Ophthalmic preparation presented in form of eye drops and containing branched polyhexamethylene guanidines

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to eye drops, and aims at treating dry eye syndrome, as well as bacterial conjunctivitis and/or blepharitis. The preparation comprises a combination of the ingredients, a prolonging ingredient, additives and water. The combination of the active ingredients contains branched polyhexamethylene guanidine and sulphacetamide; the prolonging ingredient is specified in a group consisting of polyvinyl alcohol, water-soluble methyl cellulose or hydroxypropyl methyl cellulose; the additives are specified in a group consisting of a group consisting of physiologically acceptable alkaline or acid agents, and a saline tonic agent.

EFFECT: using the invention enables higher clinical effectiveness of dry eye syndrome, as well as a comorbid bacterial infection, as the preparation possesses the bactericidal effect consistent with the effect of 20% sulphacetamide causing no irritant effect on long use.

4 cl, 3 tbl, 6 ex

 

The technical field to which the invention relates.

The invention relates to ophthalmic drugs, and more specifically to eye drops that can be used for the treatment of dry eye syndrome, and bacterial conjunctivitis and/or blepharitis. The level of technology

Dry eye syndrome is a common pathological condition with different etiology. For example, it may be associated with age-related changes, wearing contact lenses, diseases of eye tissues and other Major manifestations are insufficient thickness and discontinuity in the tear film on the cornea, irritation of mucous membranes and discomfort in the eye.

In addition, the tear film is the local immune barrier. Therefore, a violation of its integrity or the reduction of thickness may cause the emergence and development of infectious diseases of the eye.

Drugs designed to fill the tear fluid with dry eye syndrome, according to a range of physico-chemical properties should be close to the natural tear fluid of a healthy person. Thus, the density should be 1,001-with 1.009 g/ml, pH is in the range of 6.0-7,8, the adhesion force of the tear film to the cornea is 30-40 Dyne/cm2and surface tension should be equal to 46 Dyne/cm2.

In the patent EP 0198490 (publ. 22.10.1986) R the hidden structures moisturizing drops on the basis of hydroxyethyl cellulose and poloxamer, containing urea as a preservative.

In the patent EP 0780121 (publ. 25.06.1997) disclosed are compounds of eye drops containing polyacrylic acid and polyvinylpyrrolidone, and benzalkonium salt as a preservative.

In the patent EP 0342297 (publ. 23.11.1989) disclosed an aqueous solution having a low surface tension, forming a continuous wetted by water absorbed layer on the hydrophobic surface, comprising partially hydrolyzed polyvinyl acetate in combination with polyvinyl alcohol. The composition of the solution also includes dextran, kollidon, citrate-phosphate buffer solution, EDTA, sodium chloride, calcium and chlorbutanol as preservative.

A common shortcoming of these solutions is the presence of allergenic preservative effect and damaging effects on soft contact lenses due to the high reactivity of these molecules (the article Systems of care for contact lenses. / Nbein, Menshikova, Avestha, Lauramine // pharmaceutical journal, 2001, t.35, No. 2).

It is known the use of sulfacetamide as an active ingredient of eye drops for the treatment of diseases of bacterial etiology (conjunctivitis, blepharitis, chlamydial and gonococcal infections) in infants, children and adults. Used drugs are effective when sod is the neigh 10-30%, for example, "Sulfatsil-sodium, 20% solution"that often causes severe irritation of the mucous membranes of the eyes, leading to the impossibility of further use.

The closest the authors consider the invention, disclosed in the patent RU 2241444 (publ. 10.12.2004)providing drops to treat dry eye syndrome, containing a lubricant, preservative, phosphate buffer, sodium chloride, purified water, characterized in that they contain as preservatives, guanidine phosphate, kollidon VA 64 as a lubricant in the following ratio of components (in wt.%):

the guanidine phosphate0,04-0,1
sodium phosphate one-deputizing0,1-0,2
sodium phosphate disubstitutedof 0.2-0.3
sodium chloride0,5-0,7
kollidon VA 64of 3.0-3.5
purified waterto 100.0

The disadvantage of analog is weak bactericidal action.

