WO2010023705A1 - Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders - Google Patents
Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders Download PDFInfo
- Publication number
- WO2010023705A1 WO2010023705A1 PCT/IT2009/000392 IT2009000392W WO2010023705A1 WO 2010023705 A1 WO2010023705 A1 WO 2010023705A1 IT 2009000392 W IT2009000392 W IT 2009000392W WO 2010023705 A1 WO2010023705 A1 WO 2010023705A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- enhancers
- riboflavin
- corneal
- use according
- present
- Prior art date
Links
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 title claims abstract description 54
- 239000003623 enhancer Substances 0.000 title claims abstract description 30
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 239000002151 riboflavin Substances 0.000 title claims abstract description 27
- 235000019192 riboflavin Nutrition 0.000 title claims abstract description 27
- 229960002477 riboflavin Drugs 0.000 title claims abstract description 27
- 239000000203 mixture Substances 0.000 title claims abstract description 22
- 201000002287 Keratoconus Diseases 0.000 title claims abstract description 19
- 238000004132 cross linking Methods 0.000 title claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 10
- 238000000034 method Methods 0.000 claims abstract description 14
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 8
- 229960000281 trometamol Drugs 0.000 claims description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 7
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 claims description 6
- -1 Chemical compound 0.000 claims description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 4
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 claims description 4
- 229950001574 riboflavin phosphate Drugs 0.000 claims description 4
- BGLGAKMTYHWWKW-UHFFFAOYSA-N acridine yellow Chemical compound [H+].[Cl-].CC1=C(N)C=C2N=C(C=C(C(C)=C3)N)C3=CC2=C1 BGLGAKMTYHWWKW-UHFFFAOYSA-N 0.000 claims description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 3
- 229960000907 methylthioninium chloride Drugs 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 3
- 229940068968 polysorbate 80 Drugs 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 229960001404 quinidine Drugs 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 239000005639 Lauric acid Substances 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 claims description 2
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 claims description 2
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 2
- QLBHNVFOQLIYTH-UHFFFAOYSA-L dipotassium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [K+].[K+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O QLBHNVFOQLIYTH-UHFFFAOYSA-L 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims description 2
- IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 claims description 2
- 239000004174 erythrosine Substances 0.000 claims description 2
- 235000012732 erythrosine Nutrition 0.000 claims description 2
- 229940011411 erythrosine Drugs 0.000 claims description 2
- 229940041616 menthol Drugs 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- VMSNAUAEKXEYGP-YEUHZSMFSA-M sodium glycodeoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 VMSNAUAEKXEYGP-YEUHZSMFSA-M 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 229960004025 sodium salicylate Drugs 0.000 claims description 2
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 claims description 2
- 229940045946 sodium taurodeoxycholate Drugs 0.000 claims description 2
- YXHRQQJFKOHLAP-FVCKGWAHSA-M sodium;2-[[(4r)-4-[(3r,5r,8r,9s,10s,12s,13r,14s,17r)-3,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 YXHRQQJFKOHLAP-FVCKGWAHSA-M 0.000 claims description 2
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 claims description 2
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- XTDRLNBNAYMGCW-UHFFFAOYSA-N methyl 2-hydroxybenzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1O XTDRLNBNAYMGCW-UHFFFAOYSA-N 0.000 claims 1
- 208000021921 corneal disease Diseases 0.000 abstract description 4
- 210000004087 cornea Anatomy 0.000 description 16
- 238000010521 absorption reaction Methods 0.000 description 8
- 210000003683 corneal stroma Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 210000003560 epithelium corneal Anatomy 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 230000002165 photosensitisation Effects 0.000 description 4
- 239000003504 photosensitizing agent Substances 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000001949 anaesthesia Methods 0.000 description 2
- 201000009310 astigmatism Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 201000004573 corneal ectasia Diseases 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 238000005213 imbibition Methods 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- CIHKVMHPDDJIIP-UHFFFAOYSA-N 2-methylperoxybenzoic acid Chemical compound COOC1=CC=CC=C1C(O)=O CIHKVMHPDDJIIP-UHFFFAOYSA-N 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- RAGZEDHHTPQLAI-UHFFFAOYSA-L disodium;2',4',5',7'-tetraiodo-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C([O-])C(I)=C1OC1=C(I)C([O-])=C(I)C=C21 RAGZEDHHTPQLAI-UHFFFAOYSA-L 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 230000000065 osmolyte Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 208000017983 photosensitivity disease Diseases 0.000 description 1
- 231100000434 photosensitization Toxicity 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/49—Cinchonan derivatives, e.g. quinine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to the use of enhancers for the preparation of ophthalmic compositions (in particular collyriums) possibly containing riboflavin, designed to imbibe the corneal stroma without having to proceed, in order to obtain said imbibition, to the removal of the corneal epithelium (de-epithelization) in the practice of the treatment of keratoconus, or other ectasic corneal disorders, by means of cross-linking, and also relates to the corresponding ophthalmic compositions for the technique of corneal cross-linking.
- enhancers for the preparation of ophthalmic compositions (in particular collyriums) possibly containing riboflavin, designed to imbibe the corneal stroma without having to proceed, in order to obtain said imbibition, to the removal of the corneal epithelium (de-epithelization) in the practice of the treatment of keratoconus, or other ectasic corneal disorders, by means of cross-link
- Keratoconus is a serious disease of the cornea since it is a non-inflammatory progressive dystrophy that each year affects approximately 50 persons in every 100 000, generally young people of between 10 and 20 years of age. Keratoconus is a genetic disease with a higher frequency amongst females and at times appears to be correlated to dysfunctions of endocrine glands (hypophysis and thyroid) . It can affect both eyes in approximately 85% of cases and has an evolution that may vary from subject to subject.
- the top of keratoconus becomes opaque on account of an alteration in the nutriment of that part of the cornea, which in the most acute forms can present a corneal curvature of more than 62D and reach a corneal thickness of even 446 ⁇ m. If the disease is neglected, the top can ulcerate with consequent perforation of the cornea; there appear pain, lacrimation and spasm of the eyelids.
- lamellar keratoplasty was introduced in Italy for the treatment of keratoconus, whereby, in practice, not the entire cornea is replaced, but only the outer thickness, i.e., the part affected by the disease.
- Corneal cross-linking is a low-invasive method, which uses riboflavin activated by a UV laser (366 nm) ; said method is painless and is carried out in day- hospital.
- Cross-linking enables reinforcement of the structure of the cornea affected by keratoconus through the interweaving and increase in links (cross-linking) between the fibres of the corneal collagen. From the clinical studies conducted, this method has proved able to reduce the astigmatism associated to keratoconus as well as to slow down or arrest evolution of keratoconus,. thus avoiding the need for transplantation of the cornea.
- Corneal cross-linking is carried out by applying a local corneal anaesthesia for making the abrasion of the corneal epithelium (de-epithelization) having a
- Riboflavin in particular riboflavin phosphate, which is commonly used in corneal cross-linking, is a hydrophilic photosensitizing and photopolymerizing molecule with a poor capacity for diffusing through the epithelium and hence reaching the corneal stroma. It is therefore necessary to facilitate absorption thereof and complete imbibition of the corneal stroma before starting the irradiation with UV-A, by means of removal of the corneal epithelium (de-epithelization) . This procedure can create, albeit rarely, complications at a corneal level, pain, in addition to being a method that renders the task of the oculist more difficult.
- bio-enhancers i.e., substances that favour the passage of riboflavin or of other photosensitizing and photopolymerizing substances through the corneal epithelium, enabling absorption by the corneal stroma itself
- enhancers chosen from among: bio-enhancers (i.e., substances that favour the passage of riboflavin or of other photosensitizing and photopolymerizing substances through the corneal epithelium, enabling absorption by the corneal stroma itself)
- EDTA EDTA
- sodium EDTA sodium EDTA
- potassium EDTA polysorbate 80
- tromethamine azone
- benzalkonium chloride cetylpyridinium chloride, cetyltrimethylammonium chloride, lauric acid, menthol, methoxysalicylate, polyoxyethylene, sodium glycholate, sodium glycodeoxycholate, sodium lauryl sulphate, sodium salicylate, sodium taurocholate, sodium taurod
- an improved corneal cross-linking is obtained by means of an irradiation close to the visible that is less harmful, without any need for de-epithelization.
- the present invention hence envisages the use of the enhancers described above, either alone or variously mixed together, possibly with riboflavin, for the preparation of ophthalmic compositions to be used for cross-linking in keratoconus or in other corneal ectasias .
- the enhancers according to the present invention can be used for application directly on the cornea for cross-linking of keratoconus or other corneal ectasias without proving cytotoxic.
- ophthalmic compositions containing the enhancers mentioned above possibly associated to riboflavin are ophthalmic compositions containing the enhancers mentioned above possibly associated to riboflavin; said ophthalmic composition can be prepared according to known techniques and can contain in particular: one or more bio-enhancers with one or more photo-enhancers and possibly riboflavin; one or more bio-enhancers with possibly riboflavin; one or more photo-enhancers with possibly riboflavin.
- compositions described above containing just one or more bio- enhancers or else one or more photo-enhancers there may possibly be applied directly on the cornea a solution of one or more photosensitizing and photopolymerizing substances, in particular riboflavin.
- bio-enhancers of the present invention are present in appropriate amounts in all the compositions described above chosen between 0.001 wt% and 5 wt% with respect to the composition.
- the enhancer capability depends above all from the EDTA and tromethamine association since the two compounds form together a ion-pair between the EDTA non salified carboxyl and the tromethamine which has a notable membrane penetrative capacity.
- the tromethamine is preferably present at between 0.05 wt% and 0.5 wt%, and EDTA is preferably present at between 0.05 wt% and 0.5 wt%, the riboflavin absorption is immediate.
- the photosensitizing and photopolymerizing substances (photo-enhancers) , amongst which riboflavin, of the present invention are used in appropriate amounts chosen between 0.001 wt% and 1 wt% with respect to the composition.
- the riboflavin preferably used in the present invention is riboflavin phosphate in appropriate amounts in all the compositions described above; in particular it is preferably present at between 0.05 wt% and 0.3 wt% of the composition of the present invention.
- ophthalmic compositions of the present invention can be prepared in the technical form of collyriums, eye-drops, eye-washes, ointments, and in any case in all the pharmaceutical technical forms that enable a corneal application according to known techniques; given hereinafter are examples provided by way of illustration, without this implying any limit to the present invention.
- the dosage of the individual components is expressed in weight percentage.
