EP2265252A2 - Sterile ophthalmische zubereitungen und herstellungsverfahren dafür - Google Patents

Sterile ophthalmische zubereitungen und herstellungsverfahren dafür

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Publication number
EP2265252A2
EP2265252A2 EP09721331A EP09721331A EP2265252A2 EP 2265252 A2 EP2265252 A2 EP 2265252A2 EP 09721331 A EP09721331 A EP 09721331A EP 09721331 A EP09721331 A EP 09721331A EP 2265252 A2 EP2265252 A2 EP 2265252A2
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EP
European Patent Office
Prior art keywords
sodium
wax
oil
ophthalmic composition
group
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.)
Withdrawn
Application number
EP09721331A
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English (en)
French (fr)
Inventor
Ashok Vasantray Vyas
Ravindra Tukaram Jadhav
Subhash Trimbak Phad
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.)
Marvel Lifesciences Ltd
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Marvel Lifesciences Ltd
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Publication date
Application filed by Marvel Lifesciences Ltd filed Critical Marvel Lifesciences Ltd
Publication of EP2265252A2 publication Critical patent/EP2265252A2/de
Withdrawn legal-status Critical Current

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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
    • A61K31/435—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/38—Cellulose; 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

Definitions

  • the present invention relates to an ophthalmic composition.
  • the present invention relates to an ophthalmic composition used in the treatment of intraocular hemorrhage and macular degeneration.
  • Intraocular hemorrhage is a condition in which bleeding occurs in the eyeball . It may be the result of physical trauma (direct injury to the eye) and/or medical illness. Severe hemorrhage, particularly when leading to rising pressure inside the eye, may lead to blindness. There are different types of intraocular hemorrhage such as subconjunctival hemorrhage, hyphema, vitreous hemorrhage ,subretinal hemorrhage and submacular hemorrhage.
  • terson's syndrome as a result of subarachnoid hemorrhage
  • hemophilia a severe bleeding disorder, usually hereditary
  • anticoagulants and thrombolysis (medication to reduce blood clotting tendency or to disperse blood clots, respectively)
  • hemophthalmia is always accompanied by activation of free radical oxidation processes and proceeded as chain reactions and involves accumulation of oxidation products of molecules in vitreous body and retina.
  • Application of antioxidant preparations in early conservative therapy of intraocular hemorrhages essentially allows to speed up the resorption processes and thus reduce the risk of development of serious complications such as fibrosis of vitreous body and retinal detachment.
  • 3-Hydroxy-2,4,6-trimethylpyridine succinate and other such salts belong to new biologically active compounds which exhibit important pharmacological activities such as anti oxidant for the vascular and inflammatory eye pathology.
  • 3-Hydroxy- 2,4,6-trimethylpyridine succinate and other such salts also possess geroprotective action and can be used to treat conditions, diseases or disorders of the cornea, retina, lens, sclera , anterior and posterior segments of the eye.
  • macular degeneration degenerative disease of the eye
  • lipofuscin accumulation is implicated as a major risk factor.
  • Lipofuscin is finely granular yellow brown pigment, composed of lipid-containing residues of lysosomal digestion. It is considered one of the aging or "wear and tear" pigments. It appears to be the product of the oxidation of unsaturated fatty acids and may be symptomatic of membrane damage or damage to mitochondria and lysosomes.
  • 3-Hydroxy-2,4,6-trimethylpyridine has been found to be an active inhibitor of peroxide oxidation of lipids. Thus, it is capable of neutralizing toxic activity of lipofuscin granules to have geroprotective action.
  • PCT/IB2005/003636 discloses a method of preparing 2,4,6-trimethyl-3- hydroxypyridine derivatives and salts thereof having antioxidant, geroprotective and anti-ischemic activity.
