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WO2002002122A1 - Ophthalmological drops with anti-imflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid - Google Patents

Ophthalmological drops with anti-imflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid Download PDF

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Publication number
WO2002002122A1
WO2002002122A1 PCT/SK2001/000018 SK0100018W WO0202122A1 WO 2002002122 A1 WO2002002122 A1 WO 2002002122A1 SK 0100018 W SK0100018 W SK 0100018W WO 0202122 A1 WO0202122 A1 WO 0202122A1
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WO
WIPO (PCT)
Prior art keywords
weight
distilled water
azidamphenicol
sodium
dexamethasone
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Ceased
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PCT/SK2001/000018
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French (fr)
Inventor
Vladimir Jancus
Jozef Ambro
Elena SLUCIAKOVÁ
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Unimed Pharma sro
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Unimed Pharma sro
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Priority to PL01354056A priority Critical patent/PL354056A1/en
Priority to UA2002031750A priority patent/UA53917A/en
Priority to AU2001266548A priority patent/AU2001266548A1/en
Priority to ROA200200235A priority patent/RO121087B1/en
Publication of WO2002002122A1 publication Critical patent/WO2002002122A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions

Definitions

  • Present technical solution relates to ophthalmological drops with anti- inflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid.
  • a number of ophthalmological preparations, known so far, based on a wide- spectrum antibiotic and a local glucocorticoid is now complemented with drops according to the present technical solution, the nature of which consists in that they contain from 0.1 to 2 % by weight of the wide-spectrum antibiotic azidamphenicol and from 0.01 to 1 % by weight of glucocorticoid dexamethasone or possibly its phosphate or acetate salt as the active substance, further from 0.0005 to 0.1 % by weight of a preserving additive, from 0.001 to 2 % by weight of substances which keep the pH value of the medium within a range from 4.5 to 7.5, from 0.01 to 5 % by weight of substances which ensure viscosity of the medium to be within a range of 5 to 25 mPa.s, and the rest to 100 % by weight consists of distilled water.
  • the substances which keep the pH value of the medium within a range from 4.5 to 7.5 include sodium acetate, sodium chloride, boric acid, borax, disodium edetate, sodium hydrogen phosphate or sodium dihydrogeri phosphate, alone or in a mixture.
  • the substances which ensure viscosity of the medium to be within a range of 5 to 25 mPa.s include hydroxypropylmethylcellulose, polyvinyl alcohol, polyoxyethylenesorbitan monooleate, alone or in a mixture.
  • the preserving additive is benzalkonium chloride, carbetopendecinium bromide, thimerosal, chlorohexidine or chlorobutanol.
  • azidamphenicol is a synthetic analogue of the wide- spectrum antibiotic chloramphenicol with identical antimicrobial spectrum. It is liposoluble, it diffuses through a bacterial membrane and it binds to ribosomes, it hinders bacterial proteosynthesis by inhibiting the peptide synthetase. At higher doses it acts bacteriostatically on a wide spectrum of microorganisms and even bactericidally on certain sensitive microorganisms. Probability of resistance is minimal. When applied topically to an eye it shows low toxicity and is well " tolerated by the eye tissue.
  • the second active substance is dexamethasone, a synthetic monofluorinated glucocorticoid without a mineralocorticoidal effect which is present in the form of a sodium salt.
  • Dexamethasone shows very strong and pronounced anti-inflammatory effect, combined with an antiallergic, analgesic and antiproliferative effect.
  • Indications for the combined preparation according to the present solution include inflammatory processes of the eye structures where anti-inflammatory effect is required together with simultaneous suppression of arising or of a risk of arising of secondary bacterial infection.
  • An advantage of the eye drops according to the present solution is a simultaneous good efficiency and stability at temperatures of up to 25 °C.
  • the amounts of components of a production batch are a linear function of the amounts per one package, i. e. 10 ml.
  • composition for one package azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g borax - 0.00100 g disodium edetate 0.00010 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g
  • composition for one package azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g polysorbate 0.00100 g disodium edetate 0.00010 g polyvinyl alcohol 0.00100 g benzalkonium chloride 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium acetate 0.01000 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g chlorohexidine 0.00005 g sterilized distilled water ad 10 ml d) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g boric acid 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium hydrogen phosphate 0.01000 g sodium dihydrogen phosphate 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g chlorobutanol 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium chloride 0.00100 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g carbetopendecinium bromide 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g borax 0.00100 g disodium edetate 0.00010 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml h) Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g polysorbate 0.00100 g disodium edetate 0.00010 g polyvinyl alcohol 0.00100 g benzalkonium chloride 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium acetate 0.01000 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g chlorohexidine 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone 0.00100 g boric acid 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium hydrogen phosphate 0.01000 g sodium dihydrogen phosphate 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g chlorobutanol 0.00005 g sterilized distilled water ad 10 ml 1)
  • Composition for one package azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium chloride 0.00100 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g carbetopendecinium bromide 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g borax 0.00100 g disodium edetate 0.00010 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g polysorbate 0.00100 g disodium edetate 0.00010 g polyvinyl alcohol 0.00100 g benzalkonium chloride 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium acetate 0.01000 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g chlorohexidine 0.00005 g sterilized distilled water ad 10 ml
  • Composition for one package azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g boric acid 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium hydrogen phosphate 0.01000 g sodium dihydrogen phosphate 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose . 0.00100 g chlorobutanol 0.00005 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium chloride 0.00100 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g carbetopendecinium bromide 0.00005 g sterilized distilled water ad 10 ml
  • the amounts of components of a production batch are a linear function of the amounts per one package, i. e. 10 ml.
  • composition for one package azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g polysorbate 0.50000 g disodium edetate 0.02000 g polyvinyl alcohol 0.50000 g benzalkonium chloride 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium acetate 0.20000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g chlorohexidine 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g boric acid 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml e) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium hydrogen phosphate 0.20000 g sodium dihydrogen phosphate 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g chlorobutanol 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium chloride 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g carbetopendecinium bromide 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g borax 0.20000 g disodium edetate 0.02000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g polysorbate 0.50000 g sodium edetate 0.02000 g polyvinyl alcohol 0.50000 g benzalkonium chloride 0.01000 g sterilized distilled water ad 10 ml
  • Composition for one package azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium acetate 0.20000 g polysorbate 0.20000 g hydroxypropylmethyl cellulose 0.20000 g chlorohexidine 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone 0.20000 g boric acid 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone 0.20000 g - sodium hydrogen phosphate 0.20000 g sodium dihydrogen phosphate 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g chlorobutanol 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium chloride 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g carbetopendecinium bromide 0.01000 g sterilized distilled water ad 10 ml m)
  • Composition for one package azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g borax 0.20000 g disodium edetate 0.02000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g polysorbate 0.50000 g disodium edetate 0.02000 g polyvinyl alcohol 0.20000 g benzalkonium chloride 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium acetate 0.20000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g chlorohexidine 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g boric acid 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml q) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium hydrogen phosphate 0.20000 g sodium dihydrogen phosphate 0.20000 g disodium edetate 0.02000 g hydroxypiOpylmethylcellulose 0.20000 g chlorobutanol 0.01000 g sterilized distilled water ad 10 ml
  • composition for one package azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium chloride 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g carbetopendecinium bromide 0.01000 g sterilized distilled water ad 10 ml
  • the eye drops according to the present technical solution can be utilized in ophthalmology in the case of inflammatory processes of the eye structures, where combined anti-inflammatory and antibacterial treatment is useful, in particular eye inflammations which are sensitive to glucocorticoids and which are accompanied with bacterial infection or where a risk of bacterial infection of the eye exists.
  • eye inflammations which are sensitive to glucocorticoids and which are accompanied with bacterial infection or where a risk of bacterial infection of the eye exists.
  • eye inflammations which are sensitive to glucocorticoids and which are accompanied with bacterial infection or where a risk of bacterial infection of the eye exists.
  • These are, for example, blepharoco ⁇ junctivitis, superficial keratitis (nonpurulent, nonviral), inflammatory processes of sclera, chronical and acute allergic conjunctivitis.

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Abstract

Ophthalmological drops with anti-inflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid contained from 0.1 to 2 % by weight of azidamphenicol, from 0.01 to 1 % by weight of dexamethasone or its phosphate or acetate salts as the active substance, further from 0.0005 to 0.1 % by weight of a preserving additive, from 0.001 to 2 % by weight of substances which keep the pH value of the medium within a range from 4.5 to 7.5, from 0.01 to 5 % by weight of substances which ensure viscosity of the medium to be within a range of 5 to 25 mPas.s, and the rest to 100 % by weight consists of distilled water.

Description

Ophthalmological drops with anti-inflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid
Technical Field
Present technical solution relates to ophthalmological drops with anti- inflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid.
Background Art
In ophthalmology, a number of combined preparations based on a wide- spectrum antibiotic and a local glucocorticoid have been used up to now, such as Spersadex comp. (active substances: dexamethasoni natrii phosphas, chloramphenicolum), Maxitrol (active substances: dexamethasonum, neomycini sulfas, polymyxini-B sulfas), Sofradex (active substances: dexamethasoni natrii sulfobenzoas, framycetini sulfas, gramicidinum), Tobradex (active substances: dexamethasonum, tobramycinum), Spersadex comp. being the preparation, composition of which is closest to the presently solved state. The problem for its common usage is its limited stability - it is necessary to store, it at a temperature of 2 to 8 °C.
Description of Technical Solution
A number of ophthalmological preparations, known so far, based on a wide- spectrum antibiotic and a local glucocorticoid is now complemented with drops according to the present technical solution, the nature of which consists in that they contain from 0.1 to 2 % by weight of the wide-spectrum antibiotic azidamphenicol and from 0.01 to 1 % by weight of glucocorticoid dexamethasone or possibly its phosphate or acetate salt as the active substance, further from 0.0005 to 0.1 % by weight of a preserving additive, from 0.001 to 2 % by weight of substances which keep the pH value of the medium within a range from 4.5 to 7.5, from 0.01 to 5 % by weight of substances which ensure viscosity of the medium to be within a range of 5 to 25 mPa.s, and the rest to 100 % by weight consists of distilled water. The substances which keep the pH value of the medium within a range from 4.5 to 7.5, include sodium acetate, sodium chloride, boric acid, borax, disodium edetate, sodium hydrogen phosphate or sodium dihydrogeri phosphate, alone or in a mixture. The substances which ensure viscosity of the medium to be within a range of 5 to 25 mPa.s, include hydroxypropylmethylcellulose, polyvinyl alcohol, polyoxyethylenesorbitan monooleate, alone or in a mixture.
The preserving additive is benzalkonium chloride, carbetopendecinium bromide, thimerosal, chlorohexidine or chlorobutanol.
The active substance azidamphenicol is a synthetic analogue of the wide- spectrum antibiotic chloramphenicol with identical antimicrobial spectrum. It is liposoluble, it diffuses through a bacterial membrane and it binds to ribosomes, it hinders bacterial proteosynthesis by inhibiting the peptide synthetase. At higher doses it acts bacteriostatically on a wide spectrum of microorganisms and even bactericidally on certain sensitive microorganisms. Probability of resistance is minimal. When applied topically to an eye it shows low toxicity and is well" tolerated by the eye tissue.
The second active substance is dexamethasone, a synthetic monofluorinated glucocorticoid without a mineralocorticoidal effect which is present in the form of a sodium salt. Dexamethasone shows very strong and pronounced anti-inflammatory effect, combined with an antiallergic, analgesic and antiproliferative effect.
Indications for the combined preparation according to the present solution include inflammatory processes of the eye structures where anti-inflammatory effect is required together with simultaneous suppression of arising or of a risk of arising of secondary bacterial infection.
An advantage of the eye drops according to the present solution is a simultaneous good efficiency and stability at temperatures of up to 25 °C.
Examples of embodiments
Example 1
Weighed amounts of components (according to the production batch size) are dissolved in sterilized distilled water under aseptic conditions. After having dissolved them sterilized distilled water is added to the solution up to the specified volume. The resulting solution is sterilized by filtration through a membrane filter with 0.2 μm mesh and immediately dosed into sterile vials and sealed with sterile seals under aseptic conditions. The sealed vials are labeled and packed into specified packages.
The amounts of components of a production batch are a linear function of the amounts per one package, i. e. 10 ml.
a) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g borax - 0.00100 g disodium edetate 0.00010 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g
-sterilized distilled water ad 10 ml
b) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g polysorbate 0.00100 g disodium edetate 0.00010 g polyvinyl alcohol 0.00100 g benzalkonium chloride 0.00005 g sterilized distilled water ad 10 ml
c) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium acetate 0.01000 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g chlorohexidine 0.00005 g sterilized distilled water ad 10 ml d) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g boric acid 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
e) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium hydrogen phosphate 0.01000 g sodium dihydrogen phosphate 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g chlorobutanol 0.00005 g sterilized distilled water ad 10 ml
f) Composition for one package: azidamphenicol 0.01000 g dexamethasone sodium phosphate 0.00100 g sodium chloride 0.00100 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g carbetopendecinium bromide 0.00005 g sterilized distilled water ad 10 ml
g) Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g borax 0.00100 g disodium edetate 0.00010 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml h) Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g polysorbate 0.00100 g disodium edetate 0.00010 g polyvinyl alcohol 0.00100 g benzalkonium chloride 0.00005 g sterilized distilled water ad 10 ml
i) Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium acetate 0.01000 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g chlorohexidine 0.00005 g sterilized distilled water ad 10 ml
j) Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g boric acid 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
k) . Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium hydrogen phosphate 0.01000 g sodium dihydrogen phosphate 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g chlorobutanol 0.00005 g sterilized distilled water ad 10 ml 1) Composition for one package: azidamphenicol 0.01000 g dexamethasone 0.00100 g sodium chloride 0.00100 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g carbetopendecinium bromide 0.00005 g sterilized distilled water ad 10 ml
m) Composition for one package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g borax 0.00100 g disodium edetate 0.00010 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
n) Composition for one : package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium acetate 0.01000 g boric acid 0.01000 g polysorbate 0.00100 g disodium edetate 0.00010 g polyvinyl alcohol 0.00100 g benzalkonium chloride 0.00005 g sterilized distilled water ad 10 ml
o) Composition for one package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium acetate 0.01000 g polysorbate 0.00100 g hydroxypropylmethylcellulose 0.00100 g chlorohexidine 0.00005 g sterilized distilled water ad 10 ml p) Composition for one package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g boric acid 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g thimerosal 0.00005 g sterilized distilled water ad 10 ml
q) Composition for one package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium hydrogen phosphate 0.01000 g sodium dihydrogen phosphate 0.01000 g disodium edetate 0.00010 g hydroxypropylmethylcellulose . 0.00100 g chlorobutanol 0.00005 g sterilized distilled water ad 10 ml
r) Composition for one package: azidamphenicol 0.01000 g dexamethasone acetate 0.00100 g sodium chloride 0.00100 g disodium edetate 0.00010 g hydroxypropylmethylcellulose 0.00100 g carbetopendecinium bromide 0.00005 g sterilized distilled water ad 10 ml
Example 2
Weighed amounts of components (according to the production batch size) are dissolved in sterilized distilled water under aseptic conditions. After having dissolved them sterilized distilled water is added to the solution up to the specified volume. The resulting solution is sterilized by filtration through a membrane filter with 0.2 μm mesh and immediately dosed into sterile vials and sealed with sterile seals under aseptic conditions. The sealed vials are labeled and packed into specified packages.
The amounts of components of a production batch are a linear function of the amounts per one package, i. e. 10 ml. a) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g borax 0.20000 g disodium edetate 0.02000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
b) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g polysorbate 0.50000 g disodium edetate 0.02000 g polyvinyl alcohol 0.50000 g benzalkonium chloride 0.01000 g sterilized distilled water ad 10 ml
c) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium acetate 0.20000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g chlorohexidine 0.01000 g sterilized distilled water ad 10 ml
d) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g boric acid 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml e) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium hydrogen phosphate 0.20000 g sodium dihydrogen phosphate 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g chlorobutanol 0.01000 g sterilized distilled water ad 10 ml
f) Composition for one package: azidamphenicol 0.20000 g dexamethasone sodium phosphate 0.20000 g sodium chloride 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g carbetopendecinium bromide 0.01000 g sterilized distilled water ad 10 ml
g) Composition for one package: azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g borax 0.20000 g disodium edetate 0.02000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
h) Composition for one package: azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g polysorbate 0.50000 g sodium edetate 0.02000 g polyvinyl alcohol 0.50000 g benzalkonium chloride 0.01000 g sterilized distilled water ad 10 ml i) Composition for one package: azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium acetate 0.20000 g polysorbate 0.20000 g hydroxypropylmethyl cellulose 0.20000 g chlorohexidine 0.01000 g sterilized distilled water ad 10 ml
j) Composition for one package: azidamphenicol 0.20000 g dexamethasone 0.20000 g boric acid 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
k) Composition for one package: azidamphenicol 0.20000 g dexamethasone 0.20000 g - sodium hydrogen phosphate 0.20000 g sodium dihydrogen phosphate 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g chlorobutanol 0.01000 g sterilized distilled water ad 10 ml
1) Composition for one package: azidamphenicol 0.20000 g dexamethasone 0.20000 g sodium chloride 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g carbetopendecinium bromide 0.01000 g sterilized distilled water ad 10 ml m) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g borax 0.20000 g disodium edetate 0.02000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml
n) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium acetate 0.20000 g boric acid 0.20000 g polysorbate 0.50000 g disodium edetate 0.02000 g polyvinyl alcohol 0.20000 g benzalkonium chloride 0.01000 g sterilized distilled water ad 10 ml
o) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium acetate 0.20000 g polysorbate 0.50000 g hydroxypropylmethylcellulose 0.20000 g chlorohexidine 0.01000 g sterilized distilled water ad 10 ml
p) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g boric acid 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g thimerosal 0.01000 g sterilized distilled water ad 10 ml q) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium hydrogen phosphate 0.20000 g sodium dihydrogen phosphate 0.20000 g disodium edetate 0.02000 g hydroxypiOpylmethylcellulose 0.20000 g chlorobutanol 0.01000 g sterilized distilled water ad 10 ml
r) Composition for one package: azidamphenicol 0.20000 g dexamethasone acetate 0.20000 g sodium chloride 0.20000 g disodium edetate 0.02000 g hydroxypropylmethylcellulose 0.20000 g carbetopendecinium bromide 0.01000 g sterilized distilled water ad 10 ml
Industrial applicability
The eye drops according to the present technical solution can be utilized in ophthalmology in the case of inflammatory processes of the eye structures, where combined anti-inflammatory and antibacterial treatment is useful, in particular eye inflammations which are sensitive to glucocorticoids and which are accompanied with bacterial infection or where a risk of bacterial infection of the eye exists. These are, for example, blepharocoηjunctivitis, superficial keratitis (nonpurulent, nonviral), inflammatory processes of sclera, chronical and acute allergic conjunctivitis.

Claims

PROTECTION CLAIMS
1. Ophthalmological drops with anti-inflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid, characterized in that they contain from 0.1 to 2 % by weight of azidamphenicol, from 0.01 to 1 % by weight of dexamethasone or its phosphate or acetate salts as the active substance, further from 0.0005 to 0.1 % by weight of a preserving additive, from 0.001 to 2 % by weight of substances which keep the pH value of the medium within a range from 4.5 to 7.5, from 0.01 to 5 % by weight of substances which ensure viscosity of the medium to be within a range of 5 to 25 mPa.s, and the rest to 100 % by weight consists of distilled water.
2. Ophthalmological drops according to claim 1, characterized in that the preserving additive is carbetopendecinium bromide, benzalkonium chloride, thimerosal, chlorohexidine or chlorobutanol.
3. Ophthalmological drops according to claims 1 and 2, characterized in that the substances which keep the pH value of the medium within a range from 4.5 to 7.5, include sodium acetate, sodium chloride, boric acid, borax, disodium edetate, sodium hydrogen phosphate or sodium dihydrogen phosphate, alone or in a mixture.
4. Ophthalmological drops according to claims 1, 2 and 3, characterized in that the substances which ensure viscosity of the medium to be within a range of 5 to 25 mPa.s, include hydroxypropylmethylcellulose, polyvinyl alcohol, polyoxyethylenesorbitan monooleate, alone or in a mixture.
PCT/SK2001/000018 2000-07-03 2001-06-25 Ophthalmological drops with anti-imflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid Ceased WO2002002122A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
PL01354056A PL354056A1 (en) 2000-07-03 2001-06-25 Ophthalmic drops with anti-inflammatory effects Ophthalmic drops with anti-inflammatory effects based on a broad-acting antibiotic and inflammatory based on a broad-acting antibiotic and local glucocorticoid topical glucocorticoid
UA2002031750A UA53917A (en) 2000-07-03 2001-06-25 Anti-inflammatory eye drops with broad-spectrum antibiotic and topical glucocorticoid
AU2001266548A AU2001266548A1 (en) 2000-07-03 2001-06-25 Ophthalmological drops with anti-imflammatory effect based on a wide-spectrum antibiotic and a local glucocorticoid
ROA200200235A RO121087B1 (en) 2000-07-03 2001-06-25 OPHTHALMIC EFFECTS OF PHOTOMETERS

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SKPUV0223-2000 2000-07-03
SK223-2000U SK2845U (en) 2000-07-03 2000-07-03 Ophthalmic drops with anti-inflammatory effect based on a broad-spectrum antibiotic and a local glucocorticoid

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RO (1) RO121087B1 (en)
RU (1) RU2002107305A (en)
SK (1) SK2845U (en)
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WO (1) WO2002002122A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008099210A2 (en) 2007-02-12 2008-08-21 Merck & Co., Inc. Piperazine derivatives for treatment of ad and related conditions
WO2009128057A2 (en) 2008-04-18 2009-10-22 UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al Psycho-pharmaceuticals
RU2504372C1 (en) * 2012-09-07 2014-01-20 Илья Александрович Марков Eye drops

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2506086C1 (en) * 2012-09-07 2014-02-10 Илья Александрович Марков Eye drops possessing antiinflammatory and antibacterial action

Citations (1)

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JPS56104814A (en) * 1980-01-25 1981-08-20 Kunihiro Okanoe Preparation of eye drop

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JPS56104814A (en) * 1980-01-25 1981-08-20 Kunihiro Okanoe Preparation of eye drop

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Title
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DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; OKANOUE, JOTSUNE, JAPAN: "Eye lotions containing olive oil", XP002180608, retrieved from STN Database accession no. 95:192402 CA *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; STUCHLIK, M. ET AL: "Ophthalmic drugs - some aspects of industrial manufacture", XP002180609, retrieved from STN Database accession no. 93:120358 CA *
GRINBLAT M: "CLINICAL EVALUATION OF THE TOPICAL ASSOCIATION OF DEXAMETHASONE CLOTRIMAZOLE AND AZIDOAMPHENICOL", FOLHA MEDICA, vol. 82, no. 1, 1981, pages 71 - 72, XP001024434, ISSN: 0015-5454 *
ROZVOJ FARM. RAMCI VED.-TECH. REVOLUCE, SB. PREDNASEK SJEZDU CESK. FARM. SPOL., 7TH (1979), MEETING DATE 1977, 253-6 PUBLISHER: UNIV. KARLOVA, PRAGUE, CZECH. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008099210A2 (en) 2007-02-12 2008-08-21 Merck & Co., Inc. Piperazine derivatives for treatment of ad and related conditions
WO2009128057A2 (en) 2008-04-18 2009-10-22 UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al Psycho-pharmaceuticals
RU2504372C1 (en) * 2012-09-07 2014-01-20 Илья Александрович Марков Eye drops

Also Published As

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FR2812196A3 (en) 2002-02-01
SK2845U (en) 2001-05-10
RU2002107305A (en) 2004-01-27
CZ12190U1 (en) 2002-04-15
FR2812196B3 (en) 2002-06-28
UA53917A (en) 2003-02-17
PL354056A1 (en) 2003-12-15
RO121087B1 (en) 2006-12-29
AU2001266548A1 (en) 2002-01-14

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