- formulations 1- 13 may also be isotonic or even hypertonic with the addition of sufficient sodium chloride (or other osmolyte) to achieve said purpose.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
Claims
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BRPI0910368A BRPI0910368B8 (en) | 2008-08-28 | 2009-08-27 | use of one or more bioenhancers, composition for the use of one or more enhancers chosen from bioenhancers and photoenhancers and eye drops for the use of one or more enhancers chosen from bioenhancers and photoenhancers |
EA201100393A EA022055B1 (en) | 2008-08-28 | 2009-08-27 | Use of bio-enhancers for corneal cross-linking |
JP2011524534A JP2012500844A (en) | 2008-08-28 | 2009-08-27 | Use of an enhancer capable of associating with riboflavin and the corresponding ophthalmic composition for corneal cross-linking in the treatment of keratoconus or corneal dilatation |
DK09748494.3T DK2323642T3 (en) | 2008-08-28 | 2009-08-27 | Use of EDTA + tromethamine or photo-enhancers in association with riboflavin for corneal cross-linking in the treatment of keratoconus or other ectatic corneal disorders |
MX2011002234A MX2011002234A (en) | 2008-08-28 | 2009-08-27 | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders. |
MX2013013707A MX358176B (en) | 2008-08-28 | 2009-08-27 | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders. |
PL09748494T PL2323642T3 (en) | 2008-08-28 | 2009-08-27 | Use of EDTA+tromethamine or of photoenhancers, associated to riboflavin for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders |
EP09748494.3A EP2323642B1 (en) | 2008-08-28 | 2009-08-27 | Use of EDTA+tromethamine or of photoenhancers, associated to riboflavin for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders |
CN200980138188.3A CN102164592B (en) | 2008-08-28 | 2009-08-27 | The reinforcing agent that can use together to riboflavin is for the preparation of carrying out the purposes of ophthalmic composition of corneal cross-linking and corresponding ophthalmic composition in the treatment of keratoconus |
ES09748494.3T ES2460578T3 (en) | 2008-08-28 | 2009-08-27 | Use of EDTA + tromethamine or photo-enhancers, associated with riboflavin, for corneal cross-linking in the treatment of keratoconus or other ectatic corneal disorders |
AU2009286285A AU2009286285B2 (en) | 2008-08-28 | 2009-08-27 | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders |
KR1020117006855A KR20110046567A (en) | 2008-08-28 | 2009-08-27 | Corresponding ophthalmic compositions for the use of enhancers, possibly associated with riboflavin, and for corneal crosslinking in the treatment of keratoconus or other corneal dilatation diseases. |
IL211448A IL211448A (en) | 2008-08-28 | 2011-02-27 | Use of bio-enhancers and/or photo-enhancers for preparing ophthalmic compositions comprising riboflavin or riboflavin phosphate for treating corneal ectasic disorders by corneal cross-linking |
US13/036,492 US20110152219A1 (en) | 2008-08-28 | 2011-02-28 | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITRM2008A000472 | 2008-08-28 | ||
ITRM2008A000472A IT1393402B1 (en) | 2008-08-28 | 2008-08-28 | USE OF ENHANCER EVENTUALLY WITH RIBOFLAVIN, AS WELL AS RELATIVE OPHTHALMIC COMPOSITIONS FOR CORNEAL CROSS-LINKING OF KERATOCON OR OTHER ECNEASIC CORNEAL PATHOLOGIES |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/036,492 Continuation-In-Part US20110152219A1 (en) | 2008-08-28 | 2011-02-28 | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010023705A1 true WO2010023705A1 (en) | 2010-03-04 |
Family
ID=40679354
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IT2009/000392 WO2010023705A1 (en) | 2008-08-28 | 2009-08-27 | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders |
Country Status (18)
Country | Link |
---|---|
US (1) | US20110152219A1 (en) |
EP (1) | EP2323642B1 (en) |
JP (1) | JP2012500844A (en) |
KR (1) | KR20110046567A (en) |
CN (1) | CN102164592B (en) |
AU (1) | AU2009286285B2 (en) |
BR (1) | BRPI0910368B8 (en) |
CL (1) | CL2011000378A1 (en) |
DK (1) | DK2323642T3 (en) |
EA (2) | EA022055B1 (en) |
ES (1) | ES2460578T3 (en) |
IL (1) | IL211448A (en) |
IT (1) | IT1393402B1 (en) |
MX (2) | MX358176B (en) |
PE (1) | PE20110287A1 (en) |
PL (1) | PL2323642T3 (en) |
PT (1) | PT2323642E (en) |
WO (1) | WO2010023705A1 (en) |
Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITMI20101236A1 (en) * | 2010-07-05 | 2012-01-06 | Roberto Pinelli | TRANS-EPITHELIAL OSMOTIC COLLIRIUM FOR THE CARE OF THE KERATOCONO. |
WO2012095877A1 (en) * | 2011-01-12 | 2012-07-19 | Sooft Italia Spa | Corneal delivery of cross-linking agents by iontophoresis for the treatment of keratoconus and related ophthalmic compositions |