There is therefore a need for new hydrating, bacteriostatic and/or bacteria is innych tools for the treatment of dry eye syndrome and struggle with its consequences, especially with the development of bacterial infections. Disclosure of inventions

The aim of the invention is to expand the Arsenal of medicines by creating effective combined preparation for the treatment of dry eye syndrome and concomitant bacterial infection.

The technical result is the drug with bactericidal activity, comparable with the effect of a 20% solution of sulfacetamide ("Sulfatsil-sodium"), while not having irritation with prolonged use.

As a result of studies, the inventors have found that the disadvantages of the known prior art can be overcome by the creation of an ophthalmic preparation in the form of droplets containing a combination of active components, prolonging component, auxiliary substances and water, in which the combination of active components composed of branched, guanidine of the formula (I)

where R representsor,

n1n2and n3equal 1-3, a z is equal to 0.15-1,10 molecular weight distribution Mw/Mnfrom 5.4 to 9.3 when the mass-average molecular mass Mwin the range of from about 3800 to 6300 and srednetsenovoj molecular mass Mnin the interval from priblizitelen the 600 to 1100, present in the form of hydrochloride, and sulfacetamide;

prolonging component selected from the group consisting of polyvinyl alcohol, water-soluble methyl cellulose or hydroxypropylmethylcellulose, copolymer of vinylpyrrolidone/vinyl acetate, and copolymer based on N-vinylpyrrolidone General formula (II)

,

where Monomeric link M is the fragment of 2-methyl-5-vinyltetrazole (MW) or 2-methyl-5-vinylpyridine) - derivatives (IMP)

,

and the content of monomer units n is 25-50 mole.%, srednevozrastnoe molecular mass Mµthe copolymer depends on the nature of M: if M is MW, Mµ=30-50 kDa; if M is a profit center, then Mµ=15-40 kDa

with the following content of components (in wt.%):

hydrochloride, guanidine0,03-0,5
sulfacetamide2,0-5,0
prolonging componentof 0.05 to 3.5;

excipients selected from the group consisting of physiologically portable alkaline or acid agents present in amounts required to maintain the pH of the preparations is in the range from 6.0 to 7.8,, and salt tonic agent selected from physiologically-tolerated salts of sodium or potassium and mixtures thereof, present in an amount to provide toychest drug comparable to onicescu natural tear fluid of a healthy person.

Physiologically tolerated alkaline or acid agents can be appropriately selected from alkalis, such as sodium hydroxide or potassium hydroxide, acids such as hydrochloric acid, phosphoric acid, citric acid, succinic acid and salts undergo hydrolysis in aqueous solutions, such as sodium phosphate, sodium dihydrophosphate, sodium citrate. The choice of a suitable alkaline or acidic agent and determination of the required number can be easily performed by a person skilled in the art, without going beyond the common knowledge and, if necessary, by routine experiment.

Salt tonic agent may be selected from sodium chloride or potassium chloride, and can be theoretically evaluated by a specialist in this field on the basis of common knowledge and experimentally clarified during a routine experiment, for example by determining the osmolality of the obtained ophthalmic drug.

Hydrochloride, guanidine (phmg-GC) of the formula (I) is a 4th class that is lichnosti, ie is not dangerous to the human body, he has a strong microbicidal effect against major pathogens of infectious eye diseases: Escherichia coli, Staphylococcus, Streptococcus, Candida, Proteus.

Efficiency pgmg-GC relative to the listed strains, determined by the serial dilution method with a nutrient medium and measured the minimum inhibitory concentration ranges from 1.0 to 300 μg/ml, thus, the minimum bacteriostatic concentration pgmg-GC is 0.01%. To achieve a bactericidal effect can be used in concentrations up to 0.5%. Sulfacetamide is low toxic compound, as evidenced by its use in children, particularly infants infants.

Transparency is a natural demand for optical media. Therefore, the choice of prolonging component should be made taking into account the requirements of transparency at a corresponding toychest of the drug. The model can serve as an isotonic solution of sodium chloride containing the maximum concentration pgmg-GC. Polymers, physico-chemically compatible with saline G-pgmg andproviding compositions, similar in viscosity to the lacrimal fluid (1,2-1,4), suitable for use in accordance with the invention. These are polyvinyl alcohol, copolym the R vinylpyrrolidone/vinyl acetate in a molar ratio of 6:4 (concentration of 3-3,5%) and water-soluble methylcellulose with a molecular mass of about 20 kDa (concentration of 0.05-0.1%), and copolymer based on N-vinylpyrrolidone General formula (II)above.

Other important requirements to solutions intended for instillation into the conjunctival cavity, are sterility, isotonicity, pH value close to the natural, and duration.

Sterility is necessary to ensure long-term storage of the drug prior to implementation, as well as guarantee the absence of pathogenic microorganisms in the product after opening the package during use. Isotonicity and close to the natural pH create a comfortable environment for the cells of the conjunctiva, which excludes them from damage and discomfort (feeling pain or burning sensation in the eye). The duration of action can reduce the number of instillation, which reduces drug burden and makes it possible for long-term use of the drug without side effects.

The person skilled in the art obvious theoretical and experimental methods for evaluation of concentrations of components in the preparations of this type. The most famous are theoretical calculation taking into account isotonic equivalents and geometria supercooling the mixture of salt/ice.

An additional advantage of the preparation according to the invention is its suitability for use in accordance with the s 3 years, that is confirmed by the comparison of physico-chemical and microbiological indicators vegetativnogo drug and drug after storage. The pH, surface tension, electrical resistivity and refractive index for use after storage statistically significantly (p<0,05) did not differ from the original values.

The retention time of the drug on the cornea can be indirectly assessed by the severity of bacteriostatic or bactericidal action. Evaluation of retention time is the time after which growth of the microorganism colony at bacteriostatic concentrations (0.01 to 0.05%) or time before which there is no growth of colonies of the microorganism at bactericidal concentrations (0.1 to 0.5%) seeded sample of tear fluid on an appropriate nutrient medium. Studies have shown that the greatest retention time of the drug (8-9 hours) is achieved with the use of methylcellulose or hydroxypropylmethylcellulose as prolonging agent. The product containing polyvinyl alcohol or copolymer of vinylpyrrolidone/vinyl acetate, held during 6-7 hours.

The achievement of the technical result of the invention is proved by the results obtained in the preferred examples of its implementation.

The implementation of the image is possible

Preparation of medicines in accordance with the invention and evaluation of their pharmacological characteristics illustrated in the following examples.

Example 1. Drops for the treatment of dry eye syndrome with bacteriostatic action

Under aseptic conditions in a glass apparatus with a stirrer, thermometer and heated jacket is placed in 45 ml of hot pyrogen-free water and successively dissolved therein 0.05 g of hydrochloride, guanidine of the formula (I), 2.00 g sulfacetamide, 0.10 g of sodium dihydrophosphate, 0.25 g of sodium hydrogen phosphate and 0.50 g of sodium chloride.

In the second similar apparatus in 50 ml of water was dissolved 3.0 g prolonging agent (methylcellulose). The solutions are mixed in a pre-weighed aseptic containers, which add water to 100.00 g

Sterilization of the solution is carried out at 120°C for 8-12 minutes. After sterilization of the finished drug portions of 2 ml Packed in a sterile dropper polyethylene high-pressure supply screw-on lids and placed in boxes with the information necessary for the identification and application.

Example 2. Drops for the treatment of dry eye syndrome with bactericidal action

Preparation of droplets carried out analogously to example 1, using 0.20 g of hydrochloride

the guanidine of the formula (I), 5,00 g sulfacet the Ministry of foreign Affairs 0.15 g of sodium dihydrophosphate, of 0.85 g of sodium hydrogen phosphate, 0.3 g of sodium chloride and 2.0 g of hydroxypropylmethylcellulose as prolonging agent.

Example 3. Drops for the treatment of dry eye syndrome with pronounced bactericidal

Under aseptic conditions in a glass apparatus with a stirrer, thermometer and heated jacket is placed in 45 ml of pyrogen-free water and successively dissolved therein 0.50 g of hydrochloride, guanidine of the formula (I), 5,00 g sulfacetamide and 0.70 g of sodium chloride, stirred until dissolved, and add hydrochloric acid to a pH of 6.5 (approximately 0.4 g in terms of hydrogen chloride).

