membrane.
• cavity 18 will contain at least a physiologically active agent which will go into solution with fluid which will enter cavity 18.
• the physiologically active agent may or may not be fully soluble as long as it can be delivered from device 10 at a suitable and predictable rate.
• a macromolecule is also present in cavity 18.
• the term macromolecule is intended to mean a large molecule such as a protein, carbohydrate, rubber or other natural or synthetic higher polymer.
• This flow of fluid results from the net higher molecular concentration or net higher osmotic pressure which is present in cavity 18 due to the presence of a physiologically active agent alone or the physiologically active agent and the macromolecule. That is, the body of fluid inside the semipermeable sheath is hypertonic with respect to the fluid outside of the semipermeable sheath, i.e., the fluid inside the semipermeable sheath has a higher osmotic pressure than the fluid outside the semipermeable sheath.
• the osmotic pressure inside cavity 18 will be higher than that of the fluid surrounding the device and, therefore, there will be a net inward flow of fluid.
• fluid continuously enters and leaves cavity 18 which results in a dispersion of the active agent from cavity 18.
• the net inflow of fluid volume will occur in the initial states under the influ ⁇ ence of osmosis until the osmotic pressure and fluid inflow result in the device achieving its natural pre- li molded configuration.
• the burst strength of the encapsu ⁇ lating polymer film and its seal exceed the maximum achievable osmotic pressure by at least several orders of magnitude.
• the continuing steady-state flux of fluid across the walls of the device will result in the disper ⁇ sion of any active agent whose molecular size is such as to allow passage through the preselected pore diameter of the membrane wall.
• the osmotic flow which results due to molecular concentration differences is independent for each mole ⁇ cule involved.
• A macromolecule
• B another molecule
• molecule B would set up a concentration gradient across the semipermeable sheath independent of the gradient present as a result of macromolecule A.
• the osmotic flow resulting from the presence of molecule B would be independent of the osmotic flow resulting from the presence of macromolecule A.
• a macromolecule would be complexed with the physiological agent and the macromolecule selected such that it would be larger than the pores of the semipermeable sheath, yet the complex would decay over a period of time thereby allowing the active agent to slowly disperse from the semipermeable sheath.
• the macromolecule may be selected from any class of compounds with olecu- la weight and configuration sufficiently large to be excluded passage of the desired pore size. Generally suitable are the dextrans, amylopectins (hydroxyethyl- starch), polyvinylpyrrolidone , polyethylene glycol, albumin and various other soluble polymers and/or pro- teins. Alternatively, emulsions with droplets containing active agent can be utilized as well. Microemulsions with droplets of a diameter range 0.01 to 0.1 microns are transparent and optically clear and thus, preferable for optical systems whereas macroemulsions with droplet of size 0.1 to 1 or 2 micrometers may be satisfactory in other uses.
• the active agents suitable for use in connec- tion with the present invention include for examples: oxygen, preferentially bound to fluorocarbons; salicy- lates, catechols, halogens, barbiturates or other com ⁇ pounds complexed to a macromolecule such as polyethylene glycols?
• antibiotics such as chloramphenicol, sulfa or other medications complexed with a macromolecule such as polyvinylpyrrolidone; antiepileptic medications such as phenytoin complexed to albumin; antihistamines, quinine, procaine or other compounds complexed to a macromolecule such as sodium carboxymethylcellulose; salicylates complexed to the antibiotics oxytetracycline or tetracy- cline or other compounds complexed to a macromolecule such as salicylates or other macromolecules could be utilized such as caffeine or albumin.
• the above identi ⁇ fied complexes have well known dissociation constants. See generally Remington's Pharmaceutical Sciences, 16th Edition, Arthur Osol, Editor, Mack Publishing Co. 1980, pp. 182-193 and Physical Pharmacy, 2d Edition, Martin et al. Lea & Febiger, 1969, pp. 325-352.
• a given delivery rate of active agent and/or complexing molecule can be achieved through selection of appropriate membrane pore size, density, environmental conditions and binding molecule.
• Active agent and binding molecule form a molecular complex with an affin ⁇ ity for each other which can be expressed as a dissocia- tion constant, an easily determined quantity related to concentration and physiocochemical environment. This constant is directly proportional to the concentration of the complex and inversely proportional to the product of the concentrations of active agent uncomplexed and binding molecule uncomplexed. It can thus be seen that if a nondiffusable binding molecule is chosen, the further dampening of a potentially rapid or exponential rate of delivery of active agent can be achieved.
• the dissociation constant is represented as K
• the molar concentration of the drug as (D)
• B binding molecule concentration
• B-D bound complex
• the thickness of the semipermeable sheet material, utilized in connection with the invention, will depend on a number of factors and is directly related to the intended use of the delivery system. Generally, the membrne thickness will range from 5-10 micrometers, depending upon the material used and the intended config- uration and concentration gradient.
• Sheet material could be selected from cellulose acetate, cellulose acetate butyrate, cellulose triacetate, poly-1, 4 butylene terephthalate (such as MYLAR ) , polymethylmethacry- late, polypropylene (such as CRYOVAC ), polystyrene, polyvinyl acetate, polyvinyl chloride, polyvinyl fluoride polyvinylidene chloride (such as SARAN R ), polycarbon- ate or silicon-polycarbonate copolymers (such as NUCLEPORE ) and others.
• poly-1, 4 butylene terephthalate such as MYLAR
• polymethylmethacry- late such as CRYOVAC
• polystyrene polyvinyl acetate
• polyvinyl chloride polyvinyl fluoride polyvinylidene chloride
• SARAN R polycarbon- ate or silicon-polycarbonate copolymers
• NUCLEPORE silicon-polycarbonate copolymers
• the sheet material can be made porous in a variety of ways.
• the technique of nuclear track etching can be used, in which the polymer films are exposed to radioactive decay particles and products and then treated chemically to "etch" permanently the tracks of the particles through the film, thus creating pores of a size and density determined by the exposure time and etching process.
• the particle dose determines the hole density while the pore diameter is a function of etching time.
• the specific particles, dose, etchants, and other conditions to achieve desired pore sizes and density for the aforementioned polymer films are well known in the prior art. See Nuclear Tracks in Solids, Principals and Applications, R. L. Fleischer et al. University of California Press, 1975. For example, polycabonate
• ⁇ ⁇ KE ⁇ r filters (such as NUCLEPORE ) are produced by exposure to U 235 followed by sodium hydroxide etching.
• Polyvinylidene chloride (such as SARAN .) can be made microporous by exposure to fission fragments of Califor- nium 252 followed by etching with potassium permang ⁇ anate at 55 degrees Centrigrade.
• the newer advanced lasers such as frequency-doubled Neodymium-YAG, Excimer, tunable dye or other lasers may be used to produce pores of the desired size and density.
• Pores may also be created by forming membranes as integrated sheets of polymer containing "pore-form ⁇ ers," molecules which subsequently can be leached or dissolved out, leaving a predictable pore size.
• the leaching or dissolution can be accomplished prior to use or so selected to occur in the environment of use.
• certain polymer films made of various polycar ⁇ bonates, polyamides, or polyesters can include such pore formers as lithium carbonate, calcium phosphate, and various polysaccharides, such as mannitol, CARBOWAX , etc.
• microporous paths then fill with a medium, compatible with or identical to the medium of the envir ⁇ onment in which active agent, complexing (binding) molecule and complex are soluable, thus permitting diffusion of active agent and fluid medium out of cavity 18 and the generation of an osmotic gradient across semipermeable sheets 12 and 14.
• the pore size will preferably range between 50 Angstroms diameter to 1,000 Angstroms; however, it may be possible to have pore sizes smaller than 50 Angstroms, if desired.
• the pore size is selected depending on the molecular weight and configuration of the macromolecule. For example, a pore size of approximately 60 Angstroms will exclude a molecule having a molecular weight of about 10,000. A 100 Angstrom pore size will exclude a molecule having a 100,000 molecular weight. The exact three dimensional configuration of the molecules may, of course, produce exceptions. Pore density would be on the order of 10 to 10 per square cm; however, de- pending on the application of the device, pore densities less than 10 per square cm may be used.
• the thin sheets 12 and 14 may be joined at their respective edges to form edge 16 in a variety of ways.
• Various heat and impulse sealers can be used with variations in temperatures, frequency, and times allowing for substantial flexibility depending upon the particular polymer.
• Various one-part and two-part compatible adhesive bonding systems such as EASTMAN 910 ,
• EPON 828 R and 3M CONTACT CEMENT R could also be used.
• some materials are suitable for bonding without using conventional bonding methods.
• vinylidene chloride may be sealed to itself while in the so-called "supercooled” state to form a strong bond without conventional dielectric heat or adhesive methods.
• Osmotic pressures generated in cavity 18 obviously will be significantly less than the burst strength of the semipermeable membranes.
• the pressure generated by the macromolecule will be on the order of less than 0.34 atmosphere (5 pounds per square inch), while, for example, the burst strength of vinylidene chloride 1 mil thick is 30 pounds per square inch.
• a delivery system for the drug phenytoin is constructed by forming a sheath made from planar sheets of polycarbonate membrane, with pore size of 0.015 micrometers, porosity 12 x 10 8 /cm 2 and thickness 6 micrometers.
• the polycarbonate membrane is heated to 220 degrees Cent igrade, and molded by vacuum or pressure to a spherical cap of .6.0 mm diameter with radius of curvature, 6.4 mm.
• a 1/2 mm wide planar circumferential cuff is left about each empty spherical cap. Then,
• the 0 delivery system Placed in the fluid environment of use, the 0 delivery system will fill to its normal volume.
• Figure 3 is a plot of the delivery rate of systems according to the invention comparing the delivery rate of a system containing phenytoin-albumin complex with the delivery rate of a system containing phenytoin 5 alone.
• the system utilizing the drug phenytoin-albumin complex shows that 0.74% of its drug content by weight will have been expended and after one hour a total of 1.7% will have been expended, and so on for the following intervals: 2 hrs, 3.4%; 4 hrs, 0 5.4%; 10 1/2 hours, 12%; 24 hrs, 20.2%; 33 1/2 hrs, 27.2%.
• an identical device containing only phenytoin without albumin will deliver at the identical time intervals as noted above, the following percentages of the initial amount of drug placed in the device: 1/2 hr, 1.47%; 1 hr, 2.97%; 2 hrs, 5.7%; 4 hrs,
• osmotic device 10 when osmotic device 10 is employed as a lens, thin sheets 12 and 14 are made of transparent material and are bound along their respective edges to form sheath 19 which defines cavity 18 for retaining a body of fluid.
• the body of fluid comprises the primary lens medium.
• the primary function of the transparent thin sheets 12 and 14 is not to constitute part of the lens medium, but is to retain the body of
• the lens according to the invention is intended to be used in a fluid environment with sufficient fluid present to enable the lens to operate as intended.
• the body of fluid retained by the sheath formed by the thin trans ⁇ parent sheets 12 and 14 will not necessarily be present when the lens is not being used in its intended environment
• 12 and 14 are provided with a plurality of pores in order to be semipermeable and permit the passage of fluid therethrough.
• the semipermeable thin transparent sheet 12 and 14, when joined to form edge 16 result in a semipermeable sheath.
• the lens utilizes the principle of osmotic flow which results from a difference in molecular concentration being present across a semipermeable membrane.
• cavity 18 will contain at least one macromolecule which will go into solution with the fluid in cavity 18 and the macromolecule along with the fluid in cavity 18 will form the body of fluid which constitutes the lens medium.
• the presence of the macromolecule in solution in the body of fluid in cavity 18 results in a molecular concentration gradient being set up between the body of fluid in cavity
• this molecular concentration gradient results in a net flow of fluid from the fluid environment through semipermeable sheath 19 into cavity 18, because the fluid inside the semipermeable sheath has a higher osmotic pressure than the fluid outside the semipermeable sheath due to the presence of the macromolecule in cavity 18.
• the macromolecule and semipermeable sheath are selected such that the macromolecule will not flow is out of cavity 18 through the semipermeable sheath, yet the semipermeable membrane will permit the flow of fluid from the environment in which the lens, is used into cavity 18. Because the macromolecule cannot leave cavity 18, the molecular concentration inside cavity 18 and the molecular concentration outside cavity 18 will never equalize. Since, normally, osmotic flow will continue until the molecular concentrations are equalized, there is always a tendency for the surrounding fluid to flow through the semipermeable sheath. The size of cavity 18, however, is determined by sheath 19, and the tensile strength of sheath 19 is stronger than the osmotic pressure exerted due to the molecular concentration differences. Cavity 18 thus always remains full when disposed in its intended environment.
• the surrounding fluid environ ⁇ ment will generally consist of lachrymal fluid and cavity 18 will fill with such lachrymal fluid.
• aqueous humor will surround the lens and be at an equilibrium with the intralenticular fluid.
• the interstitial fluid of the cornea will comprise the fluid within cavity 18.
• the macromolecule should generally be photostable and inert to assure proper performance of the lens.
• the macromol ⁇ ecule may be selected from any class of compounds with molecular weight and configuration sufficiently large to be excluded passage by the desired pore size. Generally suitable are the dextrans, amylopectins (hydroxyethyl- starch), polyvinylpyrolidone, polyethylene glycol and various other soluble polymers, proteins and/or physiolog ⁇ ically active agents.
• Osmotic device 10 may serve the dual function of a lens as well as a delivery system due to the princi ⁇ ple that, as discussed above, the osmotic flow which results from molecular concentration differences is
• a lens according to this aspect of the invention can be utilized for the delivery of physiological agents by incorporating such agents within cavity 18 and selecting the active agent such that it has a molecule size sufficiently small to pass through the semipermeable sheath.
• a second macromolecule would be tagged with the physiolog ⁇ ical agent and the macromolecule selected such that it would be larger than the pores of the semipermeable sheath, yet it would decay over a period of time thereby allowing the active agent to slowly disperse from the semipermeable sheath. All the while, however, the first macromolecule, which is larger than the pore size of the semipermeable sheath, is confined within cavity 18. Because of the osmotic pressure generated by the first macromolecule, as soon as any active agent leaves the cavity, the surrounding fluid will still enter cavity 18 to maintain the lens configuration.
• the active agents suitable for use in connec- tion with the lens of the present invention include for example: oxygen, preferentially bound to fluorocarbons; salicylates, catechols, halogens, barbiturates or other compounds complexed to a macromolecule such as polyethyl ⁇ ene glycols; antibiotics such as chloramphenicol, sulfa or other medications complexed with a macromolecule such as polyvinylpyrrolidone; antihistamines, quinine, pro- caine or other compounds complexed to a macromolecule such as sodium carboxymethylcellulose; salicylates complexed to the antibiotics oxytetracycline or tetracy- cline or other compounds complexed to a macromolecule such as salicylates or other macromolecules could be utilized such as caffeine or albumin.
• a macromolecule such as polyethyl ⁇ ene glycols
• antibiotics such as chloramphenicol, sulfa or other medications complex
• the delivery rate of active agent and/or complexing molecule is determined as previously discussed in connection with the osmotic device as employed is a delivery system.
• the membrane thickness will generally range from 5-10 micrometers, again depending upon the material used and the desired configuration and concentration gradient intended to be utilized.
• the sheet material for sheath 19 is the lens embodiment could be selected from among the same mater ⁇ ials listed above relative to the use of the osmotic device as a delivery system, and the same processes as described above may be used to create the pores in the transparent sheets and to join the respective edges to form edge 16. Also, the pore size will preferably be the same as previously discussed.
• the refractive index of the lens will be determined by composition and concentration of the body of liquid formed in cavity 18.
• dilute solutions of dextran (average molecular weight 75,000) and amylopectin have a refractive index similar to that of plain water or saline solution, 1.336. (Amylopectin average molecular weight, 545,167).
• a 17% solution of amylopectin has a refractive index of 1.432.
• Lens 20 of Figure 4 is made of a thin transparent sheet 21 of semipermeable material as previously described. While the lens of Figure 4 is an ocular contact lens having a generally circular configur ⁇ ation, the principles of the invention are equally applicable to lenses of other shapes or other uses. Furthermore, while the lenses shown in Figures 3 and 4 are hyperopic contact lenses, the present invention is likelwise suitable for myopic contact lenses. As the anterior surface is regular and independent of the posterior curvature, it will neutralize corneal astigma ⁇ tism and/or irregularity.
• Lens 20 includes scaffolding 29 on the rear surface of the semipermeable sheet 21.
• the scaffolding 29 serves to give additional support to sheet 21.
• OMPI - Scaffolding 29 comprises polymethylmethacrylate, polypro ⁇ pylene, cellulose acetate butyrate, hydroxymethylmetha- crylate or other rigid, semirigid or soft polymer strands.
• Scaffolding 29, as shown in Figure 4 is fish net in configuration; however, it may be a variety of designs such as concentric rings connected by radial spokes, arcuate crossing elements, radial strands, a mesh of criss-crossing meridional fibers, etc.
• scaffolding 29 is shown in connection with contact lens 20 of Figure 4 and 5, it could also be used in connection with other lenses, in accordance with the invention, such as the lens shown in Figures 1 and 2.
• the scaffolding may be joined to the lens by known prior art methods such as by heat impulse sealing, adhesives, or during the manufacturing of the semipermeable sheath.
• lens 30 is shown, in place, on the cornea of the wearer.
• Figure 5 shows a human eye including a cornea 41, iris 42, eye lens 43, anterior chamber 44, posterior chamber 47 and posterior capsule 49.
• Thin transparent sheet 31 rests on cornea 41 and retains a body of fluid 33 which functions as the primary lens medium.
• the body of fluid 33 contains a macromolecule and has a higher concentration than the surrounding ocular fluid, primarily lachrymal fluids. Because the body is of higher concentration than the surrounding body fluids, the cavity defined by the thin, transparent sheet 31 and the cornea 41 will remain filled with fluid.
• contact lens 30 includes a larger diameter outer portion 35 made of soft permeable material which serves as a lens carrier to support contact lens 30.
• the lenses, according to the invention could utilize both scaffolding and a lens carrier if desired. 2*2
• Figure 6 shows an intraocular lens 50 in 'accordance with the invention partially inserted in the eye cavity.
• Lens 50 is provided with haptic support struts which serve to anchor the lens to the eye cavity.
• the lens may be folded or rolled to a size smaller than its hydrated size. This permits the use of a small incision as compared with prior art methods of insertion and results in lessened trauma to the patient.
• the dehydrated lens Once the dehydrated lens is inserted in the eye, it can be unfolded or unrolled and then permitted to hydrate in order to function as a lens.
• Example I A contact lens according to this embodiment of the invention may be constructed for a moderately far- sighted patient after a cataract extraction, a moderately extreme example of need for hyperopic or "+" correction of +14.00 diopters.
• a semipermeable sheath of polyvinyl- idene chloride is provided which has been exposed to Californium 252 to create a pore density of about 10,000 pores per square cm and then etched in potassium per ⁇ manganate at 55 degrees Centigrade for a time appropriate to create a pore diameter of 100 Angstroms.
• a refractive index of 1.366 is arbitrarily chosen and will require a solution of 20% amylopectin.
• a wide and generous optical zone of 7.0 mm is selected.
• the lens is designa ⁇ ted to be fitted to a cornea so that its posterior radius will conform, for example, with an average 7.8 mm radius of the cornea. Given these parameters, an anterior curvature of the lens of 6.0 mm radius will occur and result in an extremely favorable thin lens having a central maximum thickness of the lens of 0.3 mm.
• the volume of the lens will be 6.19 mm and thus 1.5 mg of amylopectin will create the desired 20% solution and refractive index of 1.366.
• the periphery of the lens can be heat-sealed at 225-260 degrees Fahrenheit.
• a posterior scaffolding can be constructed of polymethylmethacrylate, a silicon polymethylmethacrylate polymer, polypropylene or hydrogel and joined to either posterior and/or anterior polymer films by heat impulse, compatible adhesive or the manufacturing process itself when mesh and/or film are in a precast state.
• Example II
• a concave lens to correct high myopia, thus gaining "minus" power can be similarly constructed.
• a lens correcting relatively extreme myopia of -10.00 diopters can be constructed.
• a cornea of average radius of 7.8 mm choosing a refractive index for the lens of 1.366 equalling the index ascertained for a 20% solution of amylopectin, and a large optical zone of 7.0 mm diameter, the required anterior radius of the lens will be 9.9 mm.
• this type of lens it can be con ⁇ structed with no significant center point thickness except for the thickness of the opposing membranes, thus attaining a maximum vertical height at its lateral thickest portion of 0.19 mm.
• the volume of this lens is
• a lens for incorporation within the corneal substance can be similarly constructed.
• the following conditions are assumed: an example of aphakic hyperopia; the need to generate a total ocular power from the posterior corneal surface of 60 diopters; an average normal anterior corneal radius of 7.8 mm; and a posterior corneal radius of 6.5 mm.
• the lens may be made with a dilute solution of acromolecules such that the refractive index approaches that of water and aqueous humor and tears, namely 1.336, less than that of the cornea itself (1.376).
• a large optical zone of diameter of 7.0 mm is chosen and a new anterior corneal radius of 5.6 mm is necessary.
• a lenti ⁇ cule with an anterior radius of 5.35 mm, a posterior radius of 7.55 mm, thus generating a central maximum thickness of 0.4 mm should be fabricated.
• a decreased thickness for any given diameter of optical zone can be achieved by requiring less of a change in the anterior convexity of the cornea.
• Reduction in corneal convexity, by incorpor- ating minus concave lenses for the correction of myopia, can be similarly accomplished by fashioning such intra- stromal lenticules as described for the contact lens.
• Support scaffolding can be incorporated into the- anterior and/or posterior surfacs as needed.
• the periphery of this particular lens may be impulse sealed after incor ⁇ poration of less than one-half mg of dextran (less than 5% solution), requiring a peripherally sealed zone of 1/2 to 1 mm for a total 8.0 to 9.0 mm diameter lenticule.
• Example IV An intraocular lens may be constructed in accordance with the invention.
• a lens symmetric ⁇ ally biconvex, and 33-1/3% solution of dextran or amylo ⁇ pectin with a refractive index of 1.400 a generous optical zone for an intraocular lens of 6.0 mm diameter is chosen, thus requiring a radius anteriorly and poster ⁇ iorly of 6.4 mm and creating a total thickness at the center maximum of 1.4 mm.
• the lens will have a volume of
• This lens may be constructed so that it has a 1/2 mm wide circumferential seal which incorporates thin support haptics enabling the lens in its dehydrated state to be folded or rolled and maneuv ⁇ ered into the eye through an incision 3-1/2 long.

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• 1983
  • 1983-09-27 CA CA000437694A patent/CA1206049A/en not_active Expired
  • 1983-09-28 IL IL69854A patent/IL69854A0/xx unknown
  • 1983-09-29 JP JP58503360A patent/JPS59501897A/ja active Pending
  • 1983-09-29 EP EP19830903350 patent/EP0120937A4/en not_active Withdrawn
  • 1983-09-29 WO PCT/US1983/001531 patent/WO1984001297A1/en not_active Application Discontinuation
  • 1983-09-30 ES ES1983286420U patent/ES286420Y/es not_active Expired
  • 1983-09-30 IT IT8312631A patent/IT1208983B/it active

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