WO2012158991A2 (en) * | 2011-05-18 | 2012-11-22 | Avedro, Inc. | Controlled application of cross-linking agent |
US8366689B2 (en) | 2008-09-30 | 2013-02-05 | Avedro, Inc. | Method for making structural changes in corneal fibrils |
ITRM20110560A1 (en) * | 2011-10-25 | 2013-04-26 | Sooft Italia Spa | IMPROVED CROSS-LINKING COMPOSITION FOR THE TREATMENT OF KERATOCONUS BY IONTOFORESIS |
US8545487B2 (en) | 2007-12-05 | 2013-10-01 | Avedro Inc. | Eye therapy system |
US8574277B2 (en) | 2009-10-21 | 2013-11-05 | Avedro Inc. | Eye therapy |
RU2542799C1 (en) * | 2013-10-29 | 2015-02-27 | Игорь Борисович Медведев | Method of treating corneal keratoconus |
US9020580B2 (en) | 2011-06-02 | 2015-04-28 | Avedro, Inc. | Systems and methods for monitoring time based photo active agent delivery or photo active marker presence |
US9044308B2 (en) | 2011-05-24 | 2015-06-02 | Avedro, Inc. | Systems and methods for reshaping an eye feature |
EP2830627A4 (en) * | 2012-03-29 | 2015-10-14 | Cxl Ophthalmics Llc | Ocular treatment solutions, delivery devices and delivery augmentation methods |
CN105256059A (en) * | 2015-11-20 | 2016-01-20 | 山东省眼科研究所 | Application of TUBA3D gene in preparing keratoconus diagnosis product |
WO2016174688A1 (en) | 2015-04-29 | 2016-11-03 | Sooft Italia Spa | Improved cross-linking agents of collagen fibers for the use in the treatment of corneal ectasia |
US9498114B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
US9498122B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
US9555111B2 (en) | 2012-03-29 | 2017-01-31 | Cxl Ophthalmics, Llc | Ocular cross-linking system and method for sealing corneal wounds |
US9566301B2 (en) | 2012-03-29 | 2017-02-14 | Cxl Ophthalmics, Llc | Compositions and methods for treating or preventing diseases associated with oxidative stress |
US9622911B2 (en) | 2010-09-30 | 2017-04-18 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
US9700456B2 (en) | 2011-01-12 | 2017-07-11 | Sooft Italia Spa | Device and method for corneal delivery of riboflavin by iontophoresis for the treatment of keratoconus |
US9707126B2 (en) | 2009-10-21 | 2017-07-18 | Avedro, Inc. | Systems and methods for corneal cross-linking with pulsed light |
US10028657B2 (en) | 2015-05-22 | 2018-07-24 | Avedro, Inc. | Systems and methods for monitoring cross-linking activity for corneal treatments |
US20180236077A1 (en) * | 2017-02-21 | 2018-08-23 | Avedro, Inc. | Formulations for eye treatments |
US10114205B2 (en) | 2014-11-13 | 2018-10-30 | Avedro, Inc. | Multipass virtually imaged phased array etalon |
US10258809B2 (en) | 2015-04-24 | 2019-04-16 | Avedro, Inc. | Systems and methods for photoactivating a photosensitizer applied to an eye |
US10350111B2 (en) | 2014-10-27 | 2019-07-16 | Avedro, Inc. | Systems and methods for cross-linking treatments of an eye |
US11179576B2 (en) | 2010-03-19 | 2021-11-23 | Avedro, Inc. | Systems and methods for applying and monitoring eye therapy |
US11207410B2 (en) | 2015-07-21 | 2021-12-28 | Avedro, Inc. | Systems and methods for treatments of an eye with a photosensitizer |
US11642244B2 (en) | 2019-08-06 | 2023-05-09 | Avedro, Inc. | Photoactivation systems and methods for corneal cross-linking treatments |
US11766356B2 (en) | 2018-03-08 | 2023-09-26 | Avedro, Inc. | Micro-devices for treatment of an eye |
US12016794B2 (en) | 2018-10-09 | 2024-06-25 | Avedro, Inc. | Photoactivation systems and methods for corneal cross-linking treatments |
US12042433B2 (en) | 2018-03-05 | 2024-07-23 | Avedro, Inc. | Systems and methods for eye tracking during eye treatment |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110280763A1 (en) * | 2010-05-17 | 2011-11-17 | Abbott Medical Optics Inc. | Light-activated disinfection system |
RU2481809C1 (en) * | 2011-12-21 | 2013-05-20 | Федеральное государственное учреждение "Межотраслевой научно-технический комплекс "Микрохирургия глаза" имени академика С.Н. Федорова Федерального агентства по высокотехнологичной медицинской помощи" | Method of treating post-lasik keratectasia |
RU2487691C1 (en) * | 2012-04-12 | 2013-07-20 | Федеральное государственное бюджетное учреждение "Межотраслевой научно-технический комплекс "Микрохирургия глаза" имени академика С.Н. Федорова" Министерства здравоохранения и социального развития Российской Федерации | Method of treating keratoconus |
PL2948113T3 (en) * | 2013-01-28 | 2018-08-31 | Novartis Ag | Apparatus for corneal crosslinking |
WO2014189849A1 (en) * | 2013-05-19 | 2014-11-27 | Avedro, Inc. | Systems, methods, and compositions for cross-linking |
US9931199B2 (en) * | 2014-05-05 | 2018-04-03 | Roberto Gustavo ALBERTAZZI | Methods and apparatus for treating keratoconus |
