[go: up one dir, main page]

CN102164592B - 可与核黄素一起使用的增强剂制备用于在圆锥角膜的治疗中进行角膜交联的眼用组合物的用途以及相应眼用组合物 - Google Patents

可与核黄素一起使用的增强剂制备用于在圆锥角膜的治疗中进行角膜交联的眼用组合物的用途以及相应眼用组合物 Download PDF

Info

Publication number
CN102164592B
CN102164592B CN200980138188.3A CN200980138188A CN102164592B CN 102164592 B CN102164592 B CN 102164592B CN 200980138188 A CN200980138188 A CN 200980138188A CN 102164592 B CN102164592 B CN 102164592B
Authority
CN
China
Prior art keywords
riboflavin
corneal
keratoconus
tromethane
ophthalmic compositions
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.)
Active
Application number
CN200980138188.3A
Other languages
English (en)
Other versions
CN102164592A (zh
Inventor
马尔切洛·斯塔尼
爱德华多·斯塔尼
马西莫·菲利佩洛
乔瓦尼·卡瓦洛
欧金尼奥·索多
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fidia Farmaceutici SpA
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40679354&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN102164592(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Sooft Italia SpA filed Critical Sooft Italia SpA
Publication of CN102164592A publication Critical patent/CN102164592A/zh
Application granted granted Critical
Publication of CN102164592B publication Critical patent/CN102164592B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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

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 Containing Plant Substances (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