In the second similar apparatus in 50 ml of pyrogen-free 0,60 g-prolonging agent (polyvinyl alcohol). The solutions are mixed in a pre-weighed aseptic capacity to work under pressure or under vacuum, after which water is added to the mass of the solution 100,00,

After obtaining a clear solution is sterilized resulting solution by filtration through a membrane filter with shut-off capacity of 0.2 μm, taking his second aseptic tank, which create and maintain the required vacuum.

After sterilization of the finished drug portions of 2 ml Packed in a sterile dropper polyethylene high-pressure supply Navi is chiweenie lids and placed in boxes with the information, necessary for the identification and application.

Example 4. The definition of the spectrum bactericidal efficacy in vitro and minimum bacteriostatic (overwhelming growth) concentration (MBC)

Spectrum bactericidal efficacy in the experience of in vitro characterized by suspension polymerization in accordance with the guidance of R. 4.2.2643-10 "laboratory Methods of research and testing of disinfectants to assess their effectiveness and safety. Explore 0.05% solution of hydrochloride, guanidine of the formula (I) (G-pgmg), a 20% solution of sulfacetamide ("Sulfatsil-sodium", JSC "Sintez", Kurgan) and the drug is prepared in accordance with example 2 of the invention.

The minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations determined by micromethods serial twofold dilutions in medium Mueller-Hinton (Oxoid) in accordance with the normative document "guidelines for determining the sensitivity of microorganisms to antibiotics" (MUK 4.2 1890-04).

Preparations with a concentration of active ingredient 1000 μg/ml, prepared in pyrogen-free distilled water, diluted to 128 µg/ml of culture medium. Studies performed in 96-well tablets for immunological studies. Prepare a series of twofold dilutions of the study drug is in the environment II Mueller-Hinton (Oxoid) in a volume of 50 μl. For microorganisms, poorly growing on ordinary nutrient media, in the above medium was added 5% defibrinating sheep blood.

The inoculate bacterial cultures from isolated colonies are prepared in the form of a suspension according to the standard turbidity of Mcfarland (0,5) in physiological solution. The suspension is diluted in the environment II Mueller-Hinton concentrations up to 108CFU/ml of the Prepared suspension contribute to the wells of plates (50 μl/well) and prepare a dilution in the concentration range from 128 to 0,0003 mg/ml Inoculated tablets incubated for 18 hours at 37°C. the Lowest concentration of the study drug, at which no visible growth of microorganisms, is an estimate of the IPC.

To determine the IPC Candida albicans isolated from colonies of preparing a suspension in a nutrient medium Saburo standard turbidity of Mcfarland (0,5), which corresponds to 106CFU/ml for fungal cultures. A series of twofold dilutions of the drugs are prepared in an environment Saburo in a volume of 100 ml After inoculation of yeast tablets incubated for 48 hours at 30°C. a Series of twofold dilutions of the drugs are prepared in an environment Saburo in a volume of 100 ml. the Results are presented in table 1.

Table 1
The microorganism (Strain) Pgmg-GCSulfacetamideMedication
Escherichia coli (ATSS 27952)2,0128128
Proteus mirabilis (5)1,06432
Staphylococcus aureus (ATCC29213, sensitive to methicillin)2,03232
Staphylococcus aureus (ATSS 43300 methicillin-resistant)2,03232
Candida albicans (ATSS 24433)4,0>128128
Pseudomonas aeruginosa (ATSS 27853)4,0>128128
Streptococcus oralis (1105007)1,06464
Streptococcus pyogenes (151023)2,0>128128
Streptococcus salivarious (11051007) 0,063>128128

Example 5. Determination of minimum bactericidal (MBC) concentrations

Explore 0.2% solution of hydrochloride, guanidine of the formula (I) (G-pgmg), a 20% solution of sulfacetamide ("Sulfatsil-sodium", JSC "Sintez", Kurgan) and the drug is prepared in accordance with example 1 of the invention.

Determination of the bactericidal efficacy against microorganisms is carried out in a suspension containing 109CFU/ml In the culture of microorganisms (Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Streptococcus oralis) in the amount of 0.5 ml contribute to 4.5 ml of the preparations, mixed and incubated for the desired time of induction (tHIW,). From a mixture of selected 0.5 ml and transferred to a neutralizing solution containing 1% lauryl sulphate with 10% skim milk, and then mix and leave for 5 minutes.

After this time, 0.5 ml of the neutralized culture transferred to 4.5 ml of sterile water. After mixing, 0.1 ml of the suspension was transferred into 5 ml of liquid nutrient medium and on the surface of agar medium (agar liquid medium Saburo for Candida albicans and environment MCS for the other strains). Counting colonies carried out after 24 hours of incubation for Candida albicans and after 48 hours of incubation for the rest. The results are shown in table 2.

Table 2
The microorganism (Strain)MINPgmg-GCSulfatsil-sodiumMedication
Escherichia coli (ATSS 27952)102,70>128128
Proteus mirabilis (5)21,03216
Candida albicans (ATSS 24433)54,0>12864
Staphylococcus aureus (ATCC43300)21,03232
Pseudomonas aeruginosa (ATCC 27853)24,0>128128
Streptococcus oralis (1105007)21,0>128128
Streptococcus pyogenes (151023) 24,0>128128
Streptococcus salivarious (11051007)20,125>1216

The obtained data show that the drug in accordance with the invention is effective against most of the tested strains to the same extent that "Sulfatsil-sodium", which confirms the achievement of the technical result of the invention.

Example 6. Treatment of dry eye syndrome in dogs Efficacy of treatment of dry eye syndrome in dogs appreciate the stability of the tear film (sample for Norn (M.S. Norn, 1969) and the production of tear fluid. In accordance with the study Protocol in the lower conjunctival SAC instilliruut 1 drop of 0.2% fluorescein-sodium, and then determine the time from the last blink to the appearance in tinted tear film break in the form of black spots or cracks on the surface of the cornea. The time of the destruction of the tear film is an important indicator of its stability. The results were evaluated as follows:

more than 10 seconds the norm;

5-10 seconds is less than the norm;

less than 5 seconds sharp decrease in the stability of the tear film.

The results are presented in table 3.

Table 3
AnimalsThe time of the destruction of the lacrimal film,
Before the treatmentAfter 2 weeks
Terrier38
Poodle712
Spaniel615
Spaniel710
Pekingese49

Thus, 2 weeks after treatment was eliminated purulent conjunctivitis, animals disappeared painful spasm of the eyelids and photophobia. Selection tears almost normalized.

1. Ophthalmic drug in the form of droplets containing a combination of active components, prolonging component, auxiliary substances and water, wherein the combination of active components composed of branched, guanidine of the formula (I)
where R representsor n1n2and n3equal 1-3, a z is equal to 0.15-1,10 molecular weight distribution Mw/Mnfrom 5.4 to 9.3 when the mass-average molecular mass Mwin the range of from about 3800 to 6300 and srednetsenovoj molecular mass Mnin the range of from about 600 to 1100, present in the form of hydrochloride, and sulfacetamide,
prolonging component selected from the group consisting of polyvinyl alcohol, water-soluble methyl cellulose or hydroxypropylmethylcellulose, copolymer of vinylpyrrolidone/vinyl acetate, and copolymer based on N-vinylpyrrolidone General formula (II):

where Monomeric link M is the fragment of 2-methyl-5-vinyltetrazole (MW) or 2-methyl-5-vinylpyridine) - derivatives (IMP):

and the content of monomer units n is 25 to 50 mol.%, srednevozrastnoe molecular mass Mµthe copolymer depends on the nature of M: if M is MW, Mµ=30-50 kDa; if M is a profit center, then M=15-40 kDa
with the following content, wt.%:

hydrochloride, guanidine0,03-0,5
sulfacetamide1,0-5,0
prolonging componentof 0.05 to 3.5;

excipients selected from the group consisting of physiologically portable alkaline or acid agents present in amounts required to maintain the pH of the preparation is in the range from 6.5 to 8.0, and salt tonic agent selected from physiologically-tolerated salts of sodium or potassium and mixtures thereof, present in an amount to provide toychest drug comparable to onicescu natural tear fluid of a healthy person.