US11259914B2 (en) | 2014-05-12 | 2022-03-01 | Gholam A. Peyman | Molding or 3-D printing of a synthetic refractive corneal lenslet |
US9744029B1 (en) | 2014-05-12 | 2017-08-29 | Gholam A. Peyman | Method of preventing capsular opacification and fibrosis utilizing an accommodative intraocular lens implant |
US10206569B1 (en) | 2014-05-12 | 2019-02-19 | Gholam A. Peyman | Corneal intraocular pressure sensor and a surgical method using the same |
US10881503B2 (en) | 2014-05-12 | 2021-01-05 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
US10278920B1 (en) | 2014-05-12 | 2019-05-07 | Gholam A. Peyman | Drug delivery implant and a method using the same |
US11045352B2 (en) | 2014-05-12 | 2021-06-29 | Gholam A. Peyman | Methods for treatment of dry eye and other acute or chronic inflammatory processes |
US10709546B2 (en) | 2014-05-12 | 2020-07-14 | Gholam A. Peyman | Intracorneal lens implantation with a cross-linked cornea |
US10314690B1 (en) | 2014-05-12 | 2019-06-11 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
US10925889B2 (en) | 2014-05-12 | 2021-02-23 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
US11338059B2 (en) | 2014-05-12 | 2022-05-24 | Gholam A. Peyman | Method of corneal and scleral inlay crosslinking and preservation |
US9937033B1 (en) | 2014-05-12 | 2018-04-10 | Gholam A. Peyman | Corneal lenslet implantation with a cross-linked cornea |
US10195081B1 (en) | 2014-05-12 | 2019-02-05 | Gholam A. Peyman | Method of prevention of capsular opacification and fibrosis after cataract extraction and/or prevention of fibrosis around a shunt or stent after glaucoma surgery |
US10583221B2 (en) | 2014-05-12 | 2020-03-10 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
US9427355B1 (en) * | 2014-05-12 | 2016-08-30 | Gholam A. Peyman | Corneal transplantation with a cross-linked cornea |
US11666777B2 (en) | 2014-05-12 | 2023-06-06 | Gholam A. Peyman | Photodynamic therapy technique for preventing damage to the fovea of the eye or another body portion of a patient |
US11648261B2 (en) | 2014-05-12 | 2023-05-16 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
US11565023B2 (en) | 2014-05-12 | 2023-01-31 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
ITUB20160237A1 (en) * | 2016-01-26 | 2017-07-26 | Vision Engineering Italy Soc A Responsabilita Limitata | PROCEDURE FOR CONTROL OF THE DOSAGE OF A CHROMOPHOROR AGENT IN A CORNEAL FABRIC AND PROCEDURE FOR DOSING A CHROMOPHOROR AGENT IN A CORNEAL FABRIC |
US10342697B2 (en) | 2016-04-13 | 2019-07-09 | Avedro, Inc. | Systems and methods for delivering drugs to an eye |
US11707518B2 (en) | 2019-04-28 | 2023-07-25 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
CN110314034B (en) * | 2019-08-08 | 2021-12-03 | 南京市第一医院 | Cornea cross-linking device capable of realizing individual therapy |
US11458220B2 (en) | 2020-11-12 | 2022-10-04 | Singletto Inc. | Microbial disinfection for personal protection equipment |
CN115177729B (en) * | 2022-08-03 | 2023-09-26 | 山东第一医科大学附属眼科研究所(山东省眼科研究所、山东第一医科大学附属青岛眼科医院) | Application of adrenergic receptor agonist in preparation of keratoconus crosslinking permeation promoter |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004058289A1 (en) * | 2002-12-20 | 2004-07-15 | Chakshu Research, Inc. | Ophthalmic formulation for the prevention and treatment of ocular conditions |
US20060222597A1 (en) * | 1997-10-01 | 2006-10-05 | Novadel Pharma Inc. | Buccal, polar and non-polar sprays containing propofol |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1200698C (en) | 1998-03-09 | 2005-05-11 | 伊斯塔药品公司 | Use of corneal hardening agent in enzyme orthokeratology |
US6174524B1 (en) | 1999-03-26 | 2001-01-16 | Alcon Laboratories, Inc. | Gelling ophthalmic compositions containing xanthan gum |
AU2001249984B2 (en) * | 2000-02-11 | 2005-05-26 | The General Hospital Corporation | Photochemical tissue bonding |
ITRM20050443A1 (en) * | 2005-08-12 | 2007-02-13 | Opocrin Spa | OPHTHALMIC PREPARATIONS BASED ON MUCO-ADHESIVE POLYSACCHARIDES WITH A RECYCLABLE CAPACITY OF CORNEA. |
US20120203161A1 (en) * | 2009-08-12 | 2012-08-09 | Seros Medical, Llc | Deuterated water and riboflavin solution for extending singlet oxygen lifetimes in treatment of ocular tissue and method of use |
-
2008
- 2008-08-28 IT ITRM2008A000472A patent/IT1393402B1/en active
-
2009
- 2009-08-27 MX MX2013013707A patent/MX358176B/en unknown
- 2009-08-27 CN CN200980138188.3A patent/CN102164592B/en active Active
- 2009-08-27 PL PL09748494T patent/PL2323642T3/en unknown
- 2009-08-27 BR BRPI0910368A patent/BRPI0910368B8/en active IP Right Grant
- 2009-08-27 EA EA201100393A patent/EA022055B1/en not_active IP Right Cessation
- 2009-08-27 EA EA201300272A patent/EA023607B1/en not_active IP Right Cessation
- 2009-08-27 WO PCT/IT2009/000392 patent/WO2010023705A1/en active Application Filing
- 2009-08-27 DK DK09748494.3T patent/DK2323642T3/en active
- 2009-08-27 AU AU2009286285A patent/AU2009286285B2/en active Active
- 2009-08-27 ES ES09748494.3T patent/ES2460578T3/en active Active
- 2009-08-27 PT PT97484943T patent/PT2323642E/en unknown
- 2009-08-27 KR KR1020117006855A patent/KR20110046567A/en not_active Application Discontinuation
- 2009-08-27 PE PE2011000192A patent/PE20110287A1/en not_active Application Discontinuation
- 2009-08-27 JP JP2011524534A patent/JP2012500844A/en active Pending
- 2009-08-27 MX MX2011002234A patent/MX2011002234A/en active IP Right Grant
- 2009-08-27 EP EP09748494.3A patent/EP2323642B1/en active Active
-
2011
- 2011-02-22 CL CL2011000378A patent/CL2011000378A1/en unknown
- 2011-02-27 IL IL211448A patent/IL211448A/en active IP Right Grant
- 2011-02-28 US US13/036,492 patent/US20110152219A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060222597A1 (en) * | 1997-10-01 | 2006-10-05 | Novadel Pharma Inc. | Buccal, polar and non-polar sprays containing propofol |
WO2004058289A1 (en) * | 2002-12-20 | 2004-07-15 | Chakshu Research, Inc. | Ophthalmic formulation for the prevention and treatment of ocular conditions |
Non-Patent Citations (4)
Title |
---|
See also references of EP2323642A1 * |
SPOERL E, SEILER T.: "Techniques for stiffening the cornea", J REFRACT SURG. 1999 NOV-DEC;15(6):711-3, 1999, University Eye Clinic, Dresden, Germany., XP008107084 * |
SPOERL: "Induction of cross-linking in...", EXP EYE RES, no. 66, 1998, pages 97 - 103, XP008107083 * |
WOLLENSAK GREGOR ET AL: "Collagen crosslinking of human and porcine sclera", JOURNAL CATARACT AND REFRACTIVE SURGERY, SURGERY, FAIRFAX, VA, vol. 30, no. 3, 2004, pages 689 - 695, XP002450030, ISSN: 0886-3350 * |
Cited By (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8545487B2 (en) | 2007-12-05 | 2013-10-01 | Avedro Inc. | Eye therapy system |
US8366689B2 (en) | 2008-09-30 | 2013-02-05 | Avedro, Inc. | Method for making structural changes in corneal fibrils |
US8870934B2 (en) | 2009-10-21 | 2014-10-28 | Avedro, Inc. | Eye therapy system |
US9498642B2 (en) | 2009-10-21 | 2016-11-22 | Avedro, Inc. | Eye therapy system |
US8574277B2 (en) | 2009-10-21 | 2013-11-05 | Avedro Inc. | Eye therapy |
US9707126B2 (en) | 2009-10-21 | 2017-07-18 | Avedro, Inc. | Systems and methods for corneal cross-linking with pulsed light |
US11179576B2 (en) | 2010-03-19 | 2021-11-23 | Avedro, Inc. | Systems and methods for applying and monitoring eye therapy |
ITMI20101236A1 (en) * | 2010-07-05 | 2012-01-06 | Roberto Pinelli | TRANS-EPITHELIAL OSMOTIC COLLIRIUM FOR THE CARE OF THE KERATOCONO. |
WO2012004726A1 (en) | 2010-07-05 | 2012-01-12 | Roberto Pinelli | Trans-epithelial osmotic collyrium for the treatment of keratoconus |
US11135090B2 (en) | 2010-09-30 | 2021-10-05 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
US9622911B2 (en) | 2010-09-30 | 2017-04-18 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
US10285857B2 (en) | 2010-09-30 | 2019-05-14 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
US11033429B2 (en) | 2010-09-30 | 2021-06-15 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
CN103384514A (en) * | 2011-01-12 | 2013-11-06 | 索夫特意大利公司 | Corneal delivery of cross-linking agents by iontophoresis for the treatment of keratoconus and related ophthalmic compositions |
JP2014503552A (en) * | 2011-01-12 | 2014-02-13 | ソーフト イタリア エスピーエー | Corneal delivery of cross-linking agents by iontophoresis and related ophthalmic compositions for the treatment of keratoconus |
EP2663281A1 (en) | 2011-01-12 | 2013-11-20 | Sooft Italia Spa | Corneal delivery of cross-linking agents by iontophoresis for the treatment of keratoconus and related ophthalmic compositions |
US9700456B2 (en) | 2011-01-12 | 2017-07-11 | Sooft Italia Spa | Device and method for corneal delivery of riboflavin by iontophoresis for the treatment of keratoconus |
WO2012095877A1 (en) * | 2011-01-12 | 2012-07-19 | Sooft Italia Spa | Corneal delivery of cross-linking agents by iontophoresis for the treatment of keratoconus and related ophthalmic compositions |
WO2012158991A3 (en) * | 2011-05-18 | 2013-02-28 | Avedro, Inc. | Controlled application of cross-linking agent |
WO2012158991A2 (en) * | 2011-05-18 | 2012-11-22 | Avedro, Inc. | Controlled application of cross-linking agent |
US9044308B2 (en) | 2011-05-24 | 2015-06-02 | Avedro, Inc. | Systems and methods for reshaping an eye feature |
US9020580B2 (en) | 2011-06-02 | 2015-04-28 | Avedro, Inc. | Systems and methods for monitoring time based photo active agent delivery or photo active marker presence |
US10137239B2 (en) | 2011-06-02 | 2018-11-27 | Avedro, Inc. | Systems and methods for monitoring time based photo active agent delivery or photo active marker presence |
EA026703B1 (en) * | 2011-10-25 | 2017-05-31 | Соофт Италия Спа | Riboflavin-comprising ophthalmic composition delivered by iontophoresis, useful for the treatment of keratoconus |
US9439908B2 (en) | 2011-10-25 | 2016-09-13 | Sooft Italia Spa | Cross-linking composition delivered by iontophoresis, useful for the treatment of keratoconus |
JP2014530904A (en) * | 2011-10-25 | 2014-11-20 | ソーフト イタリア エスピーエー | Improved cross-linking composition effective for the treatment of keratoconus and introduced by iontophoresis |
WO2013061350A1 (en) * | 2011-10-25 | 2013-05-02 | Sooft Italia Spa | Improved cross-linking composition delivered by iontophoresis, useful for the treatment of keratoconus |
ITRM20110560A1 (en) * | 2011-10-25 | 2013-04-26 | Sooft Italia Spa | IMPROVED CROSS-LINKING COMPOSITION FOR THE TREATMENT OF KERATOCONUS BY IONTOFORESIS |
AU2012327916B2 (en) * | 2011-10-25 | 2016-04-21 | Sooft Italia Spa | Improved cross-linking composition delivered by iontophoresis, useful for the treatment of keratoconus |
US10729716B2 (en) | 2012-03-29 | 2020-08-04 | Cxl Ophthalmics, Llc | Compositions and methods for treating or preventing diseases associated with oxidative stress |
US11931291B2 (en) | 2012-03-29 | 2024-03-19 | Epion Therapeutics, Inc. | Ophthalmic treatment solution delivery devices and delivery augmentation methods |
US11497766B2 (en) | 2012-03-29 | 2022-11-15 | Cxl Ophthalmics, Llc | Compositions and methods for treating or preventing diseases associated with oxidative stress |
US9566301B2 (en) | 2012-03-29 | 2017-02-14 | Cxl Ophthalmics, Llc | Compositions and methods for treating or preventing diseases associated with oxidative stress |
US10092594B2 (en) | 2012-03-29 | 2018-10-09 | Cxl Ophthalmics, Llc | Compositions and methods for treating or preventing diseases associated with oxidative stress |
US10575986B2 (en) | 2012-03-29 | 2020-03-03 | Cxl Ophthalmics, Llc | Ophthalmic treatment solution delivery devices and delivery augmentation methods |
EP2830627A4 (en) * | 2012-03-29 | 2015-10-14 | Cxl Ophthalmics Llc | Ocular treatment solutions, delivery devices and delivery augmentation methods |
US9555111B2 (en) | 2012-03-29 | 2017-01-31 | Cxl Ophthalmics, Llc | Ocular cross-linking system and method for sealing corneal wounds |
US9498122B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
US9498114B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
RU2542799C1 (en) * | 2013-10-29 | 2015-02-27 | Игорь Борисович Медведев | Method of treating corneal keratoconus |
US11219553B2 (en) | 2014-10-27 | 2022-01-11 | Avedro, Inc. | Systems and methods for cross-linking treatments of an eye |
US10350111B2 (en) | 2014-10-27 | 2019-07-16 | Avedro, Inc. | Systems and methods for cross-linking treatments of an eye |
US10114205B2 (en) | 2014-11-13 | 2018-10-30 | Avedro, Inc. | Multipass virtually imaged phased array etalon |
US11167149B2 (en) | 2015-04-24 | 2021-11-09 | Avedro, Inc. | Systems and methods for photoactivating a photosensitizer applied to an eye |
US12070618B2 (en) | 2015-04-24 | 2024-08-27 | Avedro, Inc. | Systems and methods for photoactivating a photosensitizer applied to an eye |
US10258809B2 (en) | 2015-04-24 | 2019-04-16 | Avedro, Inc. | Systems and methods for photoactivating a photosensitizer applied to an eye |
US10688196B2 (en) | 2015-04-29 | 2020-06-23 | Sooft Italia Spa | Cross-linking agents of collagen fibers for the use in the treatment of corneal ectasia |
WO2016174688A1 (en) | 2015-04-29 | 2016-11-03 | Sooft Italia Spa | Improved cross-linking agents of collagen fibers for the use in the treatment of corneal ectasia |
US10028657B2 (en) | 2015-05-22 | 2018-07-24 | Avedro, Inc. | Systems and methods for monitoring cross-linking activity for corneal treatments |
US11207410B2 (en) | 2015-07-21 | 2021-12-28 | Avedro, Inc. | Systems and methods for treatments of an eye with a photosensitizer |
CN105256059B (en) * | 2015-11-20 | 2019-01-18 | 山东省眼科研究所 | TUBA3D gene is preparing the application in keratoconus diagnostic product |
CN105256059A (en) * | 2015-11-20 | 2016-01-20 | 山东省眼科研究所 | Application of TUBA3D gene in preparing keratoconus diagnosis product |
US20180236077A1 (en) * | 2017-02-21 | 2018-08-23 | Avedro, Inc. | Formulations for eye treatments |
WO2018156593A1 (en) * | 2017-02-21 | 2018-08-30 | Avedro, Inc. | Formulations for eye treatments |
EP3585393A4 (en) * | 2017-02-21 | 2020-12-30 | Avedro, Inc. | Formulations for eye treatments |
US12042433B2 (en) | 2018-03-05 | 2024-07-23 | Avedro, Inc. | Systems and methods for eye tracking during eye treatment |
US11766356B2 (en) | 2018-03-08 | 2023-09-26 | Avedro, Inc. | Micro-devices for treatment of an eye |
US12016794B2 (en) | 2018-10-09 | 2024-06-25 | Avedro, Inc. | Photoactivation systems and methods for corneal cross-linking treatments |
US11642244B2 (en) | 2019-08-06 | 2023-05-09 | Avedro, Inc. | Photoactivation systems and methods for corneal cross-linking treatments |
Also Published As
Publication number | Publication date |
---|---|
KR20110046567A (en) | 2011-05-04 |
AU2009286285B2 (en) | 2015-03-26 |
ITRM20080472A1 (en) | 2010-02-28 |
IL211448A (en) | 2016-05-31 |
EA023607B1 (en) | 2016-06-30 |
BRPI0910368B1 (en) | 2020-01-28 |
PE20110287A1 (en) | 2011-05-15 |
CN102164592B (en) | 2015-09-23 |
CL2011000378A1 (en) | 2011-06-10 |
DK2323642T3 (en) | 2014-05-05 |
EA201100393A1 (en) | 2011-10-31 |
EA022055B1 (en) | 2015-10-30 |
BRPI0910368B8 (en) | 2021-05-25 |
IL211448A0 (en) | 2011-05-31 |
IT1393402B1 (en) | 2012-04-20 |
JP2012500844A (en) | 2012-01-12 |
PL2323642T3 (en) | 2014-07-31 |
US20110152219A1 (en) | 2011-06-23 |
CN102164592A (en) | 2011-08-24 |
EP2323642A1 (en) | 2011-05-25 |
EP2323642B1 (en) | 2014-02-19 |
PT2323642E (en) | 2014-05-15 |
ES2460578T3 (en) | 2014-05-13 |
MX2011002234A (en) | 2011-04-05 |
EA201300272A1 (en) | 2013-07-30 |
BRPI0910368A2 (en) | 2015-10-13 |
MX358176B (en) | 2018-08-08 |
AU2009286285A1 (en) | 2010-03-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2323642B1 (en) | Use of EDTA+tromethamine or of photoenhancers, associated to riboflavin for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders | |
Sanjay et al. | Herpes zoster ophthalmicus | |
JP5583310B2 (en) | Ophthalmic formulation for prevention and treatment of ocular symptoms | |
JP2009501726A (en) | Ophthalmologically active agent formulations and methods of administration thereof | |
JP2014221841A (en) | OPHTHALMIC FORMULATIONS INCLUDING SELECTIVE α1 ANTAGONISTS | |
KR20140076587A (en) | Compositions and methods for treating presbyopia, mild hyperopia, and irregular astigmatism | |
JP2009501727A (en) | Treatment of conditions associated with the presence of macromolecular assemblies, especially ophthalmic disorders | |
JP2009524692A (en) | Formulations and methods for dry eye | |
US10973758B2 (en) | Methods of eye treatment using therapeutic compositions containing dipyridamole | |
KR102578102B1 (en) | Topical ophthalmic formulations of endothelin receptor antagonists | |
JP6820658B2 (en) | Compositions for use in the treatment of eye diseases with dipyridamole | |
RU2281086C1 (en) | Ophthalmic anti-histaminic drops | |
Muñoz-Negrete et al. | Guidelines for treatment of chronic primary angle-closure glaucoma | |
MXPA05004465A (en) | Use of propionyl l-carnitine for the preparation of a medicament for the treatment of glaucoma. | |
CA2731871C (en) | Use of enhancers, possibly associated to riboflavin, as well as corresponding ophthalmic compositions for corneal cross-linking in the treatment of the keratoconus or of other corneal ectasic disorders | |
KR20210127872A (en) | Formulations comprising a chelating agent, a penetration enhancer and hydroxyethyl cellulose for the treatment of an ophthalmic disease | |
Gupta et al. | In situ gelling system and other possible innovative approach for ocular disease: A review | |
CN116459251A (en) | Ophthalmic preparation containing cevimeline and preparation method and application thereof | |
Swartz et al. | LIPID METABOLISM DISORDERS |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200980138188.3 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 09748494 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2011524534 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011000378 Country of ref document: CL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 000192-2011 Country of ref document: PE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 211448 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/A/2011/002234 Country of ref document: MX |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2009748494 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2009286285 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 201100393 Country of ref document: EA |
|
ENP | Entry into the national phase |
Ref document number: 20117006855 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1280/KOLNP/2011 Country of ref document: IN |
|
ENP | Entry into the national phase |
Ref document number: 2009286285 Country of ref document: AU Date of ref document: 20090827 Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: PI0910368 Country of ref document: BR Kind code of ref document: A2 Effective date: 20110112 |