Carbonic anhydrase inhibitors: Synthesis of water soluble sulfonamides incorporating a 4-sulfamoylphenylmethylthiourea scaffold, with potent intraocular pressure lowering properties

Reaction of thiophosgene with 4-aminomethyl-benzenesulfonamide afforded 4-isothiocyanatomethyl-benzenesulfonamide, which by reaction with amines, amino acids and oligopeptides, lead to a series of new sulfonamides incorporating a 4-sulfamoylphenyl-methylthiourea scaffold. These new thioureas showed strong affinities towards isozymes I, II and IV of carbonic anhydrase (CA, EC 4.2.1.1). In vitro inhibitory potency was good (in the low nanomolar range) for the derivatives of: amino-benzoic acids, β -phenyl-serine, α -phenyl-glycine, for those incorporating hydroxy- and mercapto-amino acids (Ser, Thr, Cys and Met), hydrophobic amino acids (Val, Leu, Ile), aromatic amino acids (Phe, His, Trp, Tyr; DOPA); dicarboxylic amino acids as well as di-/tri-/tetrapeptides among others. Such CA inhibitors displayed very good water solubility (in the range of 2-3%) as sodium (carboxylate) salts, with pH values for the solutions obtained of 6.5-7.0. Furthermore, in normotensive rabbits, some of them showed an effective and prolonged intraocular pressure (IOP) lowering when administered topically, as 2% solutions

Carbonic anhydrase inhibitors with strong topical antiglaucoma properties incorporating a 4-(2-aminopyrimidin-4-yl-amino)-benzenesulfonamide scaffold

Reaction of 4-(2-amino-pyrimidin-4-yl-amino)-benzenesulfonamide with alkyl/aryl-sulfonyl halides, acyl halides or arysulfonyl isocyanates afforded a series of derivatives which were tested for inhibition of three carbonic anhydrase (CA) isozymes. These compounds were designed in such a way as to (i) strongly inhibit several CA isozymes involved in aqueous humor secretion within the eye (such as CA II and CA IV), and (ii) to possess a pharmacological profile that allows easy penetration through the cornea, when administered as eye drops in solution or suspension, constituting thus a valuable therapeutic approach for glaucoma. Several of the obtained inhibitors showed low nanomolar affinities for the two isozymes involved in aqueous humor secretion, CA II and CA IV. Furthermore, in normotensive and hypertensive rabbits, some of them showed an effective and prolonged intraocular pressure (IOP) lowering when administered topically, as 2% suspensions/solutions

Formulazioni di cromofori di impiego nella saldatura laser di tessuti biologici

L'invenzione si riferisce a cromoforo formulazioni sotto forma di semisolido o solido da utilizzare per la colorazione di tessuti biologici al fine di assorbire in modo selettivo e localizzato la radiazione laser nei processi di saldatura laser di tessuti biologici. Queste procedure vengono applicate nei trattamenti chirurgici per la sutura, la guarigione e la sigillatura di incisioni e ferite in vari tipi di tessuti, come le membrane cornea, della pelle e le mucos

Carbonic anhydrase inhibitors: Topically acting antiglaucoma sulfonamides incorporating esters and amides of 3-and 4-carboxybenzolamide

Reaction of 3- and 4-carboxybenzenesulfonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulfonamide/5-imino-4-methyl-δ 2-1,3,4-thiadiazoline-2-sulfonamide afforded two series of benzolamide analogues to which the carboxyl moiety has been derivatized as esters or amides, in order to reduce their very polar character. The new derivatives showed low nanomolar affinity for three carbonic anhydrase (CA) isozymes, CA I, II and IV, and were effective as topical antiglaucoma agents in normotensive rabbits. Efficacy of several of the new sulfonamides reported was better than that of the standard drugs dorzolamide and brinzolamide, whereas their duration of action was prolonged as compared to that of the clinically used drugs

Healing of rabbits' cornea following laser welding: effect of solid and semisolid formulations containing indocyanine green

Laser-assisted tissue welding using chromophores and/or biomaterials as solders may offer several advantages over conventional methods (sutures and staples) such as reduced inflammation and foreign body response, faster healing, and simplicity. This technique makes it possible to perform sutureless surgery and repair wounds that are difficult or impossible to repair using standard surgical techniques. This in turn may be particularly important in ophthalmology, where conventional sutures may cause inflammation, tissue injury, scarring, and stenosis. The objective of this research was the preparation and technological and biological characterization of new solid (S) and semisolid (SS)formulations containing indocyanine green (ICG), which is a chromophore commonly used in laser welding or tissue soldering. The formulations were aimed at improving the cromophore-assisted laser welding process while ensuring the chemical stability of ICG. Polyvinyl alcohol (PVA), sodium hyaluronate (HYAL), sodium alginate (ALG), 5-methylpyrrolidinone chitosan (MPCh), and tamarind seed polysaccharide (TSP) were chosen as vehicles for the ocular application of ICG. The wetting and hydrophilicity characteristics of the solid formulations (film) were evaluated by contact angle and swelling measurements and correlated with the in vitro release of ICG. The biological efficacy of the formulations was evaluated on a corneal cut in a rabbit model by monitoring the healing process after laser welding and comparing it to the healing process of a conventional suture. The best results were obtained with a solid formulation based on TSP that showed high wettability, good chemical stability, and slow release of ICG. Its use resulted in a rapid and safe healing process

ESPRESSO: A novel device for laser-assisted surgery of the anterior eye segment

Introduction: Merging robotics with laser eye surgery could enhance precision, repeatability and automation. During some eye laser procedures the patient is awake, thus eye stabilization is desired to avoid movements that could affect the treatment. Material and methods: The ESPRESSO platform has a two-stage actuation system to position a stabilization tool on the eye, a proximity sensing unit to monitor the stabilization tool position, and a sensing unit to monitor the pressure exerted on the eye. The platform is tested in-vitro and ex-vivo with clinicians. A maximum pressure to be exerted on the eye is defined with expert ophthalmic surgeons to be 22 mmHg: physiological intraocular pressure (IOP) range is 10-21 mmHg. This pressure corresponds to a force of 0.3 N. Results: The necessary contact force to have eye fixation (according to the clinicians' feedback) is evaluated: maximum values resulted always below 0.3 N. A maximum IOP increase of 4.67 mmHg is observed, that is a slight variation with respect to the performance of other platforms (IOP elevations up to 328 mmHg). Conclusion: Design and initial assessment of the platform is presented. Eye stabilization is performed without exceeding the critical contact force value and causing large/sudden IOP increases