本文描述的是增强剂(可与核黄素一起使用)用于通过角膜交联法来治疗圆锥角膜或其它扩张性角膜疾病的用途，以及相应组合物。

Description

可与核黄素一起使用的增强剂制备用于在圆锥角膜的治疗中进行角膜交联的眼用组合物的用途以及相应眼用组合物
本发明涉及增强剂用于制备可包含核黄素的眼用组合物(尤其是洗眼剂)的用途，所述眼用组合物被设计用于通过交联而在治疗圆锥角膜或其它的扩张性角膜疾病过程中无需去除角膜上皮(去上皮)的处理即可使组合物被吸收进入角膜基质。同时本发明也涉及用于角膜交联技术的相应的眼用组合物。
圆锥角膜是一种严重的角膜疾病，因为它是一种非炎性进行性营养不良，年发病率约为50/100000，通常为10至20岁的年轻人。圆锥角膜是一种遗传性疾病，在女性中高发，并且有时似乎与内分泌腺体(垂体和甲状腺)的功能障碍有关。在85％的病例中，患者的双眼均可发病，其发展过程可能会因人而异。
该病开始发病时，出现曲率不规则，这改变了角膜的折光能力，从而导致像的扭曲以及远、近视觉的混淆。患者都抱怨视力减退，尤其是远距离视力的减退。视力持续发生不可逆的减退，因此需要频繁地更换眼镜，并因此可能被误认为是伴有散光的近视。
由于该病所导致的角膜基质先天性结构脆弱，几年之后，角膜常常进行性地被磨损并朝顶点方向变薄。之后发生角膜曲率不规则，这使其失去球状外形并呈现出特征性的圆锥形(圆锥角膜)。
使用生物显微镜可以观察到圆锥角膜顶端处角膜厚度的明显变薄。随着时间的进展，圆锥角膜的顶端变得不透光，这是因为该部分角膜的营养状况发生改变，在最严重的情况下可以出现超过62D的角膜曲率，而角膜的厚度甚至能够达到446μm。
如果该疾病被忽视的话，则顶端可发生溃疡，随之发生角膜穿孔，并出现疼痛、流泪和眼睑痉挛。这些因圆锥角膜而引发的角膜改变导致角膜蛋白质分布的改变，导致微小的瘢痕，其进一步扭曲视觉图像，在一些病例中还会阻止光的通过，因而产生令人烦恼的眩晕感，尤其是在一天中太阳在地平线上位置较低的时候(日出和日落时)。
正如上文所提到的，为了矫正视力，就必须频繁地更换眼镜。只有在 已证明使用眼镜无法取得满意效果后，在较轻微的情况下可以使用刚性的隐形眼镜。
当患圆锥角膜的角膜发生显著变薄时，或者如果在角膜表面撕裂之后形成瘢痕时，就会出现严重的问题，甚至有必要进行角膜移植(角膜移植术)。
2002年，所谓的板层角膜移植术被引入意大利用于治疗圆锥角膜。其中实际上并没有替换整个角膜，而是仅替换外层，即患病的部分。
然而，在德国Dresda的Carl Gustaw Carus大学的眼科诊所中，1997年已经开发出了一种更加安全的并且介入性较小的新技术，被称为“角膜交联(corneal cross-linking)”，这种技术具体使用被紫外激光激发的核黄素；2005年，这一技术也在意大利进行了测试，到现在为止，该技术已经成功地在意大利的许多眼科诊所中广泛使用。
角膜交联是一种低侵入性的方法，其使用被紫外激光(366nm)激发的核黄素；该方法是无痛的，并且可以在日间医院中进行。这种交联通过交织和提高角膜胶原蛋白纤维之间的联系(交联)而使得患圆锥角膜的角膜的结构得以增强。已经进行的临床研究证明，该方法能够减少与圆锥角膜相关的散光，并能够减缓或者阻止圆锥角膜的发展，从而避免进行角膜移植。其它以角膜扩张为特征的疾病也可受益于使用交联法进行的治疗。
角膜交联通过进行角膜局部麻醉以磨除直径为8-9mm的角膜上皮(去上皮)来进行。之后，频繁地滴入基于核黄素的0.1％眼用溶液，15分钟之后，用紫外光(UV-A)发光器照射5分钟；之后再重新滴入，然后再重新照射，总共进行6个循环(共30分钟)。
常用于角膜交联的核黄素(尤其是磷酸核黄素)是一种亲水性、光敏化的和光聚合的分子，透过上皮的能力差，因而到达角膜基质的能力也差。因此，有必要在开始UV-A照射前通过去除角膜上皮(去上皮)来促进其吸收和角膜的完全吸入。这一过程可能(尽管很少见)在角膜水平引发并发症、疼痛，此外，这也是一种使得眼科医生更难完成任务的方法。
因此，很期望无需去除角膜上皮就可以改善核黄素的吸收，从而获得一种非侵入性的角膜交联，无需或减少麻醉，并且可以迅速愈合而没有疼痛或可能的并发症。
更加理想的是，设想某些化合物可以易于实现上皮吸收，而在使胶原纤维光敏化和光聚合方面又具有与核黄素相同或更高的活性；所述化合物 应该优选地以与可见光接近的光强度所激发，这样就可以避免激活核黄素所需的紫外光重复照射所产生的有害作用。
我们意想不到地发现，通过向角膜施用含有增强剂(可与核黄素一起使用)的眼用组合物，获得了改善的角膜交联，这通过以接近可见光(害处更小)的照射进行激发而无需进行去上皮来实现，所述增强剂选自：
生物增强剂(即这样的物质，其促进核黄素或其它光敏化和光聚合物质透过角膜上皮，使其被角膜基质本身所吸收)，例如，EDTA、EDTA钠、EDTA钾、聚山梨醇酯80、氨基丁三醇、氮酮、氯化苯甲烃铵、西吡氯铵、十六烷基三甲基氯化铵、月桂酸、薄荷醇、甲氧基水杨酸、聚氧乙烯、甘氨胆酸钠、甘氨脱氧胆酸钠、十二烷基硫酸钠、水杨酸钠、牛磺胆酸钠、牛磺脱氧胆酸钠；和/或
光增强剂(即光敏化和光聚合物质，其可以很容易地被上皮所吸收，并且像核黄素一样能够被光激活而形成角膜交联)，例如，染料吖啶黄、奎尼丁黄、亚甲蓝和赤藓红，这些化合物的结构如下：
吖啶黄：
可用吸收：460nm
奎尼丁黄
亚甲蓝
可用吸收：668nm
赤藓红B
2′，4′，5′，7′-四碘荧光素二钠盐
吸收：525nm
分子式：
C20H6I4Na2O5
分子量：
879.86
因此，本发明考虑上述增强剂(单独使用或是多种混合使用，并可与核黄素一起使用)用于制备眼用组合物的用途，所述眼用组合物用于在圆锥角膜或其它角膜扩张中进行交联。
本发明的增强剂可以直接施用于角膜以用于圆锥角膜或其它角膜扩张中的角膜交联，而没有已证实的细胞毒性。
本发明的另外一个主题是包含上述增强剂(可与核黄素一起使用)的眼用组合物，所述眼用组合物可以根据已知的技术来制备，并可具体包含：
-一种或多种生物增强剂和一种或多种光增强剂，还可包含核黄素；
-一种或多种生物增强剂，还可包含核黄素；
-一种或多种光增强剂，还可包含核黄素。
在眼部施用上述包含一种或多种生物增强剂或者一种或多种光增强剂的组合物之后，可以直接在角膜上施用一种或多种光敏化和光聚合物质(尤其是核黄素)的溶液。
本发明的生物增强剂在上述所有组合物中都以合适的量存在，其选自重量百分比0.001％至5％(相对于组合物)。
特别地，增强剂的能力尤其依赖于EDTA和氨基丁三醇的联合，因为这两种化合物一起在EDTA的未成盐羧基和氨基丁三醇之间形成离子对，该离子对具备显著的膜穿透能力。
在这些研究结果中，值得提到的是：如果氨基丁三醇优选地以0.05wt％至0.5wt％存在，且EDTA优选地以0.05wt％至0.5wt％存在，则核黄素的吸收立即发生。
本发明的光敏化和光聚合物质(光增强剂，其中包括核黄素)以合适的量使用，其选自0.001wt％至1wt％(相对于组合物)
此外，优选用于本发明中的核黄素是磷酸核黄素，在上述所有组合物中均为合适的量，优选为本发明组合物的0.05wt％至0.3wt％。
本发明的眼用组合物可制备成洗眼剂、滴眼液、洗眼液、软膏剂的形式，以及能够根据已知技术进行角膜应用的任何药物形式，下文中以举例的方式提供相关的实施例，这些实施例并不意味着是对发明进行任何的限制。
在每个实施例中，每一种组分的剂量均以重量百分比的形式表示。
实施例1
实施例2
实施例3
实施例4
实施例5
实施例6
实施例7
实施例8
实施例9
注意，当氨基丁三醇浓度提高时，需要充分增加磷酸二氢钠，以保证pH值为7-7.2。
实施例10
实施例11
实施例12
实施例13
需要指出的是，配方1-13也可以通过加入足量的氯化钠(或其它渗透溶质)而制成等渗或甚至高渗的溶液以达到所述目的。

