RU2508123C1 - Pharmaceutical composition for local application in treating inflammatory eye diseases and method for using it - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and chemical-pharmaceutical industry. The group of inventions refers to pharmaceutical composition for local application and containing an active ingredient presented by superoxide dismutase as a part of cross-linked methoxy-poly(ethylene glycol)-poly(L-lysine) block copolymer nanoparticles, as well as to a method of treating inflammatory eye diseases using the given pharmaceutical compositions. The active ingredient content in the composition makes 50-500 kUnit/ml. The composition can be presented in the form of eye drops or a spray. In addition, the composition contain antibiotics, steroids, adrenoreceptor blocking agents, macro- and microelements, and vitamins.

EFFECT: group of inventions provides the intensified and prolonged anti-inflammatory action of superoxide dismutase on the eye diseases related to inflammatory processes.

7 cl, 1 dwg

Description

The invention relates to topical drugs for the treatment of inflammatory eye diseases, in particular to compounds intended for use in the pharmaceutical industry, and relates to a pharmaceutical composition containing, as an active ingredient, a superoxide dismutase enzyme included in a carrier in the form of nanoparticles and target additives .

The invention uses the following terminology adopted in this area, as well as abbreviations:

Superoxide dismutase (SOD, EC 1.15.1.1) belongs to the group of antioxidant enzymes. This enzyme consists of two subunits containing one atom of zinc and copper, with a total mass of 32 kDa. Superoxide dismutase catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide by the following reaction:

2O ₂ ^- + 2H ⁺ → O ₂ + H ₂ O ₂

A carrier in the form of nanoparticles based on a crosslinked methoxy-poly (ethylene glycol) -poly (L-lysine) block copolymer [US Patent No. 0291065 A1]. Inflammatory eye diseases: Inflammatory eye diseases include keratitis (inflammation of the cornea) and uveitis of various etiologies, retinitis, consequences of injuries (burns, mechanical, surgical), infectious processes.

Antioxidant. Antioxidants - oxidation inhibitors, substances that can slow down oxidation. This is a group of biologically active compounds that neutralize free radicals in the body - unstable atoms and compounds that are formed during normal metabolism and are present in the environment, but, accumulating excessively, become dangerous. Antioxidants protect cell membranes from harmful effects or reactions that can cause excessive oxidation in the body.

Installation. Installation - drip administration of drug solutions.

OS is the left eye.

OD is the right eye.

It is known that in inflammatory diseases of the eye, a significant role is played by free radical processes associated with either an increase in the formation of free radicals, or with the depletion of a pool of endogenous antioxidants, and oxidative stress. Moreover, free radicals damage structural and functional cellular components, promote the formation of toxic substances, exacerbate microcirculation disorders in tissues, leading to tissue ischemia, [Carubelli R., Nodrquist R.E., Rowsey J.J. Role of active oxygen species in comeal ulceration. Effect of hydrogen peroxide generated in situ. (1990) Cornea, 9, 161-169. Yadav U.C.S., Kalariya N.M., Ramana K.V. Emerging role of antioxidants in the protection of uveitis complications. (2011) Curr. Med. Chem., 18, 931-942]. Inflammatory diseases include keratitis (inflammation of the cornea) and uveitis of various etiologies, retinitis, the consequences of injuries (burns, mechanical, surgical), and infectious processes. In the complex medical treatment of inflammatory eye diseases, non-specific anti-inflammatory drugs (antibiotics and corticosteroids), antiproteolytic drugs, antioxidants, antihypoxants, agents that have a regenerative effect and improve microcirculation are used [Rational Pharmacotherapy in Ophthalmology (2006) (ed. E.A. Egorov) , Litterra Publishing House, Moscow, p. 652-657. Morozov V.I., Yakovlev A.A. (2009) Pharmacotherapy of eye diseases, MEDpress-Inform Publishing House, Moscow, p. 169-179].

As antioxidant agents used in inflammatory processes in the eye, emoxipin, pyridoxine [Arkhipova L.T., Dolgova I.G. The prognostic significance of local and systemic indicators of lipid peroxidation and antioxidant system in penetrating eye injuries and their dynamics against the background of local use of antioxidants. (2001) News, ophthalmos. No. 5, 37-40], echinochrome ("Histochrome") [Patent RU 2038088 C1].

The promising use of superoxide dismutase preparations for uveitis was noted [de Kozak Y., Nordman J.P., Faure J.P., Rao N.A., Marak G.E. Effect of antioxidanr enzymes on experimental uveitis in rats. (1989) Ophtalmic. Res., 21, 230-234. Yamada M., Shichi H., Yuasa T., Tanouchi Y., Mimura Y. Superoxide in ocular inflammation: human and experimental uveitis. (1986) J. Free Radio. Biol. Med., 2, 111-117], as well as in case of alkali damage to the eye [Alio J.L., Ayala M.J., Mulet M.E., Artola A., Ruiz J.M., Bellot J. Antioxidant therapy in the treatment of experimental acute comeal inflammation. (1995) Ophtalmic. Res., 27, 136-143].

The disadvantage of the drugs is the lack of penetration of drug compounds into the tissues of the eye, since they need to overcome the corneal barrier, which consists of three layers: epithelial, stroma and endothelial. In addition, the drug is easily washed off by a tear from the surface of the eye. Usually only about 5% of the substance used penetrates the cornea and reaches the intraocular tissues [Ahmad I., Patton T. Importance of the noncomeal absorption route in topical ophthalmic drug delivery. (1985) Invest. Ophtalm. Vis Sci., 26, 584-587].

