CA2115651C - Medicament coated refractive anterior chamber ocular implant - Google Patents
Medicament coated refractive anterior chamber ocular implant Download PDFInfo
- Publication number
- CA2115651C CA2115651C CA002115651A CA2115651A CA2115651C CA 2115651 C CA2115651 C CA 2115651C CA 002115651 A CA002115651 A CA 002115651A CA 2115651 A CA2115651 A CA 2115651A CA 2115651 C CA2115651 C CA 2115651C
- Authority
- CA
- Canada
- Prior art keywords
- implant
- heparin
- anterior chamber
- lens
- eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- 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, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/147—Implants to be inserted in the stroma for refractive correction, e.g. ring-like implants
-
- 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, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/16—Intraocular lenses
- A61F2/1602—Corrective lenses for use in addition to the natural lenses of the eyes or for pseudo-phakic eyes
- A61F2/1605—Anterior chamber lenses for use in addition to the natural lenses of the eyes, e.g. iris fixated, iris floating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0094—Physical treatment, e.g. plasma treatment
-
- 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
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S623/00—Prosthesis, i.e. artificial body members, parts thereof, or aids and accessories therefor
- Y10S623/901—Method of manufacturing prosthetic device
Abstract
A minus power anterior chamber ocular implant for placement in the anterior chamber of a phakic eye having an anatomic lens in situ comprises a negative artificial refracting lens having at least one concave surface, a surface coating which comprises a compatible sulfated polysaccharide medicament coating, such as heparin, and means for positioning the artificial lens in the an-terior chamber of the eye to prevent contact between the implant and the anatomic lens. The implant compensates for refractive errors or creates a specific refraction to assist in visual function and has increased biocompatibility in the anterior chamber of the eye, thereby preventing or mitigating detrimental effects typically associated with the implantation of an uncoated refractive ante-rior chamber implant in the eye. A method of preparing such a minus power anterior chamber ocular implant comprises first ex-posing an uncoated implant to a plasma to generate a plasma-treated implant having a surface containing amines, carboxylic ac-ids, active free radicals or passive free radicals; and thereafter bonding the medicament to the plasma-treated implant surface. A
method of treating myopia comprises surgically implanting and anchoring the implant in the phakic eye to compensate for refrac-tive errors.
method of treating myopia comprises surgically implanting and anchoring the implant in the phakic eye to compensate for refrac-tive errors.
Description
.. , WO 83/03776 ~ ~ ~ ~ ~ ~ ~ PCT/tJS92/06~1 ~
Description Medicament Coated Refractive Anterior Chamber Ocular Implant Background of the-Invention This invention relates to a medicament-coated minus power anterior chamber ocular implant far p~.acem~nt in a phaki'c eye to correct refractive errors such as myopia, a method of preparing such an implant and a method of using such an implant in a myopic phakic human eye.
zt is well known to those skilled in the field of ophthalmology that there has previQUSly been, and continues to be, a need for a successful anterior chamber'ocular implant in the phakic eye to compensate for refractive errors such as high myopia or to create a specific refraction to assist in visual function.
;For example; U.S. Patent No. 4,676,792'(Praeger~
discloses the use of an uncoated anterior chamber minus power lens having a planar anterior-facing surface and a concave posterior-facing surface in the treatment of myopia. In addita,onthe recent use of uncoated implants; as a surgical approach'for patients having high myo~~.a that is not satisfactorily corrected with 2'Q Spectacles or contact- lenses has been attempted in .France, as described in Colin et al,, Refractive and Corneal Surgery, vol: 6 (July/August 1990~e pp. 245-51 and Baikoff et al., Refractive and Corneal Surgery, tlol. 6, (July/August 1990j. PP- 252-~0.
However; it; has"been acknowledged by those skilled in the art that-there are significant risks involved im he use-of such anterior chamber implants in the eye.
For example, when such an implant is'ins~rted into the eye; temporary or permanent adhesions of theiimplant to 'l , .fi , s ...
' ..Y
.3 r.....
".f. ,.,f .4'..-' .. a .' ~7 ,.,.. .
f .rd . r y ,..
,3 w n . " .. . ... .,.
,...v:,:;, . . "...l , ,... "..., . . ...f''..v.r. ". . . ~ "
WD 93103776 PCT/US92/OG,;~18 211~6~1 -2-delicate intraocular structures may result, causing damage to these structures to ensue either immediately or over the long term. In addition, once the implant is in position, it may cause similar adhesions due to mechanical and/or chemical inflammation leading to fibrosis of a progressive nature and damaging of the intraocular tissue, thereby making subsequent removal of the implant a complex, dangerous surgical procedure.
Other problems associated with such implants are cataract formation, secondary glaucoma, corneal edema, hyphema, and progressive endothelial cell loss, in addition to other complications:
As observed in'Ophthalmology Alert, Vol. 1, No. 11 (Nov. 1990), pp. 41.-42, several American manufacturing companies which were preparing to begin clinical trials of anterior chamber ocular implants in the United States are now likely to abandon these studies, due to the attendant risks associated with the implants and the difficulty of obtaining approval of the federal 2U Food and Drug Administration (FDA) for the use of the implants. In view of the foregoing; it would clearly be advantageous to employ a minus power anterior chamber ocular implant having a'campatible medicamer~t coating which would ameliorate and/or prevent the 25' occurrence of the above-described problems associated with such implants.
It xs also well'known to those skilled in the art that an intraocular '~:ens; when surgically inserted, is predominantly designed to replace a previously or 30 simultaneously removed cataractous lens. However, although the implantation of intraocular lenses has constituted an appreciable surgical. advance; such implantation has been known to cause immediate or late damage to the corneal endothelium, immediate or late 35 inflammatoryresponses in the anterior and/or posterior segments of the eye,'immediate or late secondary f. , ~y; .:o'., .
t1'i: ': v.....
...t..::, 'l F . A . ' '.:
Mtd..
l~ W ... .... . .. . . , ~~' :. . .... "~. .. .:.:.. ...~~ .~ :. ,.....~. ," .'.:. . ..'a a " ~...:;.' , . .,:.:;,. . ~ ,:'..' . ' '.:,.., ..'. '~" .; . ;,~; , , '..;:.
WO 93/03776 'Z 1 ~C ~ ~ ~ PCT/US92/06818 _3_ fibrosis and/or neovascularizatioa~, and other problems.
In general, the phakic eye is more reactive than the aphakic eye, i.e. in the phakic eye, inflammatory reac-dons tend to be greater resulting in a concomitant increase in damage to'the eye. Firstly, in the-aphakic eye no lens pulls on the ciliary body; thus the ciliary body is in a "resting state" and tends to undergo some degree of atrophy. Therefore, an inflammatory response will be less in the aphakic eye. Secondly, the phakic 1o eye has a shallower anterior chamber (i.e. the average antero-posterior depth is less) than the aphakic eye, and the iris has a'greater surface area contacting the .' lens. Therefore, if an inflammatory reaction occurs in the phakic eye, there is a greaterlarea of adherence of the iris to the anterior surface of the anatomic lens.
To overcome the above-described problems associated with the use of intraocular lenses to rep~.ace cataractous lenses;vthe use of intraocular ' lenses haying various coatings has previously been disclosed. For example,- U:S. Pat. No. 4,170,043 (Knight et al.) discloses coated intraocular lenses made of an acrylic resin having a coating to prevent adhesion o~-the intraocular Tens to the corneal -endothelium; the coating being polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, dextran, hydroxyethyl starch, methylcellulose or;guar gum. However, some of these coatings have been found to cause inflammatory reactions and have proven to be unsataisfactory in clinical practice.
West German patent application No. 2,556,65 dis-closes coated intraocular lenses wherein the coating is a eilicox~ rubber, such as methyl or methylphenyl ~iloxane. U.S. Pat. No. 4,240,163 (Galin) discloses coated intraocular Iense~ wherein the coating is a compatible medicament such~as sulfated polysaccharide.
W~ 93/03??6 PCT/US92/OG"~.1,~
2~.~.5~~~. ~4-Also, intraocular lenses having a covalent attachment of heparin to a polyamine that is ionically adsorbed onto an intraocular lens surface have been disclosed in product Literature of J~harmacia AB of Uppsala, Sweden entitled "Surface Modified TOLs: A New Approach to Cataract Surgery; ~~ pp. 7.7-19.
A further risk involved in the use of such anterior chamber implants in the eye is the potential for the implanted lens to touch the cornea and/or to 1b contact the anatomic lens and/or the iris with resultant complications. However, the above-mentioned possibility of the lens touching adjacent anatomical structures may be avoided or mitigated by vaulting the lens in such a way as to minimize the chance of this occurrence.
In view of the foregoing, it will be apparent to those skilled in the art that some of 'the problems associated with the use of anterior chamber ocular implants employed to correct refractive errors in the phakic eye differ from those associated with the use of in~raocular lenses employed as replacements for surgically removed cataractous lenses. For example, the use of implants in the phakic eye may actually -cause,cataract formation in the natural lens which rema~.ns in situ, whereas the use of intraocular lenses in, patients having cataract removal cannot induce such an effect, as the natural lens has been replaced by the intraocular l~~s.
It is one object of this inventi~an to provide a minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having an anatomic lens in situ. The implant comprises a negative artificial refracting Lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the s'.;.r~ , :.. ; : ... .. . .: : . ~ . . :: ;. .. - ,., .;.,~.~ ,. .,.;:. .: .
. ::, : _ .:.; ,:: .. .. .,., .,.,1. : .'h. ...
..h. -..~.i ~
.., , ~;.,.,... . ,.'.,: .fna'~:r .. ..'~.~ , .. .,.:,' ~:': .., y'~ , ,:'~ .
':~.. . . ... ~..: . . v' . .:.~,.'. .' ' .'., ..y..,:~ "~..:~ ~'!:, '.,:., iv,., . .. .. ..
r~~, WO 93!03776 a 5 _ _ ~ ~ ~ ~ ~ ~ ~ PCT/US92/Ob818 anterior chamber of the eye to prevent contact between the implant and the anatomic lens. The implant may be surgically implanted in the phakic eye to compensate for refractive errors, which avoids the concomitant problems described above. The implant may subsequently be removed from the eye, if necessary.
It is one feature of this invention that the coata.ng may be bonded covalently, by ionic attraction, or hydrogen bonding to the surface of the implant. It is another feature of this invention that the sulfated polysaccharide coating may be selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid.
It is yet another feature of this invention that the coating may be ~dditianally complexed with compounds having anticoagulation properties ,such as antithrombin. It is yet another feature of this invention that he coating may additionally comprise :20 one or mare compounds capable of absorbing ultraviolet and other short wavelength radiation.
It is one advantage of the coated implant of this invention that it avoids attraction and minimizes the adherence of white blood cells, pigment granules and intraocular tissue to its surface. It is another advantage of this invention that it avoids stimulation of white cell activity and enzyme release which results in corneal endothelial destruction end dysfunction. It is yet another feature of this invention that cataract 3~ formation secondary to surgical trauma and/or short and long erm inflammation may be minimized and/or avoided.
Tt is yet another advantage of this invention that flare, white cells, vitreous reaction, cystoid macular edema, hyopyon, uveitis, and secondary glaucoma typically associated by those skilled in the art with W~ 93/03776 -6- PL'fIUS92/06~18 the use of anterior chamber eys implants may be avoided.
Tt is another object of this invention to provide a method of preparing the above-described minus power anterior chamber ocular implant, wherein the implant avoids the above-discussed problems when it is surgically implanted into the eye, and may subsea~uently be removed from the eye if necessary.
Tt is one feature of the method of preparing such an implant that the coating may be banded covalently, by ionic attraction, or hydrogen bonding to the surface of the implant. It is another feature of this method that the sulfated polysaccharide coating may be selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate,:dermatan sulfate, chitosan sulfa e, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid. It is yet another feature of this method that the coating may be additionally complexed with compounds having anticoagulation ~0 properties; such as antithrombin. It is yet another feature of this method that the coating may additionally comprise onie or more compounds capable of absorbing ultravzole~ and other short wavelength -radiation. Tt is yet another feature of this method that plasma-treating may ffirst be used to treat an uncoated implant~and the medicament may thereafter be bonded' to the plasma-treated surface.
It is ~ne advantage of this method that it avoids attraction and minimizes the adherence of white blood cells, pigment granules and intraocular tissue to its surface. It is another. advantage of this method that it avoids stimulation of white cell activity and enzyme release which results-in corneal endothelial destruction and dysfunction. It is yet another feature of this method that cataract formatian secondary to surgical trauma andjor short and fang term inflammation may be minimized and/or avoided.
It is yet another object of this invention to provide a method of using the coated anterior chamber ocular implant of this invention in the treatment of l0 myopia, wherein the implant is surgically implanted in the phakic eye to compensate for refractive errors, thereby advantageously avoiding the above-described problems. The implant may subsequently be removed from the eye, if necessary.
15 Summary of the Invention This invention is directed to a minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having an anatomic lens in situ.. The implant comprises a negative artificial 20 refracting lens having at least one concave surface and a surface coating comprising a compatible sulfated polysaccharide medicament, and mean's far positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic 25 lens.
The sulfated polysaccharide is preferably selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfonated 30 hyaluronic acid, with heparin being particularly preferred. The heparin typically has a molecular weight in the range of about 2,500-15,000 daltons, preferably about 2,500-10,000 daltons, most preferably abut 2,00-5,300 daltons. uhe coating is preferably 35 bonded to the surface of the implant by means of ionic . . .. , . , , , , ., ' . : :.~ , .... -. .. . v . w. '. ', . :' ., .. . .
W~ ~3/03~77 _~- PCT/US92/06R.~8 2~.15~~~
attraction, hydrogen bonding, or covalent banding with covalent bonding being particularly preferred: The coating typically has a thickness in the range from about 1/100,OOOmm to 1/100mm, and constitutes from about 1/10,000% to about 1/10% by weight of the implant. The coating may additionally be complexed with compounds having anticoagulation properties such as antithrombin.
The coated minus power anterior chamber ocular implant of this invention is advantageous in that it may be implanted in the phakic eye to compensate for refractive errors, yet has increased biocompatibility in the anterior chamber of the eye, and thus avoids the problems typically associated with such implantation, including damage to the corneal endothelium, inflammatory responses in the anterior or posterior segments of the eye, particularly the formation of cataracts ~.n the natural lens which is left in situ vwhen the refractive anterior chamber~implant is placed 0 in the eye.
This invention i~ further directed to the method of preparing such a c~ated minus power anterior chamber ocular imglant, themethod comprising the steps of first exposing an uncoated surface of the implant to a ~lasrna to generate a plasma-treated implant having a surface having constituents selected from the group consisting of amines, carboxylic acids, active free radicals, and passive free radicals, and thereafter bonding the sulfated polysaccharide medicament to the plasma-treated implant surface.
This invention is,also directed to a method of treating myopia comprising surgically implanting and anchoring in the anterior chamber of a phakic eye the coated minus power anterior chamber ocular implant of this invention.
..7 .r... " ..:.r 5 ... ~:.~ . . .. ' ...y t ; :;~ V ..:.,, .:.; , ,.:. . :::
. '.~ .:' ., r'. 7 . .. , '. . .. '... : : ' '.. ' ;., ' ,: . . ., : '. ' .,' . ' '.
., 5;~ r .... ,." . .~::.. . . . :1.: ;., ....~~. .~ ~ .....:...., .,......
.~. . ,.: . . .. '..:,.. ~ ........~...,'.. ..,..,;:.. . ,~.....~..
.....:n ... ... .,... .W..~... ...(...,~y n.... .:'.... ..:. ~_;.y ,:~,...,~~
....'. .,... .,.,.;.y. ..,..... : . ... .- .. ....
. . ... . v.... ( ? ! . , . . . . .'. ' ...
~,~ W~ 13103776 ~ 1 ~ ~ ~ ~ PCTIUS92/06~18 _g_ . ~
Erief Description of the Drawings The anterior chamber ocular implant of the present invention will hereinafter be described with reference, in part, to the accompanying drawings, in which:
Figure 2 is top plan view of one embodiment of an anterior chamber ocular implant in accordance with the present invention, wherein the negative refracting lens is biconcave.
Figure 2 is a side cross-sectional view of an eye containing the biconcave implanted anterior chamber ocular implant of Figure 1.
Description of the Preferred Embodiments This invention is directed to a minus power anterior chamber ocular implant for placement in tha anterior craamber of an eye having an anatomic lens in situ. As used ire this description and in the appended claims, the term 'minus power anterior chamber ocular implant' refers specifically to a negative refracting lens,surgically implanted in the phakic eye to compensate for and/or correct refractive errors, and specifically excludes intraocular lenses which are surgically inserted in the aphakic eye, such as are disclosed, for example, in U.S. Pat. No. 4,240,163 (Galin) The negative refracting lens employed in the present invention his a lens shape with two refractive surfaces, at least ane of which is concave, such that the combined refractive powers of the two surfaces is a minus or negative.' Such lenses are typically employed to correct high myopia.
As discussed hereinabove, uncoated minus power anterior chamlber ocular implants are well known to those skilled in the art: The optical portion of the implant employed in the present invention is preferably fabricated from compounds such as polymethyl -1~°
methacrylate, poly-2- hydroxyethyl methacrylate, methyl methacrylate copolymers, siloxanylalkyl, fluoroalkyl and aryl methacrylates, silicone, silicone elastomers, polysulfones, polyvinyl alcohols, polyethylene oxides, copolymers of fluoroacrylates and methacrylates, and polymers and copolymers of hydroxyalkyl methacrylates, such as 2-hydroxyethyl methacrylate, glyceryl methacrylate, 2-hydroxypropyl methacrylate, as well as methacrylic acid, acrylic acid, acrylamide methacrylamide, N,N-dimethylacrylamide, and N-vinylpyrrolidone. Additionally, compounds which absorb ultraviolet or other short wavelength (e. g.
below about 400 nm) radiation, such as compounds derived from benzotriazole groups, benzophenone groups, or mixtures thereof may be added to the monomers and/or polymers which constitute the anterior chamber ocular implant. Other compounds well known to those skilled in the art may also be used in fabricating the anterior chamber ocular implant employed in this invention.
It is well known to these skilled in the art that when positioning an implant within the anterior chamber of the phakic eye, it is important to avoid, inter alia, contact between the implant and the anatomic lens residing in the posterior chamber. In the present invention, haptics are integral to the optical portion of the implant, and position or "vault"
the artificial lens in the anterior chamber of the eye to prevent such contact. The haptic;s may be of the same material as described above for the optical por-tion of the implant, or may be made of materials such as polypropylene. Haptics which may be employed in the implant of the present invention include haptirs such as disclosed in U.S. Patent No. 4,676,792 (Praeger), Most minus power anterior chamber implants typi-cally have an overall diameter of approximately 12-14 ,;., .
f..:
. , ...
,,:
Description Medicament Coated Refractive Anterior Chamber Ocular Implant Background of the-Invention This invention relates to a medicament-coated minus power anterior chamber ocular implant far p~.acem~nt in a phaki'c eye to correct refractive errors such as myopia, a method of preparing such an implant and a method of using such an implant in a myopic phakic human eye.
zt is well known to those skilled in the field of ophthalmology that there has previQUSly been, and continues to be, a need for a successful anterior chamber'ocular implant in the phakic eye to compensate for refractive errors such as high myopia or to create a specific refraction to assist in visual function.
;For example; U.S. Patent No. 4,676,792'(Praeger~
discloses the use of an uncoated anterior chamber minus power lens having a planar anterior-facing surface and a concave posterior-facing surface in the treatment of myopia. In addita,onthe recent use of uncoated implants; as a surgical approach'for patients having high myo~~.a that is not satisfactorily corrected with 2'Q Spectacles or contact- lenses has been attempted in .France, as described in Colin et al,, Refractive and Corneal Surgery, vol: 6 (July/August 1990~e pp. 245-51 and Baikoff et al., Refractive and Corneal Surgery, tlol. 6, (July/August 1990j. PP- 252-~0.
However; it; has"been acknowledged by those skilled in the art that-there are significant risks involved im he use-of such anterior chamber implants in the eye.
For example, when such an implant is'ins~rted into the eye; temporary or permanent adhesions of theiimplant to 'l , .fi , s ...
' ..Y
.3 r.....
".f. ,.,f .4'..-' .. a .' ~7 ,.,.. .
f .rd . r y ,..
,3 w n . " .. . ... .,.
,...v:,:;, . . "...l , ,... "..., . . ...f''..v.r. ". . . ~ "
WD 93103776 PCT/US92/OG,;~18 211~6~1 -2-delicate intraocular structures may result, causing damage to these structures to ensue either immediately or over the long term. In addition, once the implant is in position, it may cause similar adhesions due to mechanical and/or chemical inflammation leading to fibrosis of a progressive nature and damaging of the intraocular tissue, thereby making subsequent removal of the implant a complex, dangerous surgical procedure.
Other problems associated with such implants are cataract formation, secondary glaucoma, corneal edema, hyphema, and progressive endothelial cell loss, in addition to other complications:
As observed in'Ophthalmology Alert, Vol. 1, No. 11 (Nov. 1990), pp. 41.-42, several American manufacturing companies which were preparing to begin clinical trials of anterior chamber ocular implants in the United States are now likely to abandon these studies, due to the attendant risks associated with the implants and the difficulty of obtaining approval of the federal 2U Food and Drug Administration (FDA) for the use of the implants. In view of the foregoing; it would clearly be advantageous to employ a minus power anterior chamber ocular implant having a'campatible medicamer~t coating which would ameliorate and/or prevent the 25' occurrence of the above-described problems associated with such implants.
It xs also well'known to those skilled in the art that an intraocular '~:ens; when surgically inserted, is predominantly designed to replace a previously or 30 simultaneously removed cataractous lens. However, although the implantation of intraocular lenses has constituted an appreciable surgical. advance; such implantation has been known to cause immediate or late damage to the corneal endothelium, immediate or late 35 inflammatoryresponses in the anterior and/or posterior segments of the eye,'immediate or late secondary f. , ~y; .:o'., .
t1'i: ': v.....
...t..::, 'l F . A . ' '.:
Mtd..
l~ W ... .... . .. . . , ~~' :. . .... "~. .. .:.:.. ...~~ .~ :. ,.....~. ," .'.:. . ..'a a " ~...:;.' , . .,:.:;,. . ~ ,:'..' . ' '.:,.., ..'. '~" .; . ;,~; , , '..;:.
WO 93/03776 'Z 1 ~C ~ ~ ~ PCT/US92/06818 _3_ fibrosis and/or neovascularizatioa~, and other problems.
In general, the phakic eye is more reactive than the aphakic eye, i.e. in the phakic eye, inflammatory reac-dons tend to be greater resulting in a concomitant increase in damage to'the eye. Firstly, in the-aphakic eye no lens pulls on the ciliary body; thus the ciliary body is in a "resting state" and tends to undergo some degree of atrophy. Therefore, an inflammatory response will be less in the aphakic eye. Secondly, the phakic 1o eye has a shallower anterior chamber (i.e. the average antero-posterior depth is less) than the aphakic eye, and the iris has a'greater surface area contacting the .' lens. Therefore, if an inflammatory reaction occurs in the phakic eye, there is a greaterlarea of adherence of the iris to the anterior surface of the anatomic lens.
To overcome the above-described problems associated with the use of intraocular lenses to rep~.ace cataractous lenses;vthe use of intraocular ' lenses haying various coatings has previously been disclosed. For example,- U:S. Pat. No. 4,170,043 (Knight et al.) discloses coated intraocular lenses made of an acrylic resin having a coating to prevent adhesion o~-the intraocular Tens to the corneal -endothelium; the coating being polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, dextran, hydroxyethyl starch, methylcellulose or;guar gum. However, some of these coatings have been found to cause inflammatory reactions and have proven to be unsataisfactory in clinical practice.
West German patent application No. 2,556,65 dis-closes coated intraocular lenses wherein the coating is a eilicox~ rubber, such as methyl or methylphenyl ~iloxane. U.S. Pat. No. 4,240,163 (Galin) discloses coated intraocular Iense~ wherein the coating is a compatible medicament such~as sulfated polysaccharide.
W~ 93/03??6 PCT/US92/OG"~.1,~
2~.~.5~~~. ~4-Also, intraocular lenses having a covalent attachment of heparin to a polyamine that is ionically adsorbed onto an intraocular lens surface have been disclosed in product Literature of J~harmacia AB of Uppsala, Sweden entitled "Surface Modified TOLs: A New Approach to Cataract Surgery; ~~ pp. 7.7-19.
A further risk involved in the use of such anterior chamber implants in the eye is the potential for the implanted lens to touch the cornea and/or to 1b contact the anatomic lens and/or the iris with resultant complications. However, the above-mentioned possibility of the lens touching adjacent anatomical structures may be avoided or mitigated by vaulting the lens in such a way as to minimize the chance of this occurrence.
In view of the foregoing, it will be apparent to those skilled in the art that some of 'the problems associated with the use of anterior chamber ocular implants employed to correct refractive errors in the phakic eye differ from those associated with the use of in~raocular lenses employed as replacements for surgically removed cataractous lenses. For example, the use of implants in the phakic eye may actually -cause,cataract formation in the natural lens which rema~.ns in situ, whereas the use of intraocular lenses in, patients having cataract removal cannot induce such an effect, as the natural lens has been replaced by the intraocular l~~s.