Claims (6)

1.与氨基丁三醇联合的EDTA、与氨基丁三醇联合的EDTA钠和与氨基丁三醇联合的EDTA钾，单独使用或混合在一起使用，用于制备眼用组合物的用途，所述眼用组合物用于在圆锥角膜的治疗中进行角膜交联的方法，其中所述组合物包含核黄素或磷酸核黄素。
2.根据权利要求1的用途，其中与氨基丁三醇联合的EDTA钠和与氨基丁三醇联合的EDTA钾以相对于所述组合物为0.0001-5wt％的量存在。
3.根据权利要求2的用途，EDTA为0.001到1wt％，氨基丁三醇为0.001到2wt％。
4.根据权利要求3的用途，其中EDTA以0.05到0.5wt％的量存在和/或氨基丁三醇以0.05到0.5wt％的量存在。
5.根据权利要求1的用途，其中磷酸核黄素以0.05至0.3wt％的量存在。
6.用于圆锥角膜的治疗中进行角膜交联之方法的组合物，其中存在与氨基丁三醇联合的EDTA、与氨基丁三醇联合的EDTA钠和与氨基丁三醇联合的EDTA钾，还可存在核黄素。
CN200980138188.3A 2008-08-28 2009-08-27 可与核黄素一起使用的增强剂制备用于在圆锥角膜的治疗中进行角膜交联的眼用组合物的用途以及相应眼用组合物 Active CN102164592B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ITRM2008A000472 2008-08-28
ITRM2008A000472A IT1393402B1 (it) 2008-08-28 2008-08-28 Uso di enhancer eventualmente con riboflavina, nonche' relative composizioni oftalmiche per cross-linking corneale del cheratocono o di altre patologie ectasiche corneali
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

Publications (2)

Publication Number Publication Date
CN102164592A CN102164592A (zh) 2011-08-24
CN102164592B true CN102164592B (zh) 2015-09-23

Family

ID=40679354

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200980138188.3A Active CN102164592B (zh) 2008-08-28 2009-08-27 可与核黄素一起使用的增强剂制备用于在圆锥角膜的治疗中进行角膜交联的眼用组合物的用途以及相应眼用组合物

Country Status (18)

Country Link
US (1) US20110152219A1 (zh)
EP (1) EP2323642B1 (zh)
JP (1) JP2012500844A (zh)
KR (1) KR20110046567A (zh)
CN (1) CN102164592B (zh)
AU (1) AU2009286285B2 (zh)
BR (1) BRPI0910368B8 (zh)
CL (1) CL2011000378A1 (zh)
DK (1) DK2323642T3 (zh)
EA (2) EA023607B1 (zh)
ES (1) ES2460578T3 (zh)
IL (1) IL211448A (zh)
IT (1) IT1393402B1 (zh)
MX (2) MX2011002234A (zh)
PE (1) PE20110287A1 (zh)
PL (1) PL2323642T3 (zh)
PT (1) PT2323642E (zh)
WO (1) WO2010023705A1 (zh)