This problem is usually solved by increasing the concentration of the drug substance in the drug. However, an increase in the content of the active compound can cause allergic reactions, as well as undesirable local and systemic side effects associated with the entry of these drugs into the bloodstream.

A promising approach to solving the problem of drug delivery to intraocular tissues is the use of nanoparticles as drug delivery systems, since they significantly increase the bioavailability of the drug and allow the creation of the necessary concentration of drug substance in the tissues [Sahoo SK, Dilnawaz F., Krishnakumar S. Nanotechnology in ocular dmg delivery (2008) Drug Discov. Today, 13, 144-151. Araujo J., Gonzalez E., Egea M.A., Garcia M.L., Souto E.B. Nanomedicines for ocular NSAIDs: safety on drug delivery (2009) Nanomedicine, 5, 394-401]. Positive results have been obtained from experimental studies on the inclusion of a number of drugs, such as steroids, in nanocarriers [Gomez-Gaete C., Tsapis N., Besnard M., Bochot A., Fattal E. Encapsulation of dexamethasone into biodegradable polymeric nanoparticles (2007) Int. J. Phar., 331, 153-159], carbonic anhydrase inhibitor [Zhang X., Yaun W., Zhau D., Wu J. Lyceum Chinense and calcium phosphate nanoparticles for ophthalmic drug delivery (2008) Nanotech., 2, 401- 404], cyclosporin A [Patent US 0020336 A1].

However, there are currently no pharmaceutical preparations in the composition of nanoparticles for topical application in inflammatory eye diseases. Local use of drugs is most preferred for patients, as they can use them on their own.

Currently, Erisod [Patent RU 2144343 C1] and Rexod [Rexod, preparations for use, registration certificate LSR-006689 / 10-150710], the active principle of which is superoxide dismutase, are produced in our country. Drugs are used, including by instillation into the conjunctival cavities of the eyes.

Indications for use of these drugs are open-angle glaucoma, anterior uveitis, secondary keratopathies, herpetic and adenoviral eye lesions, injuries and burns to the eyes. We selected Erisod as a prototype of the claimed group of inventions. This remedy in the treatment of inflammation is characterized by all of the above disadvantages in the form of the impossibility of creating the required concentration of the active substance in the tissues of the eye.

We found that the superoxide dismutase enzyme included in the composition of nanoparticles eliminates the noted drawbacks.

Similar preparations, which are complexes of enzymes with synthetic polymers having nanoparticle sizes, have been proposed for the delivery of therapeutic agents, primarily in the treatment of diseases of the central nervous system [Patent US 0291065 A1]. For experimental studies, we used aqueous solutions of a preparation containing superoxide dismutase included in the composition of nanoparticles based on a crosslinked methoxy-poly (ethylene glycol) -poly (L-lysine) block copolymer obtained according to the method of [Patent US 0291065 A1], and target additives.

The technical result of the claimed pharmaceutical composition for topical application in the treatment of inflammatory eye diseases and the method of its use is to enhance the anti-inflammatory therapeutic effect of superoxide dismutase, which is expressed in reducing the healing time of inflammation, prolonging the effect of reducing the manifestations of the inflammatory process with a decrease in the risk of local and general adverse reactions. It has been shown that the use of the claimed pharmaceutical composition leads to a significant reduction in the time of corneal edema, a decrease in conjunctival hyperemia, a decrease in eyelid edema, a decrease in fibrinous deposits during experimental uveitis, and an increase in antioxidant activity in the lacrimal fluid during alkaline burns of the cornea of experimental animals.

This technical result in terms of the pharmaceutical composition is achieved in that the pharmaceutical composition for topical application in inflammatory eye diseases contains an effective amount of an active substance that is a superoxide dismutase incorporated into nanoparticles based on crosslinked methoxy-poly (ethylene glycol) -poly (L-lysine) block copolymer, and targeted additives.

Preferably, in the pharmaceutical composition, an effective anti-inflammatory concentration of superoxide dismutase is 50-500 kU / ml.

Preferably, the pharmaceutical composition is in the form of eye drops or a spray.

Preferably, either a buffering agent and / or 0.15 M sodium chloride are used as target additives in the pharmaceutical composition.

Preferably, the pharmaceutical composition contains a preservative.

Preferably, the pharmaceutical composition additionally contains preparations selected from the groups: or antibiotics, or steroids, or adrenergic blocking agents, or vitamins, or macro and micronutrients.

This technical result in terms of a method of treating inflammatory eye diseases is achieved by instillation into the conjunctival cavity of the eye of the pharmaceutical composition according to claim 1-7, containing an effective amount of superoxide dismutase in a dose of from 1.5 to 15 kU daily 2-3 times a day, lasting from 1 week until the end of the inflammatory process.

The invention is illustrated in figure 1., which shows the effect of superoxide dismutase and the claimed pharmaceutical composition on antioxidant activity in the lacrimal fluid of rabbits after an alkaline burn of the cornea. Antioxidant activity as a percentage of the initial in the tear fluid: o - rabbit No. 16 (untreated); ■ - rabbit No. 17 (treatment with the claimed pharmaceutical composition); ♦ - rabbit No. 18 (treatment with superoxide dismutase).

A pharmaceutical composition for topical application in inflammatory eye diseases is illustrated by the following examples.

Example 1

Preparation of the pharmaceutical composition of the invention

The pharmaceutical composition contains as an active substance an effective amount of superoxide dismutase incorporated into nