WO2009001396A1 - Solution oculaire stérile jetable pour une réticulation cornéenne d'un kératocône, et son procédé de fabrication - Google Patents

Solution oculaire stérile jetable pour une réticulation cornéenne d'un kératocône, et son procédé de fabrication Download PDF

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Publication number
WO2009001396A1
WO2009001396A1 PCT/IT2008/000430 IT2008000430W WO2009001396A1 WO 2009001396 A1 WO2009001396 A1 WO 2009001396A1 IT 2008000430 W IT2008000430 W IT 2008000430W WO 2009001396 A1 WO2009001396 A1 WO 2009001396A1
Authority
WO
WIPO (PCT)
Prior art keywords
linking
solution according
corneal cross
keratoconus
ocular
Prior art date
Application number
PCT/IT2008/000430
Other languages
English (en)
Inventor
Eugenio Sodo
Giovanni Cavallo
Marcello Stagni
Original Assignee
Sooft Italia Spa
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sooft Italia Spa filed Critical Sooft Italia Spa
Publication of WO2009001396A1 publication Critical patent/WO2009001396A1/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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

Definitions

  • the present invention relates to a disposable sterile ocular solution containing riboflavin phosphate
  • vitamin B2 vitamin B2
  • dextran as well as a process for its production and use in the technique of corneal cross-
  • Keratoconus is a rare disease of the cornea, a progressive non-inflammatory dystrophy that each year afflicts approximately 50 persons every 100 000, both men and women, generally of young age, i.e., between 20
  • Keratoconus This disease has a greater frequency in the female sex and is of genetic origin even though it sometimes appears to be correlated to possible dysfunctions of endocrine glands (pituitary and thyroid) . Keratoconus
  • the apex of the cone becomes opaque- on account of an alteration in the nutriment of this part of the cornea. If the disease is neglected, the apex undergoes ulceration with consequent perforation of the cornea; this is accompanied by pain, lacrimation and spasm of the eyelids.
  • Corneal cross-linking is a method that uses UV lasers, is painless and is carried out in a day- hospital. It enables reinforcement of the structure of the cornea affected by keratoconus through the intertwining and increase of the bonds between the fibres of the corneal collagen (cross-linking) . From the first studies conducted, this technique has proven capable of reducing astigmatism, slowing down and at times even temporarily halting the evolution of keratoconus, thus avoiding corneal grafting.
  • the photosensitive solution Under irradiation the photosensitive solution, owing to an "aggregating" effect, generates cross- linking of the corneal lamellae (the layers that make up the surface of the cornea) only where this is necessary, without damaging the cells surrounding the retina. Said reinforcement of the bonds in the corneal collagen induces a hardening of the cornea.
  • the first studies of the technique described above have demonstrated that it is possible to block evolution of the disease and, in many cases, there is noted a decrease in the curvature of the cornea (2 dioptres on average) .
  • the effects of the treatment have a duration of 4-5 years, after which it may be necessary to repeat the intervention.
  • the eye is medicated with eye lotions or antibiotic ointments and closed for some days (3-4 on average) with a bandage or a therapeutic contact lens so as to enable re-formation of the epithelium.
  • the cross-linking ocular solution with a base of dextran and riboflavin phosphate is prepared, in an extemporary and non-sterile way, shortly before use to prevent deterioration of riboflavin in aqueous solution; this leads to an increased danger of infection at the ocular level and a considerable operative difficulty, as well as waste of time, even though the albeit simple operations of dispersion in physiological solution of the polymer (dextran) , solubilization of riboflavin phosphate, and instillation of the preparation on the ocular surface are performed in a suitable environment and by highly qualified operators.
  • the present invention relates to a disposable single-use sterile ocular solution containing riboflavin phosphate (vitamin B2), as well as a process for its production and its use in the corneal cross- linking treatment of keratoconus.
  • the solution according to the present invention is thus safer from the hygiene-health standpoint and far more practical and rapid for its administration to the patient via ocular instillation.
  • the subject of the present invention is a disposable sterile ocular solution containing approximately 20% w/w of dextran and approximately 0.05-0.25% w/w of riboflavin phosphate with appropriate excipients for the corneal cross- linking treatment of keratoconus .
  • a disposable sterile ocular solution containing approximately 0.125% w/w of riboflavin phosphate for the corneal cross-linking treatment of keratoconus.
  • the solution can in fact contain all the excipients envisaged in the art for ocular solutions.
  • the dextran used was Dextran T500 (Pharmacosmos, Denmark) .
  • Another subject of the present invention is in fact a process of production for rendering microbiologically safe the ocular solution that is previously prepared with processes known to the art and treated with a vapour flow at 121°C at a pressure of
  • the pH can stabilize the ocular solution of the present invention, and in particular it is preferable for said ocular solution to have a slightly acidic pH (pH 5.6-5.9), i.e., such as to enable maintenance of a high titre expressed in % w/w of riboflavin phosphate in the sterile aqueous solution.
  • a slightly acidic pH pH 5.6-5.9
  • a slightly acidic pH also using, for example, appropriate amounts of a buffer chosen between monobasic sodium phosphate dihydrate/dibasic sodium phosphate dihydrate or boric acid/sodium tetraborate.
  • the photosensitive preparation of riboflavin phosphate and dextran is instilled on the surface of the cornea; after 5 min, the ocular surface is irradiated for 30 min by UVA rays having a wavelength of 370 nm at a distance of 1 cm from the apex of the cornea.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention porte sur une solution oculaire stérile jetable contenant du phosphate de riboflavine (vitamine B2) et du dextrane, ainsi que sur un procédé pour sa production stérile à l'aide d'un autoclave à 121°C pendant 30 minutes à une pression de 1 atm, pour une utilisation dans le traitement par réticulation cornéenne d'un kératocône.
PCT/IT2008/000430 2007-06-26 2008-06-26 Solution oculaire stérile jetable pour une réticulation cornéenne d'un kératocône, et son procédé de fabrication WO2009001396A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT000356A ITRM20070356A1 (it) 2007-06-26 2007-06-26 Soluzione oculare sterile monouso e suo procedimento di produzione per il cross linking corneale del cheratocono
ITRM2007A000356 2007-06-26