It is one object of this inventi~an to provide a minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having an anatomic lens in situ. The implant comprises a negative artificial refracting Lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the s'.;.r~ , :.. ; : ... .. . .: : . ~ . . :: ;. .. - ,., .;.,~.~ ,. .,.;:. .: .
. ::, : _ .:.; ,:: .. .. .,., .,.,1. : .'h. ...
..h. -..~.i ~
.., , ~;.,.,... . ,.'.,: .fna'~:r .. ..'~.~ , .. .,.:,' ~:': .., y'~ , ,:'~ .
':~.. . . ... ~..: . . v' . .:.~,.'. .' ' .'., ..y..,:~ "~..:~ ~'!:, '.,:., iv,., . .. .. ..
r~~, WO 93!03776 a 5 _ _ ~ ~ ~ ~ ~ ~ ~ PCT/US92/Ob818 anterior chamber of the eye to prevent contact between the implant and the anatomic lens. The implant may be surgically implanted in the phakic eye to compensate for refractive errors, which avoids the concomitant problems described above. The implant may subsequently be removed from the eye, if necessary.
It is one feature of this invention that the coata.ng may be bonded covalently, by ionic attraction, or hydrogen bonding to the surface of the implant. It is another feature of this invention that the sulfated polysaccharide coating may be selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid.
It is yet another feature of this invention that the coating may be ~dditianally complexed with compounds having anticoagulation properties ,such as antithrombin. It is yet another feature of this invention that he coating may additionally comprise :20 one or mare compounds capable of absorbing ultraviolet and other short wavelength radiation.
It is one advantage of the coated implant of this invention that it avoids attraction and minimizes the adherence of white blood cells, pigment granules and intraocular tissue to its surface. It is another advantage of this invention that it avoids stimulation of white cell activity and enzyme release which results in corneal endothelial destruction end dysfunction. It is yet another feature of this invention that cataract 3~ formation secondary to surgical trauma and/or short and long erm inflammation may be minimized and/or avoided.
Tt is yet another advantage of this invention that flare, white cells, vitreous reaction, cystoid macular edema, hyopyon, uveitis, and secondary glaucoma typically associated by those skilled in the art with W~ 93/03776 -6- PL'fIUS92/06~18 the use of anterior chamber eys implants may be avoided.
Tt is another object of this invention to provide a method of preparing the above-described minus power anterior chamber ocular implant, wherein the implant avoids the above-discussed problems when it is surgically implanted into the eye, and may subsea~uently be removed from the eye if necessary.
Tt is one feature of the method of preparing such an implant that the coating may be banded covalently, by ionic attraction, or hydrogen bonding to the surface of the implant. It is another feature of this method that the sulfated polysaccharide coating may be selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate,:dermatan sulfate, chitosan sulfa e, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid. It is yet another feature of this method that the coating may be additionally complexed with compounds having anticoagulation ~0 properties; such as antithrombin. It is yet another feature of this method that the coating may additionally comprise onie or more compounds capable of absorbing ultravzole~ and other short wavelength -radiation. Tt is yet another feature of this method that plasma-treating may ffirst be used to treat an uncoated implant~and the medicament may thereafter be bonded' to the plasma-treated surface.
It is ~ne advantage of this method that it avoids attraction and minimizes the adherence of white blood cells, pigment granules and intraocular tissue to its surface. It is another. advantage of this method that it avoids stimulation of white cell activity and enzyme release which results-in corneal endothelial destruction and dysfunction. It is yet another feature of this method that cataract formatian secondary to surgical trauma andjor short and fang term inflammation may be minimized and/or avoided.
It is yet another object of this invention to provide a method of using the coated anterior chamber ocular implant of this invention in the treatment of l0 myopia, wherein the implant is surgically implanted in the phakic eye to compensate for refractive errors, thereby advantageously avoiding the above-described problems. The implant may subsequently be removed from the eye, if necessary.
15 Summary of the Invention This invention is directed to a minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having an anatomic lens in situ.. The implant comprises a negative artificial 20 refracting lens having at least one concave surface and a surface coating comprising a compatible sulfated polysaccharide medicament, and mean's far positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic 25 lens.
The sulfated polysaccharide is preferably selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfonated 30 hyaluronic acid, with heparin being particularly preferred. The heparin typically has a molecular weight in the range of about 2,500-15,000 daltons, preferably about 2,500-10,000 daltons, most preferably abut 2,00-5,300 daltons. uhe coating is preferably 35 bonded to the surface of the implant by means of ionic . . .. , . , , , , ., ' . : :.~ , .... -. .. . v . w. '. ', . :' ., .. . .
W~ ~3/03~77 _~- PCT/US92/06R.~8 2~.15~~~
attraction, hydrogen bonding, or covalent banding with covalent bonding being particularly preferred: The coating typically has a thickness in the range from about 1/100,OOOmm to 1/100mm, and constitutes from about 1/10,000% to about 1/10% by weight of the implant. The coating may additionally be complexed with compounds having anticoagulation properties such as antithrombin.
The coated minus power anterior chamber ocular implant of this invention is advantageous in that it may be implanted in the phakic eye to compensate for refractive errors, yet has increased biocompatibility in the anterior chamber of the eye, and thus avoids the problems typically associated with such implantation, including damage to the corneal endothelium, inflammatory responses in the anterior or posterior segments of the eye, particularly the formation of cataracts ~.n the natural lens which is left in situ vwhen the refractive anterior chamber~implant is placed 0 in the eye.
This invention i~ further directed to the method of preparing such a c~ated minus power anterior chamber ocular imglant, themethod comprising the steps of first exposing an uncoated surface of the implant to a ~lasrna to generate a plasma-treated implant having a surface having constituents selected from the group consisting of amines, carboxylic acids, active free radicals, and passive free radicals, and thereafter bonding the sulfated polysaccharide medicament to the plasma-treated implant surface.
This invention is,also directed to a method of treating myopia comprising surgically implanting and anchoring in the anterior chamber of a phakic eye the coated minus power anterior chamber ocular implant of this invention.
..7 .r... " ..:.r 5 ... ~:.~ . . .. ' ...y t ; :;~ V ..:.,, .:.; , ,.:. . :::
. '.~ .:' ., r'. 7 . .. , '. . .. '... : : ' '.. ' ;., ' ,: . . ., : '. ' .,' . ' '.
., 5;~ r .... ,." . .~::.. . . . :1.: ;., ....~~. .~ ~ .....:...., .,......
.~. . ,.: . . .. '..:,.. ~ ........~...,'.. ..,..,;:.. . ,~.....~..
.....:n ... ... .,... .W..~... ...(...,~y n.... .:'.... ..:. ~_;.y ,:~,...,~~
....'. .,... .,.,.;.y. ..,..... : . ... .- .. ....
. . ... . v.... ( ? ! . , . . . . .'. ' ...
~,~ W~ 13103776 ~ 1 ~ ~ ~ ~ PCTIUS92/06~18 _g_ . ~
Erief Description of the Drawings The anterior chamber ocular implant of the present invention will hereinafter be described with reference, in part, to the accompanying drawings, in which:
Figure 2 is top plan view of one embodiment of an anterior chamber ocular implant in accordance with the present invention, wherein the negative refracting lens is biconcave.
Figure 2 is a side cross-sectional view of an eye containing the biconcave implanted anterior chamber ocular implant of Figure 1.
Description of the Preferred Embodiments This invention is directed to a minus power anterior chamber ocular implant for placement in tha anterior craamber of an eye having an anatomic lens in situ. As used ire this description and in the appended claims, the term 'minus power anterior chamber ocular implant' refers specifically to a negative refracting lens,surgically implanted in the phakic eye to compensate for and/or correct refractive errors, and specifically excludes intraocular lenses which are surgically inserted in the aphakic eye, such as are disclosed, for example, in U.S. Pat. No. 4,240,163 (Galin) The negative refracting lens employed in the present invention his a lens shape with two refractive surfaces, at least ane of which is concave, such that the combined refractive powers of the two surfaces is a minus or negative.' Such lenses are typically employed to correct high myopia.
As discussed hereinabove, uncoated minus power anterior chamlber ocular implants are well known to those skilled in the art: The optical portion of the implant employed in the present invention is preferably fabricated from compounds such as polymethyl -1~°
methacrylate, poly-2- hydroxyethyl methacrylate, methyl methacrylate copolymers, siloxanylalkyl, fluoroalkyl and aryl methacrylates, silicone, silicone elastomers, polysulfones, polyvinyl alcohols, polyethylene oxides, copolymers of fluoroacrylates and methacrylates, and polymers and copolymers of hydroxyalkyl methacrylates, such as 2-hydroxyethyl methacrylate, glyceryl methacrylate, 2-hydroxypropyl methacrylate, as well as methacrylic acid, acrylic acid, acrylamide methacrylamide, N,N-dimethylacrylamide, and N-vinylpyrrolidone. Additionally, compounds which absorb ultraviolet or other short wavelength (e. g.
below about 400 nm) radiation, such as compounds derived from benzotriazole groups, benzophenone groups, or mixtures thereof may be added to the monomers and/or polymers which constitute the anterior chamber ocular implant. Other compounds well known to those skilled in the art may also be used in fabricating the anterior chamber ocular implant employed in this invention.
It is well known to these skilled in the art that when positioning an implant within the anterior chamber of the phakic eye, it is important to avoid, inter alia, contact between the implant and the anatomic lens residing in the posterior chamber. In the present invention, haptics are integral to the optical portion of the implant, and position or "vault"
the artificial lens in the anterior chamber of the eye to prevent such contact. The haptic;s may be of the same material as described above for the optical por-tion of the implant, or may be made of materials such as polypropylene. Haptics which may be employed in the implant of the present invention include haptirs such as disclosed in U.S. Patent No. 4,676,792 (Praeger), Most minus power anterior chamber implants typi-cally have an overall diameter of approximately 12-14 ,;., .
f..:
. , ...
,,:
4'4':~~A' ~ .'.~~I':;
.. S.-.'.
,..>~f"
,.:y.;.,: .
Y '. r l y.x, .'J I ~.. .1;. ~' n .
f ': ~ h J I,.'..'S '..
.1:L ... .. h . . f.. v. . ..h h v.. ...Y ".
.1.~~~. I i:
J .- ,.f ,I a.. ..A. '..i.,~~.:
a f ., . . ...a.:a...
..L .~, s ~,-1-.:,.i ' e.
. I'.;~; t. ..
,,.v.,n . ':..i a. a >~a , ,. . ~c. .:a;, ..
. .. r r' ... ...5 :.
y, , i :~. ~, ...r .
..k.. . .~.. Y. :'A .;
I v . .''Y.
, . r . ,. . ':...': y . ,. i .:rr. ., . r,r .,.....
, . . ,.. a,.: r, ., ~.
. . ,, ~. 's' ,., .. . . . ;:, .'x m ,..3...':, .. .... .... . .,... . .. .,. r..', ..
..".....,.... ..,.... ......... .......:~~...., ;.r....
~.~, !V6'0 93/03776 -12 - ~ ~ ~ ~ ~ ~ ~ PCT/iJS92/1~6818 mm, if in a single piece of silicone or plastic, with an optical diameter of 4-6 mm. The center thickness and posterior radii of the optical portion of the implant typically varies according to the power desired and the material used. Such implants may typically weigh up to 25 mg in air, or about 0.5-4 mg in aqueous medium. Examples of uncoated anterior chamber ocular implants commercially a~railable include those available from, for example, Domilens, Tnc. of Lyon, France.
The sulfated polysaccharide medicament coating employed in conjunction with the anterior chamber ocular implant in this invention is preferably selected from the group cansisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate; chitosan sul-fate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid. Heparin is particularly preferred for use as the coating, with heparin having a molecular weight in the range of about 2,500-15,000 daltons.
Commercially available heparin, which usually has a molectalar weight of from about 12,000 to about 15,000 daltons; may lead to platelet agglutination.
Consequently, lower molecular weight heparin (a derivative or fraction) may be more suitable in the °
range of mo7:ecular weight of from about 2,500-10,000, '25 most preferabl~r about 2,500-5,300 daltons and even somewhat'higher. These low molecular weight heparins can be prepared by enzymatic hydrolysis or depolym~rization of heparin with heparinase as disclosed, for example, by U:S. Pat. ~Jo. 3,766,1E7 (Lasker ~t al.)~ ~r by depolymerizing either heparin residues or commercial porcine or bovine heparin by reacting the heparin material with a blend of ascorbic acid anal hydrogen peroxide, the reaction products then being isolated and fractionated by precipitation using an organic solvent, such as ethanol, methanol, acetone, or methyl ethyl ketone. Commercially available heparin Yrt4.y .:..,....,~: :".,... ~ v.-,:',.' 6 ,-.:~... ;..., ,.,.,::f'.:.; ':".':
'..":'. ...; ~:.':' .-;.~...'. ..-.~,'.... .~.':-.:.' .~ ..".,.: ';'.....,., ..., ..~,.~, , . .....
A,i.s !~.~)~' , s . ':.x m' !.':;'~ .;~y ." . ::. .. .,..,~.: ., ~': . '- , .~:y " . .' .,,~..,.,. ; :
; . :.,,.. .,,... , .. ; '' .~ ...,, ,.':.. . ,~~..'. ... . ,:;.., ~~yt.';. ; ~ ~ , ,f~, . . ' : 5 .
YAy m.
1 .
;.y. 1 W ~~.. , ~Y .~...
. ..~ ø j ;' t:
I
't ..
r.'71r ..1.
>9 L n '. .,.:~.',.,.,..,...,. , .:", ;r,:.,.: , . ~:~; ,.:.., , , . "'. ..,....
.sn,., :I. ..,...... . ~,:.',:. . v.~...'~ , ~:',:::. ' , '.:~ ,.;:. ,, ' -,.'~ ~,,... "'.' ;.
. l . .. !. A ..
1w. . ~ :..1..:...
~,. . . :~~ t .
WO 93103776 PCTii1S92/O(~~?~8 -12=
may also be cleaved chemically using nitrous acid to yield lower molecular weight heparin, including heparin having a molecular weight in the range of about 2500°10,000 daltons, preferably 2500-5300 daltons.
In one preferred embodiment of this invention, as depicted in Figure 1, the representative minus power anterior chamber ocular implant 2 has two haptics 4 and 6 integral to the negative artificial refracting lens 8, so that when implanted into the anterior chamber of the eye, the lens 8 is positioned to prevent contact between the implant 2 and the anatomic lens (not shown). In this view a first surface 10 of the negative refracting lens is visible, and the second surface 12 of the negative refracting lens resides directly below first surface 10. Both surfaces 10 and 12; as well as haptics 4 and 6 have a sulfated poly-saccharide medicament coating 14 (not shown).
As shown in;Figur~ 2, the implant 2 is implanted witha.n the anterior chamber l6 of the eye 18, with the negative artificialrrefracting lens 8 positioned or .vaulted by haptics 4 and G to prevent contact between the amplant 2 and the anatomic lens 20. The implant 2 is also pasitioned to avoid contacting the corneal endothelium ~2 behind the cornea 24, as well as the iris 26. In this embodiment, the first surface 10 is concave, and the second surface 12 is concave. In other embodiments of this invention, the first surface 10 may be concave, convex or planar, and the second surface 12 may be concave, convex or'planar, with the 30: proviso that at least'one of surfaces 10 or 12 is concave. The first surface 10 and second surface 12, ~s well as the haptics 4 and 6, are coated with medicament coating,~4. In Figure 2, means for anchoring or fixing the haptics 4, 6 and implant 2 in the anterior chamber of the eye are not shown. Such means are well known to those skilled in the art; for 4 . I
1, . .
7 , ~~ :: b ': J ' 7 ~ p..~.
~'~rrw .I y a 9...
. i..
;b. ..
7.P
..n, n . .
.. ... ... . t.,... . ,.. v. .. .
. ,. m............. t .... n ...,. 4~. ,i.~7 t. ... . .
.,. . ... ,. ,r.. .... . f. I..~.. .(....m.. ,..v...m p.. ~:..t.. ."a:.. 5: .
..
f"~IaVO 93/03776 ~ C~ ~ ~ ~ P~.°f/US32f06818 _13_ example, the footplates disclosed' in U.S. Patent Rlo. 4,f7f,792 (Praeger) may be employed in the present invention.
The coating of the present invention may be bonded to the surface of the implant by any method of bonding well known by those skilled in the art, preferably in such a manner that the coating is bonded to the surface of the implant by means of covalent bonding, ionic attraction, or hydrogen bonding, with covalent bonding being particularly preferred. In one particularly preferred embodiment of this invention, heparin is covalently bonded to the surface of the implant by means of an end-groug attachment of heparin to the implant surf ace.
Iz~ anather particularly preferred embodiment, the implant surface is first treated with a plasma to generate an amine-c~ntaining surface, a carboxylic acid containing-surface,'or an active or passive free radical-containing surface, and heparin compounds or derivatives thexeof .is hereafter employed to coat the implant'surface: In one emb~diment; plasma treating is . accomp7:ished by setting the implant in a gaseous atmosphere such as an oxygen rarefied atmosphere, and subjec~,ing he implant to ari eleci~rmmagnetic field for a given period of time. For example; in one embodiment the implant my be subjected from 1-20 minutes, say 2 minutes, to an electromagnetic field having a frequency in the range of 1-50 MHz, say about 10-15 MHz,~~with a corresponding power range of 10-500 W/cm2, say about 100 W/cm2e In another emlaodiment; in accordance with tech-niques well known to these skilled in the art, plasma treating is accomplished by applying a voltage between electrodes wherein the uncoated implant resides between the electrodes in the presence of a gas, thereby caus--ing a highly ionized gas to bombard the implant surface so as to cause the desired constituent (i.e. amine, carboxylic acid, active free radical, or passive free radical) to reside in the implant surface. The gas employed may comprise a carrier gas, either alone or in combination with other gases. The carrier gas may be any gas, but argon or air are preferred, with argon gas typically being used. The pressure of the gas is typically between 1.0 and 3,000 torn. Equipment which may be employed to achieve such plasma treating is well known to those skilled in the art, such as the equip-ment described in U.S. Patent No. 4,780,176 (Sudarshan et al.) for plasma cleaning and etching a metal sub-strate .
In the present invention, a power input to the electrode of 10-500W may be employed to achieve a corresponding potential difference across the gap between the electrodes.
To generate an amine-containing surface, a plasma containing ammonia or a primary amine-containing material is used. A carboxylic acid-containing surface is generated by an oxidative reaction occurring at the surface or by having residual water in the plasma under inert conditions. In such an embodiment, argon is typically used as the carrier gas. Exposing the surface to argon gas plasma at sufficiently high power causes bond fission, yielding an active free radical-containing surface, whereas exposing the surface to oxygen or air plasma under oxidizing conditions results in a passive free radical-containing surface.
The method of coating the medicament-coated implant of this invention may be any appropriate well known coating technique, such as immersion coating, spray coating and the like, using a suitable solution or dispersion of the medicament dissaived or dispersed in an appropriate solvent ur dispersant, such as water, ethanol, and the like, with the solvent not affecting 22~56~~.
,,,,~. WO 93!03776 -15- ~ PCT/US92/06818 the optics of the lens material. 'The coating solution or dispersion has a conventionah concentration of medicament which corresponds to the particular coating particularly advantageous in eyes which have had antecedent inflammation.
Moreover, it is theorized that the specified coating alters the abrasive potential of the implant and reduces the trauma associated with insertion and maintenance thereof. In addition, the specified coating may reduce the inflammatory potential of the implant and the dangerous sequelae .resulting therefrom, including, among other effects, cataract formation.
The coated implant may also act as a therapeutic agent to prevent and treat the untoward rteactions to the implant previously described.
The following examples illustrate preferred embodiments of the implant of this invention. It will be understood that the following examples are merely illustrative, and are' not meant to ).imit the invention in any way.
Example 1 An uncoated minus power anterior chamber ocular implant in accordance with this invention and containing surface carboxyl groups is surface coated with low molecular weight heparin (i.e. about 2,500-5,300 daltons) by the following procedure. The carboxyl group-containing surface of the implant may preferably be made by initially incorporating about 5 weight per cent methacrylic acid into the monomer formulation used in preparing the implant.
Alternatively, surface hydrolysis of pendant acrylate or methacrylate groups residing on the surface of the implant may be employed. in a manner well known to those skilled in thA art. The pendant carboxylic acid groups on the surface of the implant are then reacted with a commercially available diamine, such as hexamethylene diamine or a polymeric diamine such as those commercially available under the JEFFAMINE~series WO 93f03776 - PCT/US~2106518 -1?
trade name fxom Texaco Chemical Company, in the pres-ence of a water-soluble carbodimide coupling agent, to generate an amine grafted surface (through amide bond formation) where the non-attached portion of the amine resides as a free primary amine. To the free primary amine grafted surface is added the low molecular weight heparin that contains a terminal aldehyde group, and the aldehyde group is then coupled with the primary amine on the surface of the implant by a water-soluble 0 carbodimide to yield a Schiff base, which is then reduced o give a.secondary amine linkage to which is attached the ~,ow molecular weight heparin.
Exam~Ie 2 In another'preferred embodiment, an undated minus power anterior chamber ocular implant in accordance with this invention and: containing surface carboxyl groups; is obtained ,in accordance with Example 1.
However; instead'of reacting the surface carboxylic groups with a d.iamine, as in Example 1, an aldehyde-24 terminated-heparin is first coupled with a diamine.
This reaction utilizes an excess of diamine, such as a low molecular weight; water-soluble diamine, that °
reacts with the aldehyde-terminated heparin through one of its amine groups, generating an amido-bonded heparin derivatized with a free, pendant amino group. This water-soluble compouhd is then, purified by dialysis to eliminate the excess, unreacted diamine, and the product obtain~c~ by lyophilization. 'The aminated heparin is hen reacted with the hydrolyzed surface of the anterior chamber ocular implant through its surface carboxyl groups in the presence of a water-soluble carbodiimide coupling agent. In contrast to the previously described embodiment of Example 1, this process involves only one coupling reaction on the surface of the implant rather than two.
< <.
. I ~:.~:' , ..- ,.::...: :":,.';:. .":", .~....,,.,,;..r~.,;;,~ .....:'~..
.....,:._ ,...; ..~ ,:..:... ... ,;..;.... :~::.,.'..,::'.........
'..'.,.,.;..., ., ..
::~". _.
'.1AY. : .
r~
~~-P ..
n f .
n ,~r :ri a r '. . . ~: . f. "
~ ~ .. t.~
! x' K o f . .
s~ .. , r t ...1 ., r ...
. ".f .,.;.... . . ~,.,, ;., .., ,.;..:..!.... . v';.~. . . ,;~,v~. ~'~.-:~ .
. ~'~. ,...,..:.;- .'.'.',:.v.. .....,,...;., :.. ~ ..,..~;:.:. ,.. .. .~r; .
~,~:' . ~ ~:.u " . ,:,;,-:.,v .,..., WO 93/03776 _ _ PCT/US92/06R18 2~.~.~~~~. ~8 Example 3 In yet another preferred embodiment, an uncoated minus power anterior chamber ocular implant in accord-ante with this invention is treated with a plasma in accordance with methods as previously described to generate an amine-containing surface, a carboxylic acid-containing surface, or an active or passive free radical-containing surface. If an amine-containing surface is obtained, aldehyde-terminated heparin may be employed to coat the surface of the implant in accordance with Example 1. If a carboxylic acid-containing surface d s obtained, aminated heparin may be employed to coat the surface of the implant in accordance with Example 2. If an active or passive free radical-containing surface is obtained, amine or Garb~xylic acid-containing compounds of low or high molecular weight may be reacted with the surface to yield a covalently attached amine or carboxylic acid-containing implant surface, respectively, to which the designated aldehyde-terminated or aminated heparin compounds set forth in Examples 1 and 2, respectively, are employed to Goat the surface of the implant with heparin. In a particularly preferred embodiment, the plasma treatment employed will act in such a manner as v25 to permit trace surface moisture residing in the uncoated implant-to be converted into passive free radical'coupling agents via the formation of peroxide groups.
Wli.th respect to the foregoing examples, if anti-coagulat'~on propert~:es are desired or wish to be increased, ~antithrombin maybe added to complex with binding sites on the heparinized surface. Similarly, if additional ultraviolet radiation absorbing properties are desired, compounds having ultraviolet radiation absorbing properties such as compounds having benzotriaz'ole groups; benzophenone groups, and mixtures y .:.,.
.. .
..
~,.rr".., . r.,~-, :.,h..
,,..:1..
7 .A
r .1:.
:.
rr :, "
x.1 .-u,.. r..,, t~ ..l r..
u,,... z.
I V
... I t '.,.. .1. . . , velle. . S...f.~i' ..5.,.
h .1.:
t'1 S
:r..d..A , 1 r.,'~.Iv _ . .. . < ~f .'.'7 f t ..
t . . . If , W ' 14 .. , ,.~.t , 1 . , .. , 1 . w ..
w..... .r......m,.r. .... .........................._... . F.. ._.. , . , ...