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2227197A4 (en) 2007-12-05 2011-06-22 Avedro Inc EYE THERAPY SYSTEM
US8366689B2 (en) 2008-09-30 2013-02-05 Avedro, Inc. Method for making structural changes in corneal fibrils
WO2011050164A1 (en) 2009-10-21 2011-04-28 Avedro, Inc. Eye therapy
JP6377906B2 (ja) 2010-03-19 2018-08-22 アヴェドロ・インコーポレーテッドＡｖｅｄｒｏ，Ｉｎｃ． 眼治療を適用およびモニターするためのシステム
US20110280763A1 (en) * 2010-05-17 2011-11-17 Abbott Medical Optics Inc. Light-activated disinfection system
IT1400982B1 (it) 2010-07-05 2013-07-05 Pinelli Collirio osmotico trans-epiteliale per la cura del cheratocono.
US9622911B2 (en) 2010-09-30 2017-04-18 Cxl Ophthalmics, Llc Ophthalmic treatment device, system, and method of use
EP2663281B1 (en) 2011-01-12 2016-08-10 Sooft Italia Spa Corneal delivery of cross-linking agents by iontophoresis for the treatment of keratoconus and related ophthalmic compositions
ES2539717T3 (es) 2011-01-12 2015-07-03 Sooft Italia S.P.A. Dispositivo para la administración corneal de rivoflavina mediante iontoforesis para el tratamiento de queratocono
WO2012158991A2 (en) * 2011-05-18 2012-11-22 Avedro, Inc. Controlled application of cross-linking agent
WO2012162529A1 (en) 2011-05-24 2012-11-29 Avedro, Inc. Systems and methods for reshaping an eye feature
WO2012167260A2 (en) 2011-06-02 2012-12-06 Avedro, Inc. Systems and methods for monitoring time based photo active agent delivery or photo active marker presence
ITRM20110560A1 (it) * 2011-10-25 2013-04-26 Sooft Italia Spa Migliorata composizione di cross-linking per il trattamento del cheratocono mediante iontoforesi
RU2481809C1 (ru) * 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" Способ лечения кератэктазии после лазик
EP2830554A1 (en) 2012-03-29 2015-02-04 CXL Ophthalmics, LLC Ocular cross-linking system and method for sealing corneal wounds
WO2013148896A1 (en) 2012-03-29 2013-10-03 Cxl Ophthalmics, Llc Ocular treatment solutions, delivery devices and delivery augmentation methods
US9566301B2 (en) 2012-03-29 2017-02-14 Cxl Ophthalmics, Llc Compositions and methods for treating or preventing diseases associated with oxidative stress
RU2487691C1 (ru) * 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 Способ лечения кератоконуса
WO2013059837A2 (en) 2012-07-16 2013-04-25 Avedro, Inc. Systems and methods for corneal cross-linking with pulsed light
KR102002634B1 (ko) * 2013-01-28 2019-07-22 노바르티스 아게 각막 교차 결합을 위한 장치
WO2014189849A1 (en) * 2013-05-19 2014-11-27 Avedro, Inc. Systems, methods, and compositions for cross-linking
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 (ru) * 2013-10-29 2015-02-27 Игорь Борисович Медведев Способ лечения кератоконуса роговицы
US9931199B2 (en) * 2014-05-05 2018-04-03 Roberto Gustavo ALBERTAZZI Methods and apparatus for treating keratoconus
US11338059B2 (en) 2014-05-12 2022-05-24 Gholam A. Peyman Method of corneal and scleral inlay crosslinking and preservation
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
US12396889B2 (en) 2014-05-12 2025-08-26 Gholam A. Peyman Lamellar corneal autologous or homologous graft in refractive surgery
US9427355B1 (en) * 2014-05-12 2016-08-30 Gholam A. Peyman Corneal transplantation with a cross-linked cornea
US11259914B2 (en) 2014-05-12 2022-03-01 Gholam A. Peyman Molding or 3-D printing of a synthetic refractive corneal lenslet
US10206569B1 (en) 2014-05-12 2019-02-19 Gholam A. Peyman Corneal intraocular pressure sensor and a surgical 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
US9744029B1 (en) 2014-05-12 2017-08-29 Gholam A. Peyman Method of preventing capsular opacification and fibrosis utilizing an accommodative intraocular lens implant
US10314690B1 (en) 2014-05-12 2019-06-11 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
US10583221B2 (en) 2014-05-12 2020-03-10 Gholam A. Peyman Method of corneal transplantation or corneal inlay implantation with cross-linking
US9937033B1 (en) 2014-05-12 2018-04-10 Gholam A. Peyman Corneal lenslet implantation with a cross-linked cornea
US10881503B2 (en) 2014-05-12 2021-01-05 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
US10709546B2 (en) 2014-05-12 2020-07-14 Gholam A. Peyman Intracorneal lens implantation 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
US12383393B2 (en) 2014-05-12 2025-08-12 Gholam A. Peyman Ablatable corneal inlay for correction of refractive errors and/or presbyopia
CN107205845B (zh) 2014-10-27 2020-03-31 艾维德洛公司 用于眼的交联治疗的系统和方法
WO2016077747A1 (en) 2014-11-13 2016-05-19 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
PL3288588T3 (pl) 2015-04-29 2019-02-28 Sooft Italia S.P.A. Ulepszone środki sieciujące włókna kolagenowe do stosowania w leczeniu ektazji rogówki
US10028657B2 (en) 2015-05-22 2018-07-24 Avedro, Inc. Systems and methods for monitoring cross-linking activity for corneal treatments
CN116832158A (zh) 2015-07-21 2023-10-03 艾维德洛公司 用光敏剂治疗眼睛的系统和方法
CN105256059B (zh) * 2015-11-20 2019-01-18 山东省眼科研究所 Tuba3d基因在制备圆锥角膜诊断制品中的应用
ITUB20160237A1 (it) * 2016-01-26 2017-07-26 Vision Engineering Italy Soc A Responsabilita Limitata Apparato di controllo del dosaggio di un agente cromoforo in un tessuto corneale e procedimento per dosare un agente cromoforo in un tessuto corneale
WO2017180851A1 (en) 2016-04-13 2017-10-19 Avedro, Inc. Systems and methods for delivering drugs to an eye
WO2018156593A1 (en) 2017-02-21 2018-08-30 Avedro, Inc. Formulations for eye treatments
JP7379357B2 (ja) 2018-03-05 2023-11-14 アヴェドロ・インコーポレーテッド 眼の治療中の眼球追跡用システム
US11766356B2 (en) 2018-03-08 2023-09-26 Avedro, Inc. Micro-devices for treatment of an eye
WO2020061274A1 (en) 2018-09-19 2020-03-26 Avedro, Inc. Systems and methods for eye tracking during eye treatment
CN113329723A (zh) 2018-09-19 2021-08-31 艾维德洛公司 治疗角膜扩张型疾病的系统和方法
EP3863576A4 (en) 2018-10-09 2022-07-06 Avedro, Inc. PHOTOACTIVATION SYSTEMS AND METHODS FOR CORNEAL CROSSLINKING TREATMENT
US12171691B2 (en) 2019-02-26 2024-12-24 Avedro, Inc. Systems and methods for cross-linking treatments of an eye
US12226478B2 (en) 2019-04-28 2025-02-18 Gholam A. Peyman Method of treating, reducing, or alleviating a medical condition in a patient
US11707518B2 (en) 2019-04-28 2023-07-25 Gholam A. Peyman Method of treating, reducing, or alleviating a medical condition in a patient
WO2021026405A1 (en) 2019-08-06 2021-02-11 Avedro, Inc. Photoactivation systems and methods for corneal cross-linking treatments
CN110314034B (zh) * 2019-08-08 2021-12-03 南京市第一医院 一种可实现个性治疗的角膜交联装置
WO2022103775A1 (en) 2020-11-12 2022-05-19 Singletto Inc. Microbial disinfection for personal protection equipment
WO2022192237A1 (en) 2021-03-08 2022-09-15 Avedro, Inc. Systems and methods for generating patient-specific corneal cross-linking treatment patterns
CN115177729B (zh) * 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) 肾上腺素受体激动剂在制备圆锥角膜交联促渗剂中的应用
US12359369B2 (en) 2022-08-11 2025-07-15 Singletto Inc. Skin protection against microbial particles

Citations (1)

* Cited by examiner, † Cited by third party
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

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
CN1200698C (zh) * 1998-03-09 2005-05-11 伊斯塔药品公司 角膜硬化剂在制备治疗眼睛屈光不正的药物中的用途
US6174524B1 (en) 1999-03-26 2001-01-16 Alcon Laboratories, Inc. Gelling ophthalmic compositions containing xanthan gum
US7331350B2 (en) * 2000-02-11 2008-02-19 The General Hospital Corporation Photochemical tissue bonding
ITRM20050443A1 (it) * 2005-08-12 2007-02-13 Opocrin Spa Preparati oftalmici a base di polisaccaridi mucoadesivi con capacita' riepitelizzante della 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

Patent Citations (1)

* Cited by examiner, † Cited by third party
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

Also Published As

Publication number Publication date
DK2323642T3 (da) 2014-05-05
US20110152219A1 (en) 2011-06-23
EP2323642A1 (en) 2011-05-25
BRPI0910368B1 (pt) 2020-01-28
PE20110287A1 (es) 2011-05-15
IT1393402B1 (it) 2012-04-20
AU2009286285B2 (en) 2015-03-26
MX2011002234A (es) 2011-04-05
AU2009286285A1 (en) 2010-03-04
WO2010023705A1 (en) 2010-03-04
IL211448A (en) 2016-05-31
EA201300272A1 (ru) 2013-07-30
EA201100393A1 (ru) 2011-10-31
EP2323642B1 (en) 2014-02-19
PT2323642E (pt) 2014-05-15
KR20110046567A (ko) 2011-05-04
BRPI0910368B8 (pt) 2021-05-25
PL2323642T3 (pl) 2014-07-31
CN102164592A (zh) 2011-08-24
ES2460578T3 (es) 2014-05-13
ITRM20080472A1 (it) 2010-02-28
EA023607B1 (ru) 2016-06-30
BRPI0910368A2 (pt) 2015-10-13
MX358176B (es) 2018-08-08
JP2012500844A (ja) 2012-01-12
EA022055B1 (ru) 2015-10-30
CL2011000378A1 (es) 2011-06-10
IL211448A0 (en) 2011-05-31

Similar Documents

Publication Publication Date Title
CN102164592B (zh) 可与核黄素一起使用的增强剂制备用于在圆锥角膜的治疗中进行角膜交联的眼用组合物的用途以及相应眼用组合物
CN1753683B (zh) 预防和治疗不良眼部病症的眼用制剂
ES2590127T3 (es) Administración corneal de agentes de entrecruzamiento por iontoforesis para el tratamiento de queratocono y composiciones oftálmicas relacionadas
JP7655988B2 (ja) 近視進行の治療
JP2020530470A (ja) 老化細胞を排除する薬学的作用物質を用いる、黄斑変性症、緑内障、および糖尿病性網膜症などの眼病態の治療
JP2002506013A (ja) 酵素角膜矯正術における角膜硬化剤の使用
JP2009501726A (ja) 眼科学的活性剤の製剤とその投与の方法
EP4279063A2 (en) Ophthalmic pharmaceutical composition, preparation method therefor and application thereof
WO2005030221A1 (ja) 加齢黄斑変性治療剤
Barbosa et al. Effect of cross-linking on corneal thickness in patients with corneal edema
CN105142670B (zh) 用于治疗眼部炎性疾病的滴眼剂组合物及其制备方法
Kollias et al. Phototherapeutic keratectomy in children
JP2022547401A (ja) 翼状片に関連した眼の見た目についての心配を軽減するための方法
CN116270442B (zh) 一种用于矫正近距离视力的眼用制剂
US20250295631A1 (en) Novel treatment
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
JPH08325143A (ja) 角膜実質損傷治療剤
Assouline March consultation# 4
HK40066668A (zh) 在假晶状体患者中使用拟副交感神经药物单独或与一种或多种α激动剂组合以产生多焦点
Walker The effect of Xylocaine Hydrodissection on posterior capsule opacification after cataract surgery
DuBosar Researchers attempt to progress cross-linking in the US.
SUTPHIN Corneal Crosslinking with Riboflavin and Ultraviolet A. Part II. Clinical Indications and Results
Walker A thesis submitted for the degree of Master of Philosophy (Surgery) of the Australian National University
JP2009249289A (ja) 視機能障害の予防または治療剤

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20220616

Address after: No. 3/a, factory Bridge Street, atano Terme, Italy

Patentee after: FIDIA FARMACEUTICI S.P.A.

Address before: Italy, Ascoli Piceno

Patentee before: SOOFT ITALIA S.P.A.

TR01 Transfer of patent right