  • an ophthalmic composition comprising 3-hydroxy- 2,4,6-trimethylpyridine, pharmaceutically acceptable salts, esters, derivatives and polymorphs thereof in an amount in the range of about 0.05 % to about 10 % of the mass of the composition, preservative in the range of about 0.005 % to about 0.5% of the mass of the composition, stabilizer in the range of about 0.01 % to about 1% of the mass of the composition, excipients in the range of about 0.02 % to about 5 % of the mass of the composition and a vehicle, wherein pH of said ophthalmic composition is in the range of about 4 to about 7.5.
  • the pharmaceutically acceptable salt of 3-hydroxy-2,4,6- trimethylpyridine is selected from a group of salts consisting of succinate, maleate, tartarate, oxalate, fumarate, citrate , hydrochloride, salicylate, pamoate, hydrogen sulfate, sulfate, methanesulphonate and benzenesulfonate.
  • the preservative is at least one selected from a group consisting of benzalkonium chloride, benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, chlorobutanol, metacresol, phenylmercuric nitrate, phenylmercuric acetate orphenylmercuric borate, thiomersal, myristylgamma picolonium chloride, phenol, benzoxonium chloride, cetrimide, phenyl ethanol, chlorohexidine and sodium perborate.
  • benzalkonium chloride benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, chlorobutanol, metacresol, phenylmercuric nitrate, phenylmercuric acetate orphenylmercuric borate, thiomersal, myristylgamma picolonium chloride, phenol, benzoxonium
  • the stabilizer is selected from a group consisting of thiourea, thiosorbitol, sodium dioctyl sulfosuccinate or monothioglycerol, sodium edetate, creatinine, glycine, niacinamide, sodium acetyltryptophanate, sodium caprylate, sodium saccharin, citric acid and salts thereof.
  • the excipients are selected from a group consisting of thickening agents, chelating agents, buffering agent, surfactants, tonicity agents, pH adjusting agents and solvents.
  • the thickening agent is at least one selected from a group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxy methyl cellulose, hydroxyethyl cellulose, polyethylene glycol, acrylates, methacrylates, gelatin, alginates, pectins, tragacanth, karaya gum, xanthan gum, carrageenin, agar, alginate, chitosan and acacia.
  • the chelating agent is selected from a group consisting of edetate disodium, edetate calcium disodium and edetate tetrasodium.
  • the buffering agent is at least one selected from a group consisting of acetic acid, adipic acid, benzoic acid, sodium benzoate, citric acid, lactic acid, maleic acid, potassium phosphate, sodium phosphate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium citrate, sodium tartarate, tartaric acid, sodium citrate dehydrate, sodium acetate trihydrate.
  • the surfactant is at least one selected from the group consisting of alkyl polyethylene oxide, alkylphenol polyethylene oxide, sodium laureth sulphate, sodium dodecyl sulphate, alkyl alcohol, sodium lauryl sulfate, polyoxyethylene/polyoxypropylene block polymers (poloxamers), glycerols, polyglycerols, fatty acids, polyethylene glycol hydroxystearate, polyalkyl glucosides, ceramides, polyethylene glycol/alkyl glycol copolymers, and polyethylene glycol/polyalkylene glycol ether di-block or tri-block copolymers, diacetylated monoglycerides, diethylene glycol monostearate, ethylene glycol monostearate, glyceryl monooleate, propylene glycol monostearate, macrogol esters, macrogol stearate, polyoxyethylene 50 stearate, macrogol ethers, cetomacro
  • the tonicity agent is at least one selected from a group consisting of glycerin, propylene glycol, polyethylene glycol, lactose, mannitol, dextrose, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium sulfate and sorbitol.
  • the pH adjusting agent is selected from a group consisting of sodium hydroxide, hydrochloric acid, triethanolamine, ammonia and mixtures thereof.
  • the vehicle is water for injection and said composition is in the form of a solution.
  • the vehicle is at least one ointment base selected from a group consisting of oil and wax and the ophthalmic composition is in the form of an ointment.