Publications (1)

Publication Number Publication Date
WO2009001396A1 true WO2009001396A1 (fr) 2008-12-31

Family

ID=39885264

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IT2008/000430 WO2009001396A1 (fr) 2007-06-26 2008-06-26 Solution oculaire stérile jetable pour une réticulation cornéenne d'un kératocône, et son procédé de fabrication

Country Status (2)

Country Link
IT (1) ITRM20070356A1 (fr)
WO (1) WO2009001396A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITVA20090052A1 (it) * 2009-07-27 2011-01-28 Ciro Caruso Composizione per il trattamento del cheratocono con tecnica di cross-linking trans-epiteliale o per proteggere strutture interne del globo oculare da raggi uv-a
WO2011012557A1 (fr) * 2009-07-27 2011-02-03 Sanseverino, Renato Solution ophtalmique utilisée pour protéger les structures internes du globe oculaire contre les uv-a ou dans le cadre du traitement du kératocône faisant appel à une technique de réticulation trans-épithéliale
ITVA20100044A1 (it) * 2010-05-20 2011-11-21 Ciro Caruso Soluzione oftalmica per proteggere strutture interne del globo oculare da raggi uv-a o per il trattamento del cheratocono con tecnica di cross-linking trans-epiteliale
WO2012095877A1 (fr) 2011-01-12 2012-07-19 Sooft Italia Spa Administration à la cornée d'agents de réticulation par ionophorèse pour le traitement de kératocône et compositions ophtalmologiques associées
ITRM20110560A1 (it) * 2011-10-25 2013-04-26 Sooft Italia Spa Migliorata composizione di cross-linking per il trattamento del cheratocono mediante iontoforesi
ITRM20130248A1 (it) * 2013-04-24 2014-10-25 Medivis S R L Formulazioni di riboflavina per il cross-linking transepiteliale.
RU2552318C1 (ru) * 2014-03-25 2015-06-10 Государственное бюджетное учреждение "Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан" Препарат для диагностики травм и заболеваний роговицы глаза
EP2830627A4 (fr) * 2012-03-29 2015-10-14 Cxl Ophthalmics Llc Solutions de traitement oculaire, dispositifs d'administration et procédés améliorant l'administration
WO2016174688A1 (fr) 2015-04-29 2016-11-03 Sooft Italia Spa Agents de réticulation améliorés de fibres de collagène à utiliser dans le traitement de la kératectasie
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
US10342697B2 (en) 2016-04-13 2019-07-09 Avedro, Inc. Systems and methods for delivering drugs to an eye

Non-Patent Citations (5)

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Title
ANONYMOUS: "Regolamento dell' Arcispedale di S.M.Nuova.", 12 June 2007 (2007-06-12), XP002502746, Retrieved from the Internet <URL:http://www.sifoweb.it/eventi/rimini2007/pdf/101007_Tendi.pdf> [retrieved on 20081106] *
CAPOROSSI ET AL: "Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen", JOURNAL CATARACT AND REFRACTIVE SURGERY, SURGERY, FAIRFAX, VA, vol. 32, no. 5, 1 May 2006 (2006-05-01), pages 837 - 845, XP005488902, ISSN: 0886-3350 *
EDOARDO STAGNI: "Riboflavin Ophthalmic Medical Device", INTERNET ARTICLE, 2 February 2007 (2007-02-02), XP002502745, Retrieved from the Internet <URL:http://www.assocheratocono.org/public2/documenti/Riboflavin.pdf> [retrieved on 20081106] *
LAMBERT W E ET AL: "Liquid-chromatographic measurement of riboflavin in serum and urine with isoriboflavin as internal standard.", CLINICAL CHEMISTRY AUG 1985, vol. 31, no. 8, August 1985 (1985-08-01), pages 1371 - 1373, XP002502747, ISSN: 0009-9147 *
WOLLENSAK GREGOR ET AL: "Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus", AMERICAN JOURNAL OF OPHTHALMOLOGY,, vol. 135, no. 5, 1 May 2003 (2003-05-01), pages 620 - 627, XP002496965 *