... . ~... , . . . . ... . .. ... , . .
,~.",~. W~ 93/03776 -19- ~ PCT/U~92/06818 thereof may be added into the monomer mixture to yield the minus power anterior chamber ocular implant to be coated with a compatible sulfated polysaccharide medicament in accordance with this invention.
.. S.-.'.
,..>~f"
,.:y.;.,: .
Y '. r l y.x, .'J I ~.. .1;. ~' n .
f ': ~ h J I,.'..'S '..
.1:L ... .. h . . f.. v. . ..h h v.. ...Y ".
.1.~~~. I i:
J .- ,.f ,I a.. ..A. '..i.,~~.:
a f ., . . ...a.:a...
..L .~, s ~,-1-.:,.i ' e.
. I'.;~; t. ..
,,.v.,n . ':..i a. a >~a , ,. . ~c. .:a;, ..
. .. r r' ... ...5 :.
y, , i :~. ~, ...r .
..k.. . .~.. Y. :'A .;
I v . .''Y.
, . r . ,. . ':...': y . ,. i .:rr. ., . r,r .,.....
, . . ,.. a,.: r, ., ~.
. . ,, ~. 's' ,., .. . . . ;:, .'x m ,..3...':, .. .... .... . .,... . .. .,. r..', ..
..".....,.... ..,.... ......... .......:~~...., ;.r....
~.~, !V6'0 93/03776 -12 - ~ ~ ~ ~ ~ ~ ~ PCT/iJS92/1~6818 mm, if in a single piece of silicone or plastic, with an optical diameter of 4-6 mm. The center thickness and posterior radii of the optical portion of the implant typically varies according to the power desired and the material used. Such implants may typically weigh up to 25 mg in air, or about 0.5-4 mg in aqueous medium. Examples of uncoated anterior chamber ocular implants commercially a~railable include those available from, for example, Domilens, Tnc. of Lyon, France.
The sulfated polysaccharide medicament coating employed in conjunction with the anterior chamber ocular implant in this invention is preferably selected from the group cansisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate; chitosan sul-fate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid. Heparin is particularly preferred for use as the coating, with heparin having a molecular weight in the range of about 2,500-15,000 daltons.
Commercially available heparin, which usually has a molectalar weight of from about 12,000 to about 15,000 daltons; may lead to platelet agglutination.
Consequently, lower molecular weight heparin (a derivative or fraction) may be more suitable in the °
range of mo7:ecular weight of from about 2,500-10,000, '25 most preferabl~r about 2,500-5,300 daltons and even somewhat'higher. These low molecular weight heparins can be prepared by enzymatic hydrolysis or depolym~rization of heparin with heparinase as disclosed, for example, by U:S. Pat. ~Jo. 3,766,1E7 (Lasker ~t al.)~ ~r by depolymerizing either heparin residues or commercial porcine or bovine heparin by reacting the heparin material with a blend of ascorbic acid anal hydrogen peroxide, the reaction products then being isolated and fractionated by precipitation using an organic solvent, such as ethanol, methanol, acetone, or methyl ethyl ketone. Commercially available heparin Yrt4.y .:..,....,~: :".,... ~ v.-,:',.' 6 ,-.:~... ;..., ,.,.,::f'.:.; ':".':
'..":'. ...; ~:.':' .-;.~...'. ..-.~,'.... .~.':-.:.' .~ ..".,.: ';'.....,., ..., ..~,.~, , . .....
A,i.s !~.~)~' , s . ':.x m' !.':;'~ .;~y ." . ::. .. .,..,~.: ., ~': . '- , .~:y " . .' .,,~..,.,. ; :
; . :.,,.. .,,... , .. ; '' .~ ...,, ,.':.. . ,~~..'. ... . ,:;.., ~~yt.';. ; ~ ~ , ,f~, . . ' : 5 .
YAy m.
1 .
;.y. 1 W ~~.. , ~Y .~...
. ..~ ø j ;' t:
I
't ..
r.'71r ..1.
>9 L n '. .,.:~.',.,.,..,...,. , .:", ;r,:.,.: , . ~:~; ,.:.., , , . "'. ..,....
.sn,., :I. ..,...... . ~,:.',:. . v.~...'~ , ~:',:::. ' , '.:~ ,.;:. ,, ' -,.'~ ~,,... "'.' ;.
. l . .. !. A ..
1w. . ~ :..1..:...
~,. . . :~~ t .
WO 93103776 PCTii1S92/O(~~?~8 -12=
may also be cleaved chemically using nitrous acid to yield lower molecular weight heparin, including heparin having a molecular weight in the range of about 2500°10,000 daltons, preferably 2500-5300 daltons.
In one preferred embodiment of this invention, as depicted in Figure 1, the representative minus power anterior chamber ocular implant 2 has two haptics 4 and 6 integral to the negative artificial refracting lens 8, so that when implanted into the anterior chamber of the eye, the lens 8 is positioned to prevent contact between the implant 2 and the anatomic lens (not shown). In this view a first surface 10 of the negative refracting lens is visible, and the second surface 12 of the negative refracting lens resides directly below first surface 10. Both surfaces 10 and 12; as well as haptics 4 and 6 have a sulfated poly-saccharide medicament coating 14 (not shown).
As shown in;Figur~ 2, the implant 2 is implanted witha.n the anterior chamber l6 of the eye 18, with the negative artificialrrefracting lens 8 positioned or .vaulted by haptics 4 and G to prevent contact between the amplant 2 and the anatomic lens 20. The implant 2 is also pasitioned to avoid contacting the corneal endothelium ~2 behind the cornea 24, as well as the iris 26. In this embodiment, the first surface 10 is concave, and the second surface 12 is concave. In other embodiments of this invention, the first surface 10 may be concave, convex or planar, and the second surface 12 may be concave, convex or'planar, with the 30: proviso that at least'one of surfaces 10 or 12 is concave. The first surface 10 and second surface 12, ~s well as the haptics 4 and 6, are coated with medicament coating,~4. In Figure 2, means for anchoring or fixing the haptics 4, 6 and implant 2 in the anterior chamber of the eye are not shown. Such means are well known to those skilled in the art; for 4 . I
1, . .
7 , ~~ :: b ': J ' 7 ~ p..~.
~'~rrw .I y a 9...
. i..
;b. ..
7.P
..n, n . .
.. ... ... . t.,... . ,.. v. .. .
. ,. m............. t .... n ...,. 4~. ,i.~7 t. ... . .
.,. . ... ,. ,r.. .... . f. I..~.. .(....m.. ,..v...m p.. ~:..t.. ."a:.. 5: .
..
f"~IaVO 93/03776 ~ C~ ~ ~ ~ P~.°f/US32f06818 _13_ example, the footplates disclosed' in U.S. Patent Rlo. 4,f7f,792 (Praeger) may be employed in the present invention.
The coating of the present invention may be bonded to the surface of the implant by any method of bonding well known by those skilled in the art, preferably in such a manner that the coating is bonded to the surface of the implant by means of covalent bonding, ionic attraction, or hydrogen bonding, with covalent bonding being particularly preferred. In one particularly preferred embodiment of this invention, heparin is covalently bonded to the surface of the implant by means of an end-groug attachment of heparin to the implant surf ace.
Iz~ anather particularly preferred embodiment, the implant surface is first treated with a plasma to generate an amine-c~ntaining surface, a carboxylic acid containing-surface,'or an active or passive free radical-containing surface, and heparin compounds or derivatives thexeof .is hereafter employed to coat the implant'surface: In one emb~diment; plasma treating is . accomp7:ished by setting the implant in a gaseous atmosphere such as an oxygen rarefied atmosphere, and subjec~,ing he implant to ari eleci~rmmagnetic field for a given period of time. For example; in one embodiment the implant my be subjected from 1-20 minutes, say 2 minutes, to an electromagnetic field having a frequency in the range of 1-50 MHz, say about 10-15 MHz,~~with a corresponding power range of 10-500 W/cm2, say about 100 W/cm2e In another emlaodiment; in accordance with tech-niques well known to these skilled in the art, plasma treating is accomplished by applying a voltage between electrodes wherein the uncoated implant resides between the electrodes in the presence of a gas, thereby caus--ing a highly ionized gas to bombard the implant surface so as to cause the desired constituent (i.e. amine, carboxylic acid, active free radical, or passive free radical) to reside in the implant surface. The gas employed may comprise a carrier gas, either alone or in combination with other gases. The carrier gas may be any gas, but argon or air are preferred, with argon gas typically being used. The pressure of the gas is typically between 1.0 and 3,000 torn. Equipment which may be employed to achieve such plasma treating is well known to those skilled in the art, such as the equip-ment described in U.S. Patent No. 4,780,176 (Sudarshan et al.) for plasma cleaning and etching a metal sub-strate .
In the present invention, a power input to the electrode of 10-500W may be employed to achieve a corresponding potential difference across the gap between the electrodes.
To generate an amine-containing surface, a plasma containing ammonia or a primary amine-containing material is used. A carboxylic acid-containing surface is generated by an oxidative reaction occurring at the surface or by having residual water in the plasma under inert conditions. In such an embodiment, argon is typically used as the carrier gas. Exposing the surface to argon gas plasma at sufficiently high power causes bond fission, yielding an active free radical-containing surface, whereas exposing the surface to oxygen or air plasma under oxidizing conditions results in a passive free radical-containing surface.
The method of coating the medicament-coated implant of this invention may be any appropriate well known coating technique, such as immersion coating, spray coating and the like, using a suitable solution or dispersion of the medicament dissaived or dispersed in an appropriate solvent ur dispersant, such as water, ethanol, and the like, with the solvent not affecting 22~56~~.
,,,,~. WO 93!03776 -15- ~ PCT/US92/06818 the optics of the lens material. 'The coating solution or dispersion has a conventionah concentration of medicament which corresponds to the particular coating particularly advantageous in eyes which have had antecedent inflammation.
Moreover, it is theorized that the specified coating alters the abrasive potential of the implant and reduces the trauma associated with insertion and maintenance thereof. In addition, the specified coating may reduce the inflammatory potential of the implant and the dangerous sequelae .resulting therefrom, including, among other effects, cataract formation.
The coated implant may also act as a therapeutic agent to prevent and treat the untoward rteactions to the implant previously described.
The following examples illustrate preferred embodiments of the implant of this invention. It will be understood that the following examples are merely illustrative, and are' not meant to ).imit the invention in any way.
Example 1 An uncoated minus power anterior chamber ocular implant in accordance with this invention and containing surface carboxyl groups is surface coated with low molecular weight heparin (i.e. about 2,500-5,300 daltons) by the following procedure. The carboxyl group-containing surface of the implant may preferably be made by initially incorporating about 5 weight per cent methacrylic acid into the monomer formulation used in preparing the implant.
Alternatively, surface hydrolysis of pendant acrylate or methacrylate groups residing on the surface of the implant may be employed. in a manner well known to those skilled in thA art. The pendant carboxylic acid groups on the surface of the implant are then reacted with a commercially available diamine, such as hexamethylene diamine or a polymeric diamine such as those commercially available under the JEFFAMINE~series WO 93f03776 - PCT/US~2106518 -1?
trade name fxom Texaco Chemical Company, in the pres-ence of a water-soluble carbodimide coupling agent, to generate an amine grafted surface (through amide bond formation) where the non-attached portion of the amine resides as a free primary amine. To the free primary amine grafted surface is added the low molecular weight heparin that contains a terminal aldehyde group, and the aldehyde group is then coupled with the primary amine on the surface of the implant by a water-soluble 0 carbodimide to yield a Schiff base, which is then reduced o give a.secondary amine linkage to which is attached the ~,ow molecular weight heparin.
Exam~Ie 2 In another'preferred embodiment, an undated minus power anterior chamber ocular implant in accordance with this invention and: containing surface carboxyl groups; is obtained ,in accordance with Example 1.
However; instead'of reacting the surface carboxylic groups with a d.iamine, as in Example 1, an aldehyde-24 terminated-heparin is first coupled with a diamine.
This reaction utilizes an excess of diamine, such as a low molecular weight; water-soluble diamine, that °
reacts with the aldehyde-terminated heparin through one of its amine groups, generating an amido-bonded heparin derivatized with a free, pendant amino group. This water-soluble compouhd is then, purified by dialysis to eliminate the excess, unreacted diamine, and the product obtain~c~ by lyophilization. 'The aminated heparin is hen reacted with the hydrolyzed surface of the anterior chamber ocular implant through its surface carboxyl groups in the presence of a water-soluble carbodiimide coupling agent. In contrast to the previously described embodiment of Example 1, this process involves only one coupling reaction on the surface of the implant rather than two.
< <.
. I ~:.~:' , ..- ,.::...: :":,.';:. .":", .~....,,.,,;..r~.,;;,~ .....:'~..