2. Ophthalmic preparation according to claim 1, characterized in that it has a composition, wt.%:

hydrochloride, guanidine0,05
sulfacetamide2,0
of sodium dihydrophosphate0,10
hydrogen phosphate sodium0,25
sodium chloride0,5
the methylcellulose3,0
pyrogen-free waterto 100.0

3. Ophthalmic preparation according to claim 1, characterized in that the n has a composition, wt.%:

hydrochloride, guanidine0,2
sulfacetamide5,0
of sodium dihydrophosphate0,15
hydrogen phosphate sodium0,85
sodium chloride0,3
the hypromellose2,0
pyrogen-free waterto 100.0

4. Ophthalmic preparation according to claim 1, characterized in that it has a composition, wt.%:

hydrochloride, guanidine0,5
sulfacetamide5,0
hydrochloric acid (in terms of HCl)0,4
sodium chloride0,7
polyvinyl alcohol : 0,6
pyrogen-free waterto 100.0



 

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58 cl, 4 ex, 6 tbl, 5 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacology, pharmaceutics and medicine, more specifically to a new generation of high-stable dosage forms prepared with using the process of sublimation in a specific mode with a composition containing no stabilising agents reducing the width of therapeutic action of finished dosage form substantially. The invention concerns the pharmaceutical composition for injections and infusions containing 3-oxy- and methylpyridine derivatives and pharmaceutically acceptable salts thereof as an active ingredient, sodium chloride or potassium chloride as an additive agent, in the form a lyophilisate. The process involves the sublimation followed by the vacuum dewatering for at least 64 hours.

EFFECT: pharmaceutical composition possesses high stability for the whole shelf-life as opposed to all known pharmaceutical formulations of these compounds; it preserves pharmacological activity and enables dissolving the composition immediately before use and reducing a risk of the negative effect of the thermal sterilisation of aqueous solutions.

2 cl, 7 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine. A pharmaceutical formulation for the treating diseases associated with endothelial dysfunction contains an active ingredient presented by a methyl pyridine derivative - 1.0-6.0 wt %; purine - 10.0-80.0 wt % and additive agents - the rest. The active substance is presented by compounds of a group: 3 -(N,N-dimethyl carbamoyloxy)-2-ethyl-6-methylpyridinium succinate, 3-methylpyridinium succinate, 2-ethyl-6-methyl-3-hydroxypyridinium hydrochloride, 6-trichloromethyl-2-chloropyridine (nitrapyrin), 2-ethyl-6-methyl-3-hydroxypyridine succinate. Purine is presented by inosine, adenosine, hypoxanthine. The pharmaceutical formulation may be presented in the form of injections, lyophilisate, solid capsules, tablets and suppositories.

EFFECT: formulation according to the invention provides creating the stable drug dosage form which considerably exceeds the existing analogues in pharmacodynamics activity on the endothelial dysfunction and toxicological properties.

4 cl, 4 tbl, 9 ex

Eye drops // 2504372

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to eye drops that contain 1-3 wt % of taurine, 0.01-0.1 wt % of dexamethasone, 0.4-0.6 wt % of boric acid, 0.4-0.6 wt % of hydroxypropyl methyl cellulose and water. The eye drops aim at treating various eye diseases related to metabolic disturbance in eye tissues, and inflammatory injury of an eye surface.

EFFECT: higher therapeutic efficacy of the eye drops.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents pharmaceutical composition for treating gastroesophageal reflux disease, containing at least one proton pump inhibitor and at least one probiotic, wherein the proton pump inhibitor is taken in the amount of 0.05-25 wt % in the composition; and the probiotic is taken in the amount of 10-95 wt %; additive agents up to 100 wt %.

EFFECT: provided preventing Hpylori translocation, avoiding the necessity of Hpylori detection and antibacterial course of eradication, higher safety of the prolonged therapy with the proton pump inhibitors and avoided gastric mucosa atrophy, and a risk of gastric cancer.

5 cl, 10 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to ophthalmic preparations presented in the form of eye drops and applicable for treating dry eye syndrome and bacterial conjunctivitis. The preparation contains polyhexamethylene guanidine that is presented by branched oligomers in the form of hydrochloride; besides, phosphate buffered saline, poly(N-vinylpyrrolidone) and water are the ingredients.

EFFECT: using the invention provides the higher clinical effectiveness in dry eye syndrome, as well as potential comorbid bacterial infection whereas the declared preparation has no irritant effect if used for a long period of time.

3 cl, 2 tbl, 3 ex

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