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2540481C2 (ru) * 2009-07-27 2015-02-10 Сальваторе Троизи Офтальмологический раствор для защиты внутренних структур глазного яблока от уф-а лучей или для лечения кератоконуса методом трансэпителиального кросс-линкинга
WO2011012557A1 (fr) * 2009-07-27 2011-02-03 Sanseverino, Renato Solution ophtalmique utilisée pour protéger les structures internes du globe oculaire contre les uv-a ou dans le cadre du traitement du kératocône faisant appel à une technique de réticulation trans-épithéliale
CN102470120A (zh) * 2009-07-27 2012-05-23 雷纳托·圣塞韦里诺 用于保护眼球的内部结构抵抗紫外线或用于用跨上皮交联技术治疗圆锥角膜的眼用溶液
JP2013500302A (ja) * 2009-07-27 2013-01-07 サンセベリノ，レナト Ｕｖ−ａ線に対する眼球内部構造保護用又は経上皮架橋術式による円錐角膜の治療用点眼液
ITVA20090052A1 (it) * 2009-07-27 2011-01-28 Ciro Caruso Composizione per il trattamento del cheratocono con tecnica di cross-linking trans-epiteliale o per proteggere strutture interne del globo oculare da raggi uv-a
US9192594B2 (en) 2009-07-27 2015-11-24 Renato Sanseverino Ophthalmic solution for protecting internal structures of the eyeball against UV-A rays or for the treatment of keratoconus with a trans-epithelial cross-linking technique
ITVA20100044A1 (it) * 2010-05-20 2011-11-21 Ciro Caruso Soluzione oftalmica per proteggere strutture interne del globo oculare da raggi uv-a o per il trattamento del cheratocono con tecnica di cross-linking trans-epiteliale
US11135090B2 (en) 2010-09-30 2021-10-05 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
US10285857B2 (en) 2010-09-30 2019-05-14 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
CN103384514A (zh) * 2011-01-12 2013-11-06 索夫特意大利公司 通过离子透入法角膜递送交联剂治疗圆锥形角膜及与之相关的眼药组合物
WO2012095877A1 (fr) 2011-01-12 2012-07-19 Sooft Italia Spa Administration à la cornée d'agents de réticulation par ionophorèse pour le traitement de kératocône et compositions ophtalmologiques associées
EA026703B1 (ru) * 2011-10-25 2017-05-31 Соофт Италия Спа Рибофлавин-содержащая офтальмологическая композиция, вводимая посредством ионтофореза, пригодная для лечения кератоконуса
ITRM20110560A1 (it) * 2011-10-25 2013-04-26 Sooft Italia Spa Migliorata composizione di cross-linking per il trattamento del cheratocono mediante iontoforesi
WO2013061350A1 (fr) * 2011-10-25 2013-05-02 Sooft Italia Spa Composition de réticulation améliorée administrée par ionophorèse, utile pour le traitement du kératocône
AU2012327916B2 (en) * 2011-10-25 2016-04-21 Sooft Italia Spa Improved cross-linking 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
CN104023706A (zh) * 2011-10-25 2014-09-03 索夫特意大利公司 用于圆锥形角膜治疗的由离子透入法递送的改良的交联组合物
US10092594B2 (en) 2012-03-29 2018-10-09 Cxl Ophthalmics, Llc Compositions and methods for treating or preventing diseases associated with oxidative stress
US9555111B2 (en) 2012-03-29 2017-01-31 Cxl Ophthalmics, Llc Ocular cross-linking system and method for sealing corneal wounds
US11931291B2 (en) 2012-03-29 2024-03-19 Epion Therapeutics, Inc. Ophthalmic treatment solution delivery devices and delivery augmentation methods
EP2830627A4 (fr) * 2012-03-29 2015-10-14 Cxl Ophthalmics Llc Solutions de traitement oculaire, dispositifs d'administration et procédés améliorant l'administration
US9566301B2 (en) 2012-03-29 2017-02-14 Cxl Ophthalmics, Llc Compositions and methods for treating or preventing diseases associated with oxidative stress
US11497766B2 (en) 2012-03-29 2022-11-15 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
US10729716B2 (en) 2012-03-29 2020-08-04 Cxl Ophthalmics, Llc Compositions and methods for treating or preventing diseases associated with oxidative stress
ITRM20130248A1 (it) * 2013-04-24 2014-10-25 Medivis S R L Formulazioni di riboflavina per il cross-linking transepiteliale.
WO2014174544A1 (fr) * 2013-04-24 2014-10-30 Medivis S.R.L. Formulations de riboflavine pour la réticulation trans-épithéliale
RU2552318C1 (ru) * 2014-03-25 2015-06-10 Государственное бюджетное учреждение "Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан" Препарат для диагностики травм и заболеваний роговицы глаза
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 (fr) 2015-04-29 2016-11-03 Sooft Italia Spa Agents de réticulation améliorés de fibres de collagène à utiliser dans le traitement de la kératectasie
US10342697B2 (en) 2016-04-13 2019-07-09 Avedro, Inc. Systems and methods for delivering drugs to an eye

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