.....,:._ ,...; ..~ ,:..:... ... ,;..;.... :~::.,.'..,::'.........
'..'.,.,.;..., ., ..
::~". _.
'.1AY. : .
r~
~~-P ..
n f .
n ,~r :ri a r '. . . ~: . f. "
~ ~ .. t.~
! x' K o f . .
s~ .. , r t ...1 ., r ...
. ".f .,.;.... . . ~,.,, ;., .., ,.;..:..!.... . v';.~. . . ,;~,v~. ~'~.-:~ .
. ~'~. ,...,..:.;- .'.'.',:.v.. .....,,...;., :.. ~ ..,..~;:.:. ,.. .. .~r; .
~,~:' . ~ ~:.u " . ,:,;,-:.,v .,..., WO 93/03776 _ _ PCT/US92/06R18 2~.~.~~~~. ~8 Example 3 In yet another preferred embodiment, an uncoated minus power anterior chamber ocular implant in accord-ante with this invention is treated with a plasma in accordance with methods as previously described to generate an amine-containing surface, a carboxylic acid-containing surface, or an active or passive free radical-containing surface. If an amine-containing surface is obtained, aldehyde-terminated heparin may be employed to coat the surface of the implant in accordance with Example 1. If a carboxylic acid-containing surface d s obtained, aminated heparin may be employed to coat the surface of the implant in accordance with Example 2. If an active or passive free radical-containing surface is obtained, amine or Garb~xylic acid-containing compounds of low or high molecular weight may be reacted with the surface to yield a covalently attached amine or carboxylic acid-containing implant surface, respectively, to which the designated aldehyde-terminated or aminated heparin compounds set forth in Examples 1 and 2, respectively, are employed to Goat the surface of the implant with heparin. In a particularly preferred embodiment, the plasma treatment employed will act in such a manner as v25 to permit trace surface moisture residing in the uncoated implant-to be converted into passive free radical'coupling agents via the formation of peroxide groups.
Wli.th respect to the foregoing examples, if anti-coagulat'~on propert~:es are desired or wish to be increased, ~antithrombin maybe added to complex with binding sites on the heparinized surface. Similarly, if additional ultraviolet radiation absorbing properties are desired, compounds having ultraviolet radiation absorbing properties such as compounds having benzotriaz'ole groups; benzophenone groups, and mixtures y .:.,.
.. .
..
~,.rr".., . r.,~-, :.,h..
,,..:1..
7 .A
r .1:.
:.
rr :, "
x.1 .-u,.. r..,, t~ ..l r..
u,,... z.
I V
... I t '.,.. .1. . . , velle. . S...f.~i' ..5.,.
h .1.:
t'1 S
:r..d..A , 1 r.,'~.Iv _ . .. . < ~f .'.'7 f t ..
t . . . If , W ' 14 .. , ,.~.t , 1 . , .. , 1 . w ..
w..... .r......m,.r. .... .........................._... . F.. ._.. , . , ...
... . ~... , . . . . ... . .. ... , . .
,~.",~. W~ 93/03776 -19- ~ PCT/U~92/06818 thereof may be added into the monomer mixture to yield the minus power anterior chamber ocular implant to be coated with a compatible sulfated polysaccharide medicament in accordance with this invention.
5 This invention is also directed to a method of treating myopia comprising surgically implanting and anchoring in an anterior chamber of a phakic eye a minus power lens comprising at least one concave surface and a surface coating comprising a compatible sulfated polysaccharide medicament.
Again, while not wishing to be bound by any one theory; it is theorized that the present invention, wherein the coating is bonded to the implant surface as described herein, is advantageous over intraocular lenses'which employ covalent attachment of heparin to a polyamine that is ionically adsorbed onto the lens surface, in that the coating of the present invention ~a less likely to be released and dissipated in the aqueous humor of tk~e anterior and posterior chambers of the eye.
Although this invent~.on has been illustrated by reference o specific embodiments, it will be apparent to those skilled in the art that carious changes anc'~
modifications may be fade which clearly fall within the scope o~ this invention.
Again, while not wishing to be bound by any one theory; it is theorized that the present invention, wherein the coating is bonded to the implant surface as described herein, is advantageous over intraocular lenses'which employ covalent attachment of heparin to a polyamine that is ionically adsorbed onto the lens surface, in that the coating of the present invention ~a less likely to be released and dissipated in the aqueous humor of tk~e anterior and posterior chambers of the eye.
Although this invent~.on has been illustrated by reference o specific embodiments, it will be apparent to those skilled in the art that carious changes anc'~
modifications may be fade which clearly fall within the scope o~ this invention.
Claims (26)
1. ~A minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having~
an anatomic lens in situ, comprising a negative artificial refracting lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic lens.
an anatomic lens in situ, comprising a negative artificial refracting lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic lens.
2.~The implant according to Claim 1, in which the sulfated polysaccharide is selected from the group consisting of heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid.
3. ~The implant according to Claim 2, in which the sulfated polysaccharide is heparin having a molecular weight in the range of about 2,500-15,000 daltons.
4.~The implant according to Claim 3, in which the heparin has a molecular weight in the range of about 2,500-10,000 daltons.
5. ~The implant according to Claim 4, in which the heparin has a molecular weight in the range of about 2,500-5,300 daltons.
6. ~The implant according to Claim 1, in which the coating is covalently bonded to the surface of the implant.
7. The implant according to Claim 1, in which the coating is bonded by ionic attraction to the surface of the implant.
8. The implant according to Claim 1, in which the coating is bonded by hydrogen bonding to the surface of the implant.
9. The implant according to Claim 6, in which heparin is covalently bonded to the surface of the implant by means of an end-group attachment of heparin to the implant surface.
10. The implant according to Claim 1, in which the coating has a thickness in the range of from about 1/100,000mm to 1/100mm.
11. The implant according to Claim 1, in which the coating constitutes from about 1/10,000% to about 1/10% by weight of the implant.
12. The implant according to Claim 1, in which the coating additionally comprises at least one compound having anticoagulation properties.
13. The implant according to Claim 12, in which the coating is additionally complexed with antithrombin.
14. The implant according to Claim 1, in which the implant additionally comprises at least one compound capable of absorbing ultraviolet radiation.
15. The implant according. to Claim 14, in which the ultraviolet radiation absorbing compounds are selected from the group consisting of compounds having benzotrizole groups, benzophenone groups, and mixtures thereof.
16. A method of preparing a minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having an anatomic lens comprising a negative artificial refracting lens having at least one surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic lens, the method comprising the steps of first exposing an uncoated implant to a plasma to generate a plasma-treated implant having a surface with constituents selected from the group consisting of amines, carboxylic acids, active free radicals, and passive free radicals, and thereafter bonding the sulfated polysaccharide medicament to the plasma-treated implant surface.
17. The method according to Claim 16, in which the sulfated polysaccharide is heparin having a molecular weight in the range of about 2,500-15,000 daltons.
18. The method according to Claim 16, in which the plasma-treated implant has an amine-containing surface comprising primary amines.
19. The method according to Claim 18, in which heparin is bonded to the amine-containing surface by contacting the amine-containing surface with heparin containing a terminal aldehyde group, coupling the aldehyde group to the primary amines to produce a Schiff base, and thereafter reducing the Schiff base to produce a secondary amine linkage between the heparin and implant surface.
20. The method according to Claim 16, in which the plasma-treated implant has a carboxylic acid-containing surface.
21. The method according to Claim 20, in which heparin is bonded to the carboxylic acid-containing surface by first coupling an aldehyde-terminated heparin with a diamine to generate an aminated heparin, and thereafter contacting the aminated heparin with the carboxylic acid-containing surface in the presence of water-soluble carbodimide coupling agent.
22. The method according to Claim 16, in which the plasma-treated implant has an active free radical-containing surface.
23. The method according to Claim 16, in which the plasma-treated implant has a passive free radical-containing surface.
24. The method according to either Claim 22 or Claim 23, in which heparin is bonded to the free radical-containing surface by first reacting at least one compound selected from the group consisting of amine and carboxylic acid-containing compounds with the free radical-containing surface, and thereafter contacting the surface with at least one heparin compound selected from the group consisting of aldehyde-terminated and aminated heparin compounds.
25. ~The method according to Claim 16, in which surface moisture residing in the uncoated implant surface is converted by plasma exposure into passive free radical coupling agents.
26. ~Use of a minus power anterior chamber ocular implant in an anterior chamber of a phakic eye having an anatomic lens in situ, said implant comprising a negative artificial refracting lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic lens, for treating myopia.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74592791A | 1991-08-16 | 1991-08-16 | |
| US07/745,927 | 1991-08-16 | ||
| PCT/US1992/006818 WO1993003776A1 (en) | 1991-08-16 | 1992-08-13 | Medicament coated refractive anterior chamber ocular implant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2115651A1 CA2115651A1 (en) | 1993-03-04 |
| CA2115651C true CA2115651C (en) | 2003-07-08 |
Family
ID=24998820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002115651A Expired - Lifetime CA2115651C (en) | 1991-08-16 | 1992-08-13 | Medicament coated refractive anterior chamber ocular implant |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US5652014A (en) |
| EP (1) | EP0601055B1 (en) |
| JP (1) | JPH06509731A (en) |
| AT (1) | ATE193654T1 (en) |
| AU (1) | AU664858B2 (en) |
| BR (1) | BR9206365A (en) |
| CA (1) | CA2115651C (en) |
| DE (1) | DE69231155T2 (en) |
| DK (1) | DK0601055T3 (en) |
| ES (1) | ES2149178T3 (en) |
| GR (1) | GR3034339T3 (en) |
| MX (1) | MX9204726A (en) |
| SG (1) | SG81873A1 (en) |
| UA (1) | UA35578C2 (en) |
| WO (1) | WO1993003776A1 (en) |
Families Citing this family (118)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993003776A1 (en) * | 1991-08-16 | 1993-03-04 | Galin Miles A | Medicament coated refractive anterior chamber ocular implant |
| IL106922A (en) * | 1992-09-14 | 1998-08-16 | Novartis Ag | Composite materials with one or more wettable surfaces and process for their preparation |
| AU671671B2 (en) * | 1992-09-14 | 1996-09-05 | Commonwealth Scientific And Industrial Research Organisation | Multilayer materials |
| ITPD940054A1 (en) * | 1994-03-23 | 1995-09-23 | Fidia Advanced Biopolymers Srl | SULPHATED POLYSACCHARIDES |
| US5643580A (en) * | 1994-10-17 | 1997-07-01 | Surface Genesis, Inc. | Biocompatible coating, medical device using the same and methods |
| US7045585B2 (en) * | 1995-11-30 | 2006-05-16 | Hamilton Civic Hospital Research Development Inc. | Methods of coating a device using anti-thrombin heparin |
| US6562781B1 (en) | 1995-11-30 | 2003-05-13 | Hamilton Civic Hospitals Research Development Inc. | Glycosaminoglycan-antithrombin III/heparin cofactor II conjugates |
| US6491965B1 (en) * | 1995-11-30 | 2002-12-10 | Hamilton Civic Hospitals Research Development, Inc. | Medical device comprising glycosaminoglycan-antithrombin III/heparin cofactor II conjugates |
| WO1997041901A1 (en) * | 1996-05-03 | 1997-11-13 | Uros Corporation | Pentosanpolysulfate coating for medical devices |
| US5769890B1 (en) * | 1997-01-16 | 2000-09-05 | Surgical Concepts Inc | Placement of second artificial lens in eye to correct for optical defects of first artificial lens in eye |
| DE69816751T2 (en) * | 1997-05-29 | 2004-06-03 | Alcon Laboratories, Inc., Fort Worth | MATERIALS FOR TREATING THE GLAUCOMA |
| FR2773318B1 (en) * | 1998-01-08 | 2000-03-03 | Georges Baikoff | IMPLANT OF ANTERIOR CHAMBER FOR THE TREATMENT OF THE SEALED EYE |
| EP1107971B1 (en) * | 1998-08-28 | 2004-11-24 | Destiny Pharma Limited | Porphyrin derivatives, their use in photodynamic therapy and medical devices containing them |
| IT1303738B1 (en) * | 1998-11-11 | 2001-02-23 | Aquisitio S P A | CARBOXYLATE POLYSACCHARIDE CROSS-LINKING PROCESS. |
| IT1303735B1 (en) * | 1998-11-11 | 2001-02-23 | Falorni Italia Farmaceutici S | CROSS-LINKED HYALURONIC ACIDS AND THEIR MEDICAL USES. |
| US6171337B1 (en) | 1999-03-31 | 2001-01-09 | Miles A. Galin | Positive power anterior chamber ocular implant |
| US6616692B1 (en) | 1999-04-30 | 2003-09-09 | Advanced Medical Optics, Inc. | Intraocular lens combinations |
| US20060238702A1 (en) | 1999-04-30 | 2006-10-26 | Advanced Medical Optics, Inc. | Ophthalmic lens combinations |
| US20030060881A1 (en) * | 1999-04-30 | 2003-03-27 | Advanced Medical Optics, Inc. | Intraocular lens combinations |
| US6790232B1 (en) | 1999-04-30 | 2004-09-14 | Advanced Medical Optics, Inc. | Multifocal phakic intraocular lens |
| US6406494B1 (en) | 1999-04-30 | 2002-06-18 | Allergan Sales, Inc. | Moveable intraocular lens |
| US6440571B1 (en) | 1999-05-20 | 2002-08-27 | Bausch & Lomb Incorporated | Surface treatment of silicone medical devices with reactive hydrophilic polymers |
| US6630243B2 (en) | 1999-05-20 | 2003-10-07 | Bausch & Lomb Incorporated | Surface treatment of silicone hydrogel contact lenses comprising hydrophilic polymer chains attached to an intermediate carbon coating |
| JP2003503160A (en) * | 1999-06-30 | 2003-01-28 | ノバルティス アクチエンゲゼルシャフト | Ophthalmic moldings |
| US6599317B1 (en) | 1999-09-17 | 2003-07-29 | Advanced Medical Optics, Inc. | Intraocular lens with a translational zone |
| US6645246B1 (en) | 1999-09-17 | 2003-11-11 | Advanced Medical Optics, Inc. | Intraocular lens with surrounded lens zone |
| US7048759B2 (en) | 2000-02-24 | 2006-05-23 | Advanced Medical Optics, Inc. | Intraocular lenses |
| US6551354B1 (en) * | 2000-03-09 | 2003-04-22 | Advanced Medical Optics, Inc. | Accommodating intraocular lens |
| WO2001070098A2 (en) * | 2000-03-20 | 2001-09-27 | Medennium, Inc. | Method for determining the size of a posterior chamber phakic lens |
| US6599559B1 (en) * | 2000-04-03 | 2003-07-29 | Bausch & Lomb Incorporated | Renewable surface treatment of silicone medical devices with reactive hydrophilic polymers |
| US6613343B2 (en) | 2000-04-12 | 2003-09-02 | Pharmacia Groningen Bv | Injectable intraocular accommodating lens |
| US7708711B2 (en) | 2000-04-14 | 2010-05-04 | Glaukos Corporation | Ocular implant with therapeutic agents and methods thereof |
| US6638239B1 (en) | 2000-04-14 | 2003-10-28 | Glaukos Corporation | Apparatus and method for treating glaucoma |
| US6537317B1 (en) | 2000-05-03 | 2003-03-25 | Advanced Medical Optics, Inc. | Binocular lens systems |
| US6554859B1 (en) | 2000-05-03 | 2003-04-29 | Advanced Medical Optics, Inc. | Accommodating, reduced ADD power multifocal intraocular lenses |
| US6547822B1 (en) | 2000-05-03 | 2003-04-15 | Advanced Medical Optics, Inc. | Opthalmic lens systems |
| US6660035B1 (en) | 2000-08-02 | 2003-12-09 | Advanced Medical Optics, Inc. | Accommodating intraocular lens with suspension structure |
| US20030078658A1 (en) | 2001-01-25 | 2003-04-24 | Gholam-Reza Zadno-Azizi | Single-piece accomodating intraocular lens system |
| US20030078657A1 (en) * | 2001-01-25 | 2003-04-24 | Gholam-Reza Zadno-Azizi | Materials for use in accommodating intraocular lens system |
| US7780729B2 (en) | 2004-04-16 | 2010-08-24 | Visiogen, Inc. | Intraocular lens |
| US8062361B2 (en) | 2001-01-25 | 2011-11-22 | Visiogen, Inc. | Accommodating intraocular lens system with aberration-enhanced performance |
| US6858040B2 (en) * | 2001-01-25 | 2005-02-22 | Visiogen, Inc. | Hydraulic configuration for intraocular lens system |
| US20120016349A1 (en) | 2001-01-29 | 2012-01-19 | Amo Development, Llc. | Hybrid ophthalmic interface apparatus and method of interfacing a surgical laser with an eye |
| US6576012B2 (en) | 2001-03-28 | 2003-06-10 | Advanced Medical Optics, Inc. | Binocular lens systems |
| US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
| US7488303B1 (en) * | 2002-09-21 | 2009-02-10 | Glaukos Corporation | Ocular implant with anchor and multiple openings |
| US7678065B2 (en) | 2001-05-02 | 2010-03-16 | Glaukos Corporation | Implant with intraocular pressure sensor for glaucoma treatment |
| AU2002305400A1 (en) | 2001-05-03 | 2002-11-18 | Glaukos Corporation | Medical device and methods of use for glaucoma treatment |
| US6638305B2 (en) | 2001-05-15 | 2003-10-28 | Advanced Medical Optics, Inc. | Monofocal intraocular lens convertible to multifocal intraocular lens |
| US20030018382A1 (en) * | 2001-07-17 | 2003-01-23 | Pflugfelder Stephen C. | Process for improving vision |
| US20050064012A1 (en) * | 2001-07-17 | 2005-03-24 | Baylor College Of Medicine | Process for causing myopic shift in vision |
| US7763069B2 (en) | 2002-01-14 | 2010-07-27 | Abbott Medical Optics Inc. | Accommodating intraocular lens with outer support structure |
| US7186232B1 (en) | 2002-03-07 | 2007-03-06 | Glaukoa Corporation | Fluid infusion methods for glaucoma treatment |
| US7083646B2 (en) * | 2002-06-28 | 2006-08-01 | Bausch & Lomb Incorporated | Surface modification of functional group-containing intraocular lenses |
| US6972033B2 (en) * | 2002-08-26 | 2005-12-06 | Advanced Medical Optics, Inc. | Accommodating intraocular lens assembly with multi-functional capsular bag ring |
| US20040082993A1 (en) | 2002-10-25 | 2004-04-29 | Randall Woods | Capsular intraocular lens implant having a refractive liquid therein |
| US7662180B2 (en) | 2002-12-05 | 2010-02-16 | Abbott Medical Optics Inc. | Accommodating intraocular lens and method of manufacture thereof |
| US8673339B2 (en) * | 2003-03-11 | 2014-03-18 | Medtronic, Inc. | Demand-release bioactive composition for implantable medical devices |
| US7628810B2 (en) | 2003-05-28 | 2009-12-08 | Acufocus, Inc. | Mask configured to maintain nutrient transport without producing visible diffraction patterns |
| US20050046794A1 (en) | 2003-06-17 | 2005-03-03 | Silvestrini Thomas A. | Method and apparatus for aligning a mask with the visual axis of an eye |
| US7247387B1 (en) | 2003-07-24 | 2007-07-24 | Sepax Technologies Inc. | Material and process for controlled thin polymeric coatings on plastic surface |
| US20050131534A1 (en) * | 2003-11-14 | 2005-06-16 | Rozakis George W. | Posterior chamber phakic intraocular lens |
| US20050131535A1 (en) | 2003-12-15 | 2005-06-16 | Randall Woods | Intraocular lens implant having posterior bendable optic |
| JP4896737B2 (en) | 2003-12-29 | 2012-03-14 | アボット・メディカル・オプティクス・インコーポレイテッド | Intraocular lens with visible light selective transmission region |
| US7278737B2 (en) | 2004-04-30 | 2007-10-09 | Advanced Medical Optics, Inc. | Ophthalmic devices having a highly selective violet light transmissive filter and related methods |
| WO2006083328A2 (en) * | 2004-09-15 | 2006-08-10 | Massachusetts Institute Of Technology | Biologically active surfaces and methods of their use |
| US20060115516A1 (en) * | 2004-11-22 | 2006-06-01 | Pearson Jason C | Copolymerizable methine and anthraquinone compounds and articles containing them |
| ATE499620T1 (en) * | 2004-11-22 | 2011-03-15 | Abbott Medical Optics Inc | COPOLYMERIZABLE AZO COMPOUNDS AND ARTICLES THEREOF |
| US7976577B2 (en) * | 2005-04-14 | 2011-07-12 | Acufocus, Inc. | Corneal optic formed of degradation resistant polymer |
| US20060257355A1 (en) * | 2005-05-10 | 2006-11-16 | Abiomed, Inc. | Impregnated polymer compositions and devices using them |
| US9636213B2 (en) | 2005-09-30 | 2017-05-02 | Abbott Medical Optics Inc. | Deformable intraocular lenses and lens systems |
| US20080002146A1 (en) * | 2006-06-28 | 2008-01-03 | Stachowski Mark J | Biocompatible, surface modified materials |
| WO2008042891A2 (en) * | 2006-10-02 | 2008-04-10 | Oregan Biomedical Engineering Institute, Inc. | Chitosan ophthalmic devices and methods |
| AU2007338100B2 (en) | 2006-12-22 | 2014-01-30 | Amo Groningen Bv | Accommodating intraocular lens, lens system and frame therefor |
| US20080161914A1 (en) | 2006-12-29 | 2008-07-03 | Advanced Medical Optics, Inc. | Pre-stressed haptic for accommodating intraocular lens |
| US7713299B2 (en) | 2006-12-29 | 2010-05-11 | Abbott Medical Optics Inc. | Haptic for accommodating intraocular lens |
| WO2008083283A2 (en) | 2006-12-29 | 2008-07-10 | Advanced Medical Optics, Inc. | Multifocal accommodating intraocular lens |
| US20090228101A1 (en) | 2007-07-05 | 2009-09-10 | Visiogen, Inc. | Intraocular lens with post-implantation adjustment capabilities |
| US8174502B2 (en) * | 2008-03-04 | 2012-05-08 | Apple Inc. | Touch event processing for web pages |
| US7781554B2 (en) | 2008-03-05 | 2010-08-24 | Bausch & Lomb Incorporated | Polysiloxanes and polysiloxane prepolymers with vinyl or epoxy functionality |
| US8034108B2 (en) | 2008-03-28 | 2011-10-11 | Abbott Medical Optics Inc. | Intraocular lens having a haptic that includes a cap |
| CN102177180A (en) | 2008-04-04 | 2011-09-07 | 犹他州大学研究基金会 | Alkylated sem-synthetic glycosaminoglycosan ethers, and methods for making and using thereof |
| WO2010077646A2 (en) * | 2008-12-30 | 2010-07-08 | Bausch & Lomb Incorporated | Method of applying renewable polymeric lens coating |
| NL2002540C2 (en) | 2009-02-17 | 2010-08-18 | Oculentis B V | Ophthalmic lens with optical sectors. |
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| EP2445446B1 (en) | 2009-06-26 | 2019-01-09 | Johnson & Johnson Surgical Vision, Inc. | Accommodating intraocular lenses |
| AU2010279561B2 (en) | 2009-08-03 | 2014-11-27 | Johnson & Johnson Surgical Vision, Inc. | Intraocular lens for providing accomodative vision |
| IN2012DN02153A (en) | 2009-08-13 | 2015-08-07 | Acufocus Inc | |
| US10004593B2 (en) | 2009-08-13 | 2018-06-26 | Acufocus, Inc. | Intraocular lens with elastic mask |
| AU2010282311B2 (en) | 2009-08-13 | 2015-08-13 | Acufocus, Inc. | Masked intraocular implants and lenses |
| CA2830933A1 (en) | 2011-03-23 | 2012-09-27 | University Of Utah Research Foundation | Methods for treating or preventing urological inflammation |
| US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
| EP4193907A1 (en) | 2011-09-13 | 2023-06-14 | Glaukos Corporation | Intraocular physiological sensor |
| EP2785296B1 (en) | 2011-12-02 | 2018-06-20 | AcuFocus, Inc. | Ocular mask having selective spectral transmission |
| US9084674B2 (en) | 2012-05-02 | 2015-07-21 | Abbott Medical Optics Inc. | Intraocular lens with shape changing capability to provide enhanced accomodation and visual acuity |
| WO2014152017A1 (en) | 2013-03-21 | 2014-09-25 | Shifamed Holdings, Llc | Accommodating intraocular lens |
| US9486311B2 (en) | 2013-02-14 | 2016-11-08 | Shifamed Holdings, Llc | Hydrophilic AIOL with bonding |
| US9730638B2 (en) | 2013-03-13 | 2017-08-15 | Glaukos Corporation | Intraocular physiological sensor |
| US9204962B2 (en) | 2013-03-13 | 2015-12-08 | Acufocus, Inc. | In situ adjustable optical mask |
| US9427922B2 (en) | 2013-03-14 | 2016-08-30 | Acufocus, Inc. | Process for manufacturing an intraocular lens with an embedded mask |
| EP2981556A4 (en) * | 2013-04-02 | 2016-11-30 | Univ California | Ethylsulfonated hyaluronic acid biopolymers and methods of use thereof |
| US20150342875A1 (en) | 2014-05-29 | 2015-12-03 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| CN107106293B (en) | 2014-08-26 | 2019-07-12 | 施菲姆德控股有限责任公司 | Modulability intraocular lens |
| US9943403B2 (en) | 2014-11-19 | 2018-04-17 | Acufocus, Inc. | Fracturable mask for treating presbyopia |
| WO2017040853A1 (en) | 2015-09-02 | 2017-03-09 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
| US11564833B2 (en) | 2015-09-25 | 2023-01-31 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
| EP3359987B1 (en) | 2015-10-05 | 2024-02-28 | AcuFocus, Inc. | Methods of molding intraocular lenses |
| US11141263B2 (en) | 2015-11-18 | 2021-10-12 | Shifamed Holdings, Llc | Multi-piece accommodating intraocular lens |
| EP3384342B1 (en) | 2015-11-24 | 2021-08-25 | AcuFocus, Inc. | Toric small aperture intraocular lens with extended depth of focus |
| US11318043B2 (en) | 2016-04-20 | 2022-05-03 | Dose Medical Corporation | Bioresorbable ocular drug delivery device |
| WO2018053111A1 (en) | 2016-09-15 | 2018-03-22 | University Of Utah Research Foundation | In situ gelling compositions for the treatment or prevention of inflammation and tissue damage |
| US10350056B2 (en) | 2016-12-23 | 2019-07-16 | Shifamed Holdings, Llc | Multi-piece accommodating intraocular lenses and methods for making and using same |
| CN106730051B (en) * | 2016-12-27 | 2020-05-01 | 生纳科技(上海)有限公司 | Anticoagulation polymer biological material and preparation method and application thereof |
| US10987214B2 (en) | 2017-05-30 | 2021-04-27 | Shifamed Holdings, Llc | Surface treatments for accommodating intraocular lenses and associated methods and devices |
| EP3634309B1 (en) | 2017-06-07 | 2023-05-24 | Shifamed Holdings, LLC | Adjustable optical power intraocular lenses |
| US11707354B2 (en) | 2017-09-11 | 2023-07-25 | Amo Groningen B.V. | Methods and apparatuses to increase intraocular lenses positional stability |
| WO2019094768A1 (en) * | 2017-11-10 | 2019-05-16 | Kraff Manus | Intraocular lens |
| WO2019217471A1 (en) | 2018-05-09 | 2019-11-14 | Acufocus, Inc. | Intraocular implant with removable optic |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US598861A (en) * | 1898-02-08 | Mechanical movement for windmills | ||
| US839084A (en) * | 1905-10-18 | 1906-12-18 | Anti Friction Journal Box Company | Roller-bearing. |
| US3766167A (en) * | 1971-03-26 | 1973-10-16 | Research Corp | Orally active anticoagulant |
| US4170043A (en) * | 1977-11-30 | 1979-10-09 | American Hospital Supply Corporation | Coated intraocular lens and surgical tool |
| US4174543A (en) * | 1978-06-01 | 1979-11-20 | Kelman Charles D | Intraocular lenses |
| US4240163A (en) * | 1979-01-31 | 1980-12-23 | Galin Miles A | Medicament coated intraocular lens |
| US4249271A (en) * | 1979-07-13 | 1981-02-10 | Stanley Poler | Intraocular lens |
| US4343050A (en) * | 1980-07-14 | 1982-08-10 | Kelman Charles D | Intraocular lenses |
| US4504981A (en) * | 1981-09-28 | 1985-03-19 | Walman Gerald B | Intraocular lens |
| US4437194A (en) * | 1982-02-25 | 1984-03-20 | Optical Radiation Corp. | Intraocular lens assembly |
| US4478981A (en) * | 1982-03-22 | 1984-10-23 | Petrarch Systems Inc. | Mixtures of polyacrylate resins and siloxane carbonate copolymers |
| US4613517A (en) * | 1983-04-27 | 1986-09-23 | Becton, Dickinson And Company | Heparinization of plasma treated surfaces |
| CA1215676A (en) * | 1983-04-27 | 1986-12-23 | Terry S. Dunn | Heparinization of plasma treated substrates |
| US4448718A (en) * | 1983-09-13 | 1984-05-15 | Massachusetts Institute Of Technology | Method for the preparation of collagen-glycosaminoglycan composite materials |
| US4502162A (en) * | 1983-10-07 | 1985-03-05 | Coopervision, Inc. | Haptic for intraocular lens |
| US4687484A (en) * | 1983-12-12 | 1987-08-18 | Kaplan Linda J | Anterior chamber intraocular lens |
| US4681585A (en) * | 1984-04-11 | 1987-07-21 | Intermedics Intraocular, Inc. | Intraocular implant |
| SU1546084A1 (en) * | 1984-04-25 | 1990-02-28 | Московский научно-исследовательский институт микрохирургии глаза | Method of manufacturing artificial lens of the eye |
| SE442820B (en) * | 1984-06-08 | 1986-02-03 | Pharmacia Ab | GEL OF THE CROSS-BOND HYALURONIC ACID FOR USE AS A GLASS BODY SUBSTITUTE |
| GB2165456A (en) * | 1984-10-12 | 1986-04-16 | Mo Nii Mikrokhirurgi | Intra-occular prosthetic lens |
| US4731080A (en) * | 1985-01-18 | 1988-03-15 | Galin Miles A | Coated intraocular lens |
| US4713244A (en) * | 1985-08-16 | 1987-12-15 | Bausch & Lomb Incorporated | Sustained-release formulation containing an amino acid polymer with a lower alkyl (C1 -C4) polar solvent |
| US4722867A (en) * | 1986-04-16 | 1988-02-02 | Gregory Halpern | Albumin-enhanced polysaccharide solution |
| US4826478A (en) * | 1986-06-23 | 1989-05-02 | Stanley Schocket | Anterior chamber tube shunt to an encircling band, and related surgical procedure |
| US4676792A (en) * | 1986-08-26 | 1987-06-30 | Donald Praeger | Method and artificial intraocular lens device for the phakic treatment of myopia |
| US4840626A (en) * | 1986-09-29 | 1989-06-20 | Johnson & Johnson Patient Care, Inc. | Heparin-containing adhesion prevention barrier and process |
| NO160823C (en) * | 1987-02-11 | 1989-06-07 | Jens G Hetland | DEVICE FOR INTRA-OCULAR ROOM LENS. |
| SU1516111A1 (en) * | 1987-02-16 | 1989-10-23 | Московский научно-исследовательский институт глазных болезней им.Гельмгольца | Method of working the artificial eye lens |
| FR2631228B1 (en) * | 1988-05-11 | 1990-08-10 | Domilens Laboratoires | INTRA-EYE IMPLANT OF PREVIOUS CHAMBER |
| JPH01300959A (en) * | 1988-05-31 | 1989-12-05 | Canon Inc | Intraocular lens having surface functional film |
| US4871363A (en) * | 1988-07-21 | 1989-10-03 | Kelman Charles D | Corrective intraocular lens |
| US5080924A (en) * | 1989-04-24 | 1992-01-14 | Drexel University | Method of making biocompatible, surface modified materials |
| EP0491860B1 (en) * | 1989-09-15 | 1997-01-15 | Chiron Vision Corporation | Synthetic material for supporting the attachment, growth and migration of epithelial cells, prosthetic device for subepithelial implantation and lens treated |
| US5258025A (en) * | 1990-11-21 | 1993-11-02 | Fedorov Svjatoslav N | Corrective intraocular lens |
| WO1993003776A1 (en) * | 1991-08-16 | 1993-03-04 | Galin Miles A | Medicament coated refractive anterior chamber ocular implant |
-
1992
- 1992-08-13 WO PCT/US1992/006818 patent/WO1993003776A1/en active IP Right Grant
- 1992-08-13 BR BR9206365A patent/BR9206365A/en not_active Application Discontinuation
- 1992-08-13 AU AU25136/92A patent/AU664858B2/en not_active Ceased
- 1992-08-13 ES ES92918851T patent/ES2149178T3/en not_active Expired - Lifetime
- 1992-08-13 CA CA002115651A patent/CA2115651C/en not_active Expired - Lifetime
- 1992-08-13 EP EP92918851A patent/EP0601055B1/en not_active Expired - Lifetime
- 1992-08-13 AT AT92918851T patent/ATE193654T1/en active IP Right Revival
- 1992-08-13 US US08/193,160 patent/US5652014A/en not_active Expired - Lifetime
- 1992-08-13 UA UA94005438A patent/UA35578C2/en unknown
- 1992-08-13 DE DE69231155T patent/DE69231155T2/en not_active Expired - Lifetime
- 1992-08-13 DK DK92918851T patent/DK0601055T3/en active
- 1992-08-13 SG SG9603913A patent/SG81873A1/en unknown
- 1992-08-13 JP JP5504447A patent/JPH06509731A/en active Pending
- 1992-08-14 MX MX9204726A patent/MX9204726A/en not_active IP Right Cessation
-
1997
- 1997-03-12 US US08/815,895 patent/US5944753A/en not_active Expired - Lifetime
-
1998
- 1998-04-20 US US09/063,624 patent/US6143028A/en not_active Expired - Lifetime
-
2000
- 2000-09-06 GR GR20000402027T patent/GR3034339T3/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX9204726A (en) | 1993-07-01 |
| US6143028A (en) | 2000-11-07 |
| SG81873A1 (en) | 2001-07-24 |
| GR3034339T3 (en) | 2000-12-29 |
| CA2115651A1 (en) | 1993-03-04 |
| BR9206365A (en) | 1994-10-11 |
| ES2149178T3 (en) | 2000-11-01 |
| AU664858B2 (en) | 1995-12-07 |
| EP0601055A1 (en) | 1994-06-15 |
| AU2513692A (en) | 1993-03-16 |
| DE69231155T2 (en) | 2001-02-15 |
| JPH06509731A (en) | 1994-11-02 |
| ATE193654T1 (en) | 2000-06-15 |
| DK0601055T3 (en) | 2000-10-02 |
| DE69231155D1 (en) | 2000-07-13 |
| US5944753A (en) | 1999-08-31 |
| EP0601055B1 (en) | 2000-06-07 |
| WO1993003776A1 (en) | 1993-03-04 |
| UA35578C2 (en) | 2001-04-16 |
| US5652014A (en) | 1997-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2115651C (en) | Medicament coated refractive anterior chamber ocular implant | |
| US4731080A (en) | Coated intraocular lens | |
| EP1196115B1 (en) | Positive power anterior chamber ocular implant | |
| US4240163A (en) | Medicament coated intraocular lens | |
| JP3902224B2 (en) | Method and means for preventing secondary cataract | |
| Allarakhia et al. | Soft intraocular lenses | |
| US6187042B1 (en) | Intraocular lens coating compositions | |
| US6454802B1 (en) | Intraocular lens implant for the prevention of secondary cataracts | |
| TW200840554A (en) | Coated medical implants and lenses | |
| AU4278496A (en) | Modulation of cell proliferation and wound healing | |
| EP1810700B1 (en) | Method of producing surface-treated intraocular lens and intraocular lens for inhibiting secondary cataract | |
| Smetana Jr et al. | Intraocular biocompatibility of hydroxyethyl methacrylate and methacrylic acid copolymer/partially hydrolyzed poly (2‐hydroxyethyl methacrylate) | |
| EP0954341B1 (en) | Intraocular lens containing releasable medication | |
| US20110082543A1 (en) | Methods and Devices for Preventing or Delaying Posterior Capsule Opacification | |
| Fagerholm et al. | Corneal endothelial protection by heparin and sodium hyaluronate surface coating of PMMA intraocular lenses | |
| Blumenthal et al. | Interaction of soft and hard intraocular lenses with cat cornea endothelium | |
| Tripti et al. | Materials for intraocular lenses (IOLs): Review of developments to achieve biocompatibility | |
| US20010003162A1 (en) | Toric intraocular lens materials | |
| Legeais | Materials for intraocular lenses | |
| WO2000000106A1 (en) | Antioxidant intraocular lens | |
| Giordano et al. | Biomaterials in ophthalmology | |
| Gupta et al. | Intraocular Lens and Biocompatibility-A Review | |
| Wnek et al. | Ocular Implants/Andrew W. Lloyd, Susan Sandeman, Richard GA Faragher, Stephen P. Denyer | |
| FR2909285A1 (en) | Use of an injectable or implantable antiadhesive antifibrotic gel based on a crosslinked natural or synthetic polymer for treating glaucoma or surgical wounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |