WO2013046059A2 - Procédés et compositions destinés au traitement d'une maladie oculaire à base de tamarin en combinaison avec le tréhalose - Google Patents

Procédés et compositions destinés au traitement d'une maladie oculaire à base de tamarin en combinaison avec le tréhalose Download PDF

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WO2013046059A2
WO2013046059A2 PCT/IB2012/002608 IB2012002608W WO2013046059A2 WO 2013046059 A2 WO2013046059 A2 WO 2013046059A2 IB 2012002608 W IB2012002608 W IB 2012002608W WO 2013046059 A2 WO2013046059 A2 WO 2013046059A2
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concentration
eye
ophthalmic preparation
tamarind
trehalose
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PCT/IB2012/002608
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WO2013046059A3 (fr
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Robert C SYKORA
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Sykora Robert C
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Publication of WO2013046059A3 publication Critical patent/WO2013046059A3/fr

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    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016—Disaccharides, e.g. lactose, lactulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • 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

Definitions

  • the instant i nvention relates to an ophthalmic preparation for topical application to the eye, the preparation comprised of, among other ingredients, (a) tamarind and (b) trehalose-in amounts sufficient to treat an ocular disease characterized by dry eye, eye su rface inflammation, or eye surface damage.
  • Th is invention relates to a composition for treating an ocular disease characterized by dry eye, eye su rface inflammation, or eye surface damage and a related method of use.
  • the invention relates to a method of treating an ocular disease characterized by dry eye, eye surface inflammation, or eye su rface damage without an active pharmaceutical ingredient. More particularly, it relates to topical ophthalm ic preparations containing tamarind compounds and trehalose to suppress eye surface inflammation, heal eye su rface damage, or treat dry eye.
  • the ocu lar tear fluid is an organized l iquid which coats the conjunctiva and the exposed surface of the eyebal l.
  • the tear fil m appears to be a complex three-layered structure that is comprised of: (a) a layer of mucus, consisting of a mixture of glycoproteins (mucin) produced by specialized cells (i.e.
  • the conju nctival goblet cel ls which are present in the conju nctival epitheliu m— said layer is adsorbed on the cornea, thus forming a hydrophilic su rface;
  • a thick intermediate aqueous layer spread over said hydrophil ic su rface, consisti ng essentially of water, electrolytes, proteins, enzymes and mucin;
  • a thi n external l ipid layer having the main function of control ling the water evaporation rate from the tear film. 0004.
  • the eyelid movement squeezes the mucus out of the conjunctival cells and introduces it into the fornices.
  • the three-layered structure descri bed above constitutes a complex physiological system , mainly directed to protect the eye su rface, to maintai n the hydration, the lu brication and the clearness of the corneal surface, and to cooperate in producing a correct vision.
  • the perfect equil ibrium and continuous renovation of said physiological system is a necessary condition for it to be able to carry out said functions.
  • a steady rate of water evaporation from the tear flu id must take place, so as to keep the osmolarity matched to the physiological level of about 300 mOsm /liter.
  • the tear film must be conti nuously redistributed on the corneal su rface as a result of blinki ng.
  • the i ntegrity of the internal mucin layer represents one of the essential elements of the maintenance of the tear film stability.
  • Mucin enhances the wettability of the corneal su rface, allows the aqueous film to keep adhering to the exposed surface in a continuous and homogeneous way, thus safeguarding its stability, and i ncreases the viscosity of the lacrimal flu id, preventing it from flowing away too rapidly from the conjunctival sac.
  • mucin is absent or insufficient, the cornea becomes non-wettable and, as a consequence of the unbalance between electrolytes and glycoproteins present, the tear fi lm becomes unstable and subject to breaki ng, with subsequent formation of d ry areas.
  • Eye su rface dryness includes any ocular disorder resu lting in loss of water from the tear film. Such disorders generally can be characte rized by i ncreased tear film osmolarity and decreased levels of corneal glycogen and conjunctival mucu s-containing goblet cells. Eye surface dryness can resu lt from a nu mber of different diseases including, for example, meibomian gland dysfunction and meibomian gland orifice stenosis or closu re.
  • Eye su rface inflammation includes any inflam matory d isorder involvi ng the ocular surface.