  • the oil is at least one selected from a group consisting of isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2- hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, ethylhexyl cocoate, dicaprylyl carbonate, cetearyl isononanoate, oleyl erucate, erucyl oleate, erucyl eru
  • the wax is at least one selected from a group of candelilla wax, carnauba wax, bees wax, espartograss wax, cork wax, guaruma wax, rice germ oil wax, sugarcane wax, berry wax, ouricury wax, montan wax, jojoba wax, shea butter, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial grease, ceresin, ozocerite (earth wax), paraffin waxes, sunflower wax, rlemon wax, grape fruit wax and laurel wax.
  • candelilla wax carnauba wax, bees wax, espartograss wax, cork wax, guaruma wax, rice germ oil wax, sugarcane wax, berry wax, ouricury wax, montan wax, jojoba wax, shea butter, beeswax, shellac wax, spermaceti, lanolin (wool wax),
  • the vehicle comprises at least one polymer selected from a group consisting hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxy methyl cellulose, hydroxyethyl cellulose, carbopol and the ophthalmic composition is in the form of a gel.
  • the ophthalmic composition prepared in accordance with the present invention comprises 3-hydroxy-2,4,6-trimethylpyridine, pharmaceutically acceptable salts, esters, derivatives and polymorphs thereof in an amount in the range of about 0.05 to about 10 % of the mass of the composition, preservative in the range of about 0.005 to about 0.5% of the mass of the composition, stabilizer in the range of about 0.01 to about 1% of the mass of the composition, excipients in the range of about 0.02 to about 5 % of the mass of the composition and a vehicle, wherein pH of said ophthalmic composition is in the range of 4 to about 7.5.
  • the ophthalmic composition prepared in accordance with the present invention comprises the pharmaceutically acceptable salt of 3-hydroxy-2,4,6- trimethylpyridine is selected from a group of salts consisting of succinate, maleate, tartrate, oxalate, fumarate, citrate , hydrochloride, salicylate pamoate, hydrogen sulfate, sulfate methanesulphonate and benzenesulfonate.
  • the preservative used in the ophthalmic composition is at least one selected from a group consisting of benzalkonium chloride, benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, chlorobutanol, metacresol, phenylmercuric nitrate, phenylmercuric acetate orphenylmercuric borate, thiomersal, myristylgamma picolonium chloride, phenol, benzoxonium chloride, cetrimide, phenyl ethanol, chlorohexidine and sodium perborate.
  • benzalkonium chloride benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, chlorobutanol, metacresol, phenylmercuric nitrate, phenylmercuric acetate orphenylmercuric borate, thiomersal, myristylgamma picolonium chloride,
  • the stabilizer is selected from a group consisting of thiourea, thiosorbitol, sodium dioctyl sulfosuccinate or monothioglycerol, sodium edetate, creatinine, glycine, niacinamide, sodium acetyltryptophanate, sodium caprylate, sodium saccharin, citric acid and salts thereof.
  • the pharmaceutically acceptable excipients which used in the ophthalmic composition prepared in accordance with the present invention are selected from a group consisting of thickening agents, chelating agents, buffering agent, surfactants, tonicity agents, pH adjusting agents and solvents.
  • the ophthalmic composition preferably includes at least one thickening agent selected from a group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxy methyl cellulose, hydroxyethyl cellulose, polyethylene glycol, acrylates, methacrylates, gelatin, alginates, pectins, tragacanth, karaya gum, xanthan gum, carrageenin, agar, alginate , chitosan and acacia.
  • at least one thickening agent selected from a group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxy methyl cellulose, hydroxyethyl cellulose, polyethylene glycol, acrylates, methacrylates, gelatin, alginates, pectins, tragacanth, karaya gum, xanthan gum, carrageenin, agar, alginate , chitosan and acacia.
  • the ophthalmic composition prepared in accordance with the present invention includes chelating agent which is selected from a group consisting of edetate disodium, edetate calcium disodium and edetate tetrasodium.
  • the buffering agent is selected from a group consisting of acetic acid, adipic acid, benzoic acid, sodium benzoate, citric acid, lactic acid, maleic acid, potassium phosphate, sodium phosphate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium citrate, sodium tartarate, tartaric acid, sodium citrate dehydrate, sodium acetate trihydrate.
  • the ophthalmic composition prepared in accordance with the present invention further includes at least one surfactant selected from the group consisting of alkyl polyethylene oxide, alkylphenol polyethylene oxide, sodium laureth sulphate, sodium dodecyl sulphate, alkyl alcohol, sodium lauryl sulfate, polyoxyethylene/polyoxypropylene block polymers (poloxamers), glycerols, polyglycerols, fatty acids, polyethylene glycol hydroxystearate, polyalkyl glucosides, ceramides, polyethylene glycol/alkyl glycol copolymers, and polyethylene glycol/polyalkylene glycol ether di-block or tri-block copolymers, diacetylated monoglycerides, diethylene glycol monostearate, ethylene glycol monostearate, glyceryl monooleate, propylene glycol monostearate, macrogol esters, macrogol stearate, polyoxyethylene 50 stearate
  • the tonicity of the ophthalmic composition prepared in accordance with the present invention is adjusted to tonicity of lachrymal fluid by addition of tonicity agent.
  • the tonicity agent used in the ophthalmic composition to adjust the osmotic pressure is at least one selected from a group consisting of glycerin, propylene glycol, polyethylene glycol, lactose, mannitol, dextrose, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium sulfate and sorbitol.
  • the pH of the ophthalmic composition is adjusted in the range of about 4 to about 7.5 to prevent eye irritation.
  • the pH adjusting agent is selected from a group consisting of sodium hydroxide, hydrochloric acid, triethanolamine, ammonia and mixtures thereof.
  • an ophthalmic composition is in the form of a solution and the vehicle used to prepare an ophthalmic solution is water for injection.
  • an ophthalmic composition is in the form of an ointment and the vehicle used to prepare an ophthalmic ointment is at least one ointment base selected from a group consisting of oil and wax.
  • the oil is at least one selected from a group consisting of isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, ethylhexyl cocoate, dicaprylyl carbonate, cetearyl isononanoate, oleyl erucate, erucyl oleate, erucyl erucate,
  • the wax is at least one selected from a group of candelilla wax, carnauba wax, bees wax, espartograss wax, cork wax, guaruma wax, rice germ oil wax, sugarcane wax, berry wax, ouricury wax, montan wax, jojoba wax, shea butter, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial grease, ceresin, ozocerite (earth wax), paraffin waxes, sunflower wax, rlemon wax, grape fruit wax and laurel wax.
  • candelilla wax carnauba wax, bees wax, espartograss wax, cork wax, guaruma wax, rice germ oil wax, sugarcane wax, berry wax, ouricury wax, montan wax, jojoba wax, shea butter, beeswax, shellac wax, spermaceti, lanolin (wool wax),
  • an ophthalmic composition is in the form a gel and the vehicle used to prepare an ophthalmic gel in accordance with the present invention is at least one polymer selected from a group consisting hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxy methyl cellulose, hydroxyethyl cellulose and carbopol.
  • Ophthalmic formulations in accordance with the present invention employing different salts of 3-hydroxy-2, 4, 6-trimethylpyridine were prepared in the form of solution, gel and ointment.
  • 3-hydroxy-2,4,6-trimethylpyridine succinate and other ingredients were dissolved in water for injection.
  • the pH of the solution was adjusted to 6.
  • the resultant solution was sterilized and aseptically filled into vials.
  • Glacial acetic acid - QS Glacial acetic acid - QS
  • a gel of 3-hydroxy-2,4,6-trimethylpyridine succinate was formulated as follows:
  • Carbopol 934P was dispersed in water for injection and stirred for 1 hour. Resultant dispersion was kept for soaking for 10 hours to form a clear gel. To this 3-hydroxy- 2, 4, 6-trimethylpyridine succinate dissolved in water for injection was added with continuous stirring. Further, benzalkonium chloride was added and stirred for 10 minutes. Finally, triethanolamine was added and pH of the gel was adjusted to 5.9. The formulation was sterilized and aseptically filled into the tubes.
  • the ointment base was prepared by melting together white soft paraffin, liquid paraffin, cetsteryl alcohol and hard paraffin. To this base, 3-hydroxy-2, 4, 6- trimethylpyridine succinate and benzalkonium chloride dissolved in water for injection were added and homogeneously blended. The pH of the ointment was adjusted to 5.8. The ointment was sterilized and aseptically filled into the tubes.
  • the efficiency of the ophthalmic composition comprising 3-hydroxy-2,4,6- trimethylpyridine prepared in accordance with the present invention, in traumatic hemophthalmia, on the basis of the modern ultrasonic researches of eyeglobe (eyeball) and parameters of biochemical researches of blood serum, tear liquid, liquid of the anterior chamber and eye tissue was studied.
  • a traumatic hemophthalmia was modeled by introduction of 0.5 to 0.7 ml of autoblood into a vitreous body through a puncture in a sclera on distance of 5 mm from a limbus, under a local anaesthesia.
  • the basic group made with 6 rabbits (12 eyes), daily received a formulation prepared in accordance with the present invention parabulbarly (0.5 ml of 1 % solution).
  • a high (100 - 50 SUD), medium (50 - 25 SUD) and low (less than 25 SUD) densities were distinguished.
  • the area measurement in sm 2 was used.
  • the volume of the intraocular hemorrhage was studied with the help of 3D modelling in the B-regimen of a grey scale and measurement in sm 3 .
  • the average volume of vitreous body (1.0 ⁇ 0.9 sm 3 ) and the average area of a vitreous body (1.04 ⁇ 0.8 sm 2 ) were fixed. Proceeding from the obtained data, the total hemophthalmia (from 100 up to 50 % of the vitreous body volume) was equated to the volume of 0.5-1.0 sm 3 and of 0.5-1.0 sm 2 , a wide-spread hemophthalmia (50 - 25 % of volume of a vitreous) corresponded to the area of 0.5-0.25 sm 3 . both 0.5-0.25 sm 2 , and the partial hemophthalmia occupied up to 0.25 sm 3 and 0.25 sm 2 (up to 25 % of the vitreous volume).
  • Capability of the eyeground ophthalmoscopy was estimated by a 3-mark(point) scale depending on the image sharpness (0 - ophthalmoscopy is impossible (not capable), 3 - details of an eyeground are clearly visible).
  • the materials used for biochemical examination were as follows: blood, liquid of the anterior chamber, tear liquid, tunics of eyeglobe (retina, a vitreous body).
  • the blood was taken from the aural vein in an amount of 3 ml.
  • Sampling of tear liquid was carried out by a microcapillary after instillation of distilled water into the conjunctival cavity.
  • Liquid of the anterior chamber was obtained by paracentesis.
  • the blood sampling as well as liquid of the anterior chamber and teat liquid were carried out on the 1 st , 7 th and 14 th day of the experiment.
  • the animals were killed (pithed) by air embolism and both the eyes were enucleated.
  • the eyes were prepared by tunic separation. Retina and vitreous body were obtained.
  • the concentration of products of the free radical oxidation, active in the reaction with thiobarbituric acid (TBA-active products), protein concentration, and the antioxidant activity (AOA) were determined.
  • Table No. 1 The data of preclinical and ultrasonic examinations at the experimental hemophthalmia in dynamics is shown in Table No. 1.
  • Table 1 Dynamics of parameters of preclinical and ultrasonic examination at the experimental hemophthalmia in the basic (A) and control (B) groups.
  • the parameters of ultrasonic and clinical examination were practically identical in all groups: the density of hemophthalmia in average made from 81 up to 85 SUD, the area - 0.52-0.55 sm 2 , the volume 0.47-0.5 sm 3 , the capability of ophthalmoscopy of an eyeground was corresponded to 1-2 points.
  • the intraocular hemorrhage which complicated the capability of ophthalmoscopy of an eyeground was marked rather small in volume, but essential in density.
  • the tendency to resorption of a hemorrhage was less expressed: the area of a hemophthalmia was 0.7 ⁇ 0.1 sm 2 , volume 0.68 ⁇ 0.9 sm 3 , density 65 ⁇ 2.1 SUD, capability of the eyeground ophthalmoscopy was 1 point. Thus, in animals of the control group the clinical picture practically did not changed.
  • the hemophthalmia was completely resolved in two animals, in other cases marked a noticeable decrease of the area (0.24 ⁇ 0,lsm 2 ), volume (0.2 ⁇ 0.1 sm 3 ) and density (23 ⁇ 1.1 SUD) of hemorrhage, the eyeground (2.2 points) was well seen.
  • the intraocular hemorrhage corresponded to a partial hemophthalmia with a low density.
  • the effect of treatment was less expressed: the area of a hemophthalmia averaged to 0.53 ⁇ 0.4 sm 2 , volume 0.5 ⁇ 0.2 sm 3 , density 48 ⁇ 1.5 SUD, capability of the eyeground ophthalmoscopy was equal to 1.8 points.
  • Table No.2 shows biochemical parameters in blood serum (BS), tear liquid (TL) and the anterior chamber liquid (ACL) at an experimental hemophthalmia in the basic (A) and the control (B) groups.
  • Table 2 Biochemical parameters
  • concentration of TBA-active products was grown in the control group (2.4 ⁇ 0.09 nmol/ml in the blood serum, 0.46 ⁇ 0.07 nmol/ml in the tear liquid, 2.2 ⁇ 0.4 nmol/ml in the anterior chamber liquid), and was reduced in the basic group (1.17 ⁇ 0.05 nmol/ml in the blood serum, 0.13 ⁇ 0.05 nmol/ml in the tear liquid, 0.8 ⁇ 0.5 nmol/ml in the anterior chamber liquid). Similar changes were observed at examination of protein concentration in the blood serum in rabbits of the control (103.0 ⁇ 5.0 mg / ml) and the basic (82.4 ⁇ 1.3 mg / ml) groups. In all animals the protein concentration was grown in the tear and the anterior chamber liquid on the 7 th day.
  • the ophthalmic composition prepared in accordance with the present invention renders a positive effect on the resorptive processes in a vitreous body at the experimental traumatic hemophthalmia.

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EP09721331A 2008-02-19 2009-02-19 Sterile ophthalmische zubereitungen und herstellungsverfahren dafür Withdrawn EP2265252A2 (de)

Applications Claiming Priority (2)

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IN355MU2008 2008-02-19
PCT/IN2009/000113 WO2009116076A2 (en) 2008-02-19 2009-02-19 Sterile opthalmic preparations and a process for preparation thereof

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EP2265252A2 true EP2265252A2 (de) 2010-12-29

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US20140018402A1 (en) * 2011-03-30 2014-01-16 Catholic University Industry Academic Cooperation Foundation Pharmaceutical composition for preventing or treating macular degeneration
CN102526282A (zh) * 2012-03-11 2012-07-04 周洁 一种降低糖尿病眼病的眼压的外用保健品
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CN109030474A (zh) * 2018-06-13 2018-12-18 迦娜生物科技（武汉）有限公司 一种脂质自由基尿液检测试剂及其应用
WO2020036242A1 (ko) * 2018-08-17 2020-02-20 주식회사 나이벡 치은치주염 또는 임플란트 주위염 치료 및 예방용 조성물 및 상기 조성물이 코팅되어 있는 치간칫솔
RU2703306C1 (ru) * 2018-09-27 2019-10-16 федеральное государственное автономное учреждение "Национальный медицинский исследовательский центр "Межотраслевой научно-технический комплекс "Микрохирургия глаза" имени академика С.Н. Федорова" Министерства здравоохранения Российской Федерации Способ повышения зрительных функций при эндовитреальной хирургии регматогенной отслойки сетчатки
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