  • the eye su rface includes the eye lids, conjunctiva and cornea.
  • Inflammation refers to white blood cell or leu kocytic infiltration associated with cellular injury.
  • Eye su rface inflammatory disorders treatable by the ophthalmic preparation of the invention are typical ly manifested by signs and symptoms such as eye redness, or irritation. These diseases include, for example, meibom ianitis, blepharitis conjunctival hyperemia, eyelid hyperemia, keratitis and ocular rosacea. Eye surface inflammatory disorders are often associated with eye su rface dryness and irritation. "Eye Surface Damage” includes any injury involvi ng the ocular su rface.
  • the ocular surface can be damaged by many cond itions including chemical /thermal injuries, conjunctival scarring conditions such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid, chronic infections or inflammation of normal tissue growth on the conju nctiva such as pterygium or tu mors, damage to the sensory nerves of the cornea such as dysautonimia or Riley-Day syndrome, or rare hereditary conditions.
  • conjunctival scarring conditions such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid
  • chronic infections or inflammation of normal tissue growth on the conju nctiva such as pterygium or tu mors
  • damage to the sensory nerves of the cornea such as dysautonimia or Riley-Day syndrome
  • rare hereditary conditions usually result in extensive damage to the ocular surface and lead to abnormal proliferation of the conjunctival cells on the corneal surface and abnormal blood vessel formation with scarring. Severe damage of
  • Dry eye as a multifactorial disease of the tears and ocu lar su rface that results in symptoms of discomfort, visual disturbance, 5-7 and tear fi lm i nstability with potential damage to the ocu lar su rface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular su rface.
  • mucus is characterized by crystallizing i n a fern pattern when made to evaporate at room temperatu re from an aqueous solution.
  • the ferning phenomenon which is believed to result from the interaction of the electrolytes with the high molecu lar weight g lycoprotei ns of mucus, is evidenced after a short time from the collection of tear mucus from the lower fornix of the conjunctiva.
  • a dense ferni ng for instance, is considered to be the expression of a perfect equ ilibrium between muci n and electrolytes, while the partial presence or the absence of tear ferning, which is detected in eyes affected by keratoconju nctivitis sicca, denotes a quantitative lack of tear mucus or a qualitative alteration of the glycoproteins or of their envi ronment (i.e., pH, hydration, electrolytic equilibriu m).
  • dry eye syndrome may be detected and monitored not only by means of the evaluation of the typical symptoms thereof, but also by means of well established procedures, i ncluding, as the most common, the evaluation of lacrimal secretion (Schirmer test), the evaluation of the ti me needed for the tear film to break after a compete bl ink (break-up time. BUT), and the evaluation of the color of the corneal and/or conjunctival surface u pon staining with rose Bengal, fluorescein, or lissamine green.
  • Keratoconju nctivitis sicca is normally treated with liquid ophthalmic preparations generally known as "artificial tears", to be instilled in d rops in order to replace or su pplement the natural tear production.
  • said preparations have only a moistening effect, as they consist of physiological saline solutions, neutral and isotonic with the lacrimal flu id, based on sodiu m chloride only or on balanced mixtu res of various electrolytes.
  • An example of such a preparation comprising at least four different ionic species (i.e.
  • potassiu m, sodiu m, chloride and bicarbonate in concentrations su itable to reproduce as faithfully as possible the electrolyte composition of the tear fluid, is disclosed i n EP-A-0 205 279.
  • Such preparations as do the simpler physiological solutions, reach the objects of increasing the tear volu me, moisteni ng the ocu lar su rface, diluting the mucus deposits and washing away any debris and foreign bodies.
  • said preparations have an extremely short duration of action (of the order of a few m inutes), since the solution readily drains into the conjunctival sac.
  • 4,409,205 discloses a composition for ophthalmic use, which can serve both as an artificial tear substance and as a carrier for therapeutical ly active agents, wherein the viscosity enhancing agent is a non-ionic synthetic polymer, selected between polyvinyl alcohol , polyethylene glycol and mixtures thereof.
  • the viscosity enhancers to confer advantageous featu res to a composition for use as artificial tear, is not sufficient that these viscosity enhancers generically increase the viscosity of the product, but it is also necessary that the dispersions thus formed have properties as close as possible to those of mucin dispersions. Namely, these dispersions must behave as much as possible as mucom imetic substances.
  • compositions for use as artificial tears having non-newtonian rheologic behaviou r are disclosed in WO-A-8404681 and in U.S. Pat. No. 5 , 1 06,61 5.
  • the first document proposes the use of carboxyvinyl polymers such as Carbopol.RTM. , to be i ncluded in the formulation in amounts from 0.05 to 0.25% by weight, as viscosity enhancing agents for ophthalm ic solutions.
  • the resulting solutions show, according to this document, a non-newtonian behavior wh ich is currently defined as "plastic", characterized by a yield value for the shear stress, below which value no flow occurs.
  • plastic characterized by a yield value for the shear stress, below which value no flow occurs.
  • compositions useful both as artificial tears and as carriers for ophthalmic medicaments which are viscosified with anionic polymers of high molecular weight (comprised between 500,000 and 4,000,000).
  • anionic polymers of high molecular weight (comprised between 500,000 and 4,000,000).
  • carboxyvinyl polymers mentioned above and hyaluronic acid are mentioned as preferred.
  • Hyaluronic acid is a polysaccharide of natu ral origin present i n many tissues and fluids, both human and animal, and largely employed in ophthalmic preparations, owing to the marked pseudoplastic behaviour of its aqueous solutions.
  • Equally diffused as thickening agents and viscosity enhancers capable of imparting to the resu lting composition the desired non-newtonian rheology are the cellulose esters, such as methylcellu lose and the alcoholic derivatives thereof, e.g. hydroxypropylcellu lose and hydroxypropyl methylcellulose. 001 1 .
  • a product for use as an ophthalmic solution in order to suitably replace and mimic the mucin component of the tear fluid, a product for use as an ophthalmic solution must not only show a pseudoplastic rheological behavior, but also it must show other properties similar to those of muci n.
  • erodible ocular inserts to be placed in the conju nctival sac.
  • Said inserts consist, e.g. , of smal l cyl inders made of hydroxypropylcellulose which, d issolving in the conjunctival sac, continuously provide the viscosifying and lu bricating mucomimetic su bstance.
  • Such inserts have the advantage of being totally free of preservatives, they can be d ifficult to insert, and their presence in the conjunctival sac adds to the foreign body sensation, which is always present in cases of dry eye syndrome.
  • the erodible conju nctival inserts cause temporary vision disturbance, owing to the excess of polymer on the corneal su rface.
  • Phospholipid compositions have been shown to be usefu l in treating dry eye; see, e.g., McCulley and Shine, Tear film structure and Dry eye, Contactologia , volume 20(4), pages 1 45-49 (1 998); and Shine and McCu lley, Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality, Archives of Ophthalmology , volu me 1 1 6(7), pages 849-52 (1 998).
  • Examples of phospholipid compositions for the treatment of Dry eye are disclosed in U.S. Pat. No. 4, 1 31 ,651 (Shah et al.), U.S. Pat. No. 4,370,325 (Packman), U.S. Pat.
  • Corticosteroids such as prednisolone and loteprednol, reduce inflammation but cannot be used for prolonged therapy i n dry eye patients due to the propensity of steroids to elicit ocular side effects.
  • Steroid-related complications i ncluding increased intraocular pressure and cataract formation have been observed in dry eye patients treated with corticosteroids after several months of therapy. See Marsh, et al., Ophthalmologv, 1 06(4): 81 1 -81 6 ( 1 999). Marsh, et al.
  • Agents clai med for increasi ng ocular mucin and/or tear production include vasoactive intesti nal polypeptide (Dartt et. al., Vasoactive intestinal peptide - stimulated glycocongjugate secretion from conjunctival goblet cells. Experimental Eve Research , volume 63 , pages 27-34, ( 1 996)), gefarnate (Nakmu ra et.
  • U.S. Pat. No. 5,696,1 66 discloses the use of certain HETE derivatives, including 1 5- H ETE, for treating dry eye and other disorders requiring the wetting of the eye.
  • the HETE derivatives stimu late mucin production and /or secretion in the conjunctival epithelium and goblet cells.
  • the HETE derivatives are topically ad ministered to the eye.
  • 1 5-HETE has been shown to increase the secretion of mucin-1 (MUC- 1 ) from hu man conjunctival epithelial cells.
  • the present invention is a therapeutic preparation for ophthalmic use that provides the advantage of drug delivery and treatment or prevention of dry eye disease, eye su rface inflammation, or healing of eye surface damage.
  • the composition comprises an aqueous preparation of the mucomimetic ingredients tamari nd seed polysaccharide (TSP) and trehalose disaccharide, the demulcents polyvi nyl alcohol and polyethylene glycol 400, a preservative such as polyhexamethylene biguanide (PHMB) , in an electrolye-based solution that may include a combination of the followi ng: sod ium chloride, potassium chloride, magnesiu m hydroxyhexahydrate, sodium phosphate monbasic monohyd rate, and calcium ch loride dehydrate, which may be applied topically to the eye, permitting the maintenance or restoration of essentially normal levels of conju nctival mucus and corneal glycogen.
  • TSP tamari nd seed polysaccharide
  • FIGURE 1 - TREHALOSE DISACCHARIDE CHEM ICAL STRUCTURE
  • FIGURE 2 TAMARIND POLYSACCHARIDE CHEM ICAL STRUCTURE
  • the present invention is directed to a dry eye composition
  • a dry eye composition comprising an aqueous solution of fou r polyols: two polysaccharides and two demu lcents.
  • the composition has been shown to moisturize the eye for a relatively long duration.
  • the efficacy of the dry eye medication described herein depends upon the novel combination of two polysaccharides: tamarind seed extract and trehalose disaccharide.
  • the mucoadhesive polymer extracted from tamari nd seeds has been described as a viscosity enhancer showing mucomimetic, mucoadhesive, and bioadhesive activities [ref] .
  • TSP tetrachlorosulfate sulfate
  • trehalose disaccharide present in a concentration range of approximately 3.5% to 4%, is implicated in anhydrobiosis — the ability of plants and animals to withstand prolonged periods of desiccation. It has high water retention capabilities, and is used in food and cosmetics.
  • the sugar is thought to form a gel phase as cells dehydrate, which prevents disruption of internal cell organelles, by effectively splinti ng them in position. Rehydration then allows normal cellular activity to be resumed without the major, lethal damage that wou ld normally follow a dehydration / rehydration cycle.
  • Trehalose has the added advantage of being an antioxidant, further protecting the ocular and periocular tissues.
  • the polyols of the present invention are selected from the grou p consisting of glycerin, ethylene glycol, poly (ethylene glycol), propylene glycol, polyvi nyl alcohol, sorbitol , manitol and monosaccharides, disaccharides and oligosaccharides.
  • the present com position may also contain a disinfecting amount or a preservative of an anti microbial agent.
  • Antimicrobial agents are defi ned as organic chemicals that derive their anti microbial activity through a chemical or physiochemical interaction with the microbial organisms. These include sorbic acid , quarternary ammonium polymers and low and high molecular weight biguanides.
  • biguanides include the free bases or salts of alexidine, chlorhexidine, hexamethylene biguanides and their polymers, and combi nations of the foregoi ng.
  • the salts of alexid ine and chlorhexidine can be either organic or inorganic and are typically gluconates, nitrates, acetates, phosphates, sulfates, halides and the like.
  • a preferred polymeric biguanide is poly(hexamethylene biguanide) commercially available from Zeneca, Wilmington, Del. under the trademark CosmocilTM CQ.
  • the hexamethylene biguanide polymers also referred to as poly(aminopropyl biguanide) (PAPB), have molecular weights of up to about 1 00 kDa.
  • PAPB poly(aminopropyl biguanide)
  • a particularily preferred preservative is alexid ine.
  • the antimicrobial agent should be used in an amou nt which will preserve or prevent the growth of the microorganism popu lation in the formulations employed.
  • such agents are present in a minimum concentration of about 0.0001 wt. %, 0.0003 wt. % or 0.0005 wt. % and a maxi mum concentration of about 0.0005 wt. % or 0.001 wt. % or about 0.005 wt. % or about 0.01 wt. % or 0.02 wt. % based upon the total weight of the composition.
  • the aqueous solutions employed in this invention may contain additional ingredients described above, one or more other components that are commonly present in ophthalmic solutions, for example, sodium chloride, potassium chloride, magnesiu m chloride hexahydrate, sodiu m phosphate monobasic monohydrate, and calcium chloride d ihydrate.
  • the aqueous solutions of the present invention are typically adjusted with tonicity agents to create a hypotonic preparation to yield an osmolarity range of 1 50- 1 80 Osm that stabilizes the hypertonic tears of dry eye to approximate the tonicity of normal lacrimal fluids which is equivalent to a 0.9 wt. % solution of sodium chloride or approximately 31 6 Osm.
  • Suitable buffers may be added, such as borate, citrate, bicarbonate, aminoalcohol buffers, MOPS buffer, bicine, tricine, TRIS, BIS/TRIS and various mixed phosphate buffers (including combinations of Na 2 H PO 4 , NaH 2 PO 4 and KH 2 P0 4 ) and mixtu res thereof. Borate buffers are preferred, particularly for enhancing the efficacy of PAPB.
  • Preferred combination buffers include borate/ phosphate and borate/citrate combi nation buffers.
  • buffers will be used in amounts having a minimum of about 0.05 wt. % or about 0.1 wt. % and/or a maximum of about 1 .5 wt. % or about 2.5 wt. %.
  • the dry eye treatment can be formu lated as instant release and modified release dosage forms, including delayed-, extended-, prolonged-, sustai ned-, pulsatile-, control led-, accelerated-, fast-, targeted-, and program med-release dosage forms.
  • These dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art (see, Rathbone et ai, eds., 2008, Remington: The Science and Practice of Pharmacy, supra; Modified-Release Drug Delivery Technology, 2 nd ed., New York, NY: Marcel Dekker, I nc.).
  • the treatments can be administered by a health care practitioner or by the subject. I n some embodiments, the subject adm inisters the dry eye medication to hi m or herself.
  • the eye-drop treatment containing tamarind and trehalose will be thermo-reversible viscosity effects.
  • thermaloreversible is meant an increase in viscosity with an increase in tem peratu re.
  • a dry-eye formu lation that is administered as a low viscosity l iqu id at room tem perature and which "gels" on the ocu lar su rface will increase the residence ti me of the ingredients, thus prolonging the effect.
  • the eye-drop treatment will be applied cold, to provide a soothing "feel ing" to the eye.
  • the eye-drop treatment will be applied via a precise dose eye-drop applicator to prevent "run-off".
  • the medicament will be applied i n the form of a mist-delivering applicator.
  • the dry eye medicament can also comprise liposomes, micelles, m icrospheres, microparticles, nanosystems, e.g., nanoparticles, nano-coacervates and mixtu res thereof.
  • the nano-sized delivery matrix is fabricated through a well-defined process, such as a process to produce tamarind and /or trehalose encapsulated in a polymer. I n another em bodiment, the tamarind and trehalose combination spontaneously assembled in aqueous solutions, such as in liposomes and micelles.
  • the formulation for topical administration will be lipid-based.
  • a formulation in ointment form comprises one or more of the following ingredients: wool alcohol (acetylated lanolin alcohol), hard paraffin, white soft paraffin, liquid paraffin, and water. See, e.g., Langtry et a/., supra.
  • the selected formulation is inconspicuous when applied to the ocu lar surface, for example, is colorless, odorless, quickly-absorbing, etc.
  • the selected formu lation is applied on the ocu lar surface as a solution, wh ich can crosslink into a hydrogel within a few minutes, thus creating a biocompatible dressing.
  • the hydrogel may be biodegradable.
  • the solution wi ll absorb into the ski n and crossl ink i nto depots releasing drug.
  • Pharmaceutically acceptable carriers and excipients suitable for use in ocular formulations include, but are not limited to, aqueous vehicles, water-miscible vehicles, non-aqueous vehicles, anti-microbial agents or preservatives against the growth of microorganisms, stabilizers, solubility enhancers, isoton ic agents, buffering agents, antioxidants, local anesthetics, suspending and dispersing agents, wetting or e mulsifying agents, com plexi ng agents, sequestering or chelating agents, penetration enhancers, cryoprotectants, lyoprotectants, thickening agents, and inert gases.
  • Forms for ocular admi nistration can also be in the form of oi ntments, creams, emulsions, sprays, eye baths, and gels.
  • Su itable ointment vehicles include oleaginous or hydrocarbon vehicles, olive oil, cottonseed oil, mineral oil and other oils, white petrolatum , paraffins; emu lsifiable or absorption vehicles, such as hydrophilic petrolatum , hydroxysteari n sulfate, and anhydrous lanolin; water- re movable vehicles, such as hydrophil ic ointment; water-soluble ointment vehicles, including polyethylene glycols of varying molecular weight; emu lsion vehicles, either water-i n-oi l (W/O) emulsions or oil— in— water (O/W) emu lsions, includ ing cetyl alcohol , glyceryl monostearate,
  • Suitable cream base can be oil-in-water or water-in-oil .
  • Suitable cream vehicles may be water-washable, and contai n an oil phase, an emulsifier, and an aqueous phase.
  • the oil phase is also called the "internal" phase, which is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol .
  • the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a hu mectant.
  • the emulsifier in a cream formu lation may be a nonionic, anionic, cationic, or amphoteric su rfactant.
  • Gels are semisolid, suspension-type systems. Single- phase gels contain organic macromolecules distributed substantially uniformly throughout the liquid carrier.
  • Suitable gelling agents include, but are not limited to, crosslinked acrylic acid polymers, such as carbomers, carboxypolyalkylenes, and CARBOPOL ® ; hydrophilic polymers, such as polyethylene oxides, polyoxyethylene-polyoxypropylene copolymers, and polyvinylalcohol; cellulosic polymers, such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and methylcellu lose; gums, such as tragacanth and xanthan gum; sodiu m alginate; and gelatin.
  • dispersing agents such as alcohol or g lycerin can be added, or the gelling agent can be d ispersed by tritu ration, mechanical mixing, and/or stirring.
  • compositions intended for ocular administration can include one or more pharmaceutically acceptable carriers and excipients, includi ng, but not limited to, aqueous vehicles, water-misci ble vehicles, non-aqueous vehicles, anti-microbial agents or preservatives agai nst the growth of microorganisms, stabil izers, solubi lity enhancers, isotonic agents, buffering agents, antioxidants, local anesthetics, suspending and dispersing agents, wetting or emulsifying agents, complexing agents, sequestering or chelating agents, cryoprotectants, lyoprotectants, thickening agents, pH adjusting agents, and inert gases.
  • pharmaceutically acceptable carriers and excipients include one or more pharmaceutically acceptable carriers and excipients, includi ng, but not limited to, aqueous vehicles, water-misci ble vehicles, non-aqueous vehicles, anti-microbial agents or preservatives agai nst the growth
  • compositions for ocular adm inistration can be formu lated as a suspension, sol id, semisolid, or thixotropic liquid, for administration as an implanted depot.

Abstract

L'invention concerne une préparation ophtalmique pour application topique sur l'œil, la préparation étant constituée, entre autres ingrédients, (a) de tamarin et (b) de tréhalose en des quantités suffisantes pour traiter une maladie oculaire caractérisée par une sécheresse oculaire, une inflammation superficielle de l'œil, ou une lésion superficielle de l'œil.
PCT/IB2012/002608 2011-09-27 2012-09-25 Procédés et compositions destinés au traitement d'une maladie oculaire à base de tamarin en combinaison avec le tréhalose WO2013046059A2 (fr)

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Cited By (4)

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US9555054B2 (en) 2012-11-21 2017-01-31 University Of Louisville Research Foundation, Inc. Compositions and methods for reducing oxidative damage
CN111821333A (zh) * 2015-07-13 2020-10-27 东北泰克诺亚奇股份有限公司 视神经保护用组合物
CN114177280A (zh) * 2021-12-17 2022-03-15 上海卫康光学眼镜有限公司 一种含稳定性抗氧化酶的洗眼液及其制备方法
US11406591B2 (en) 2015-02-09 2022-08-09 University Of Louisville Research Foundation, Inc. Ophthalmic compositions and methods for reducing oxidative damage to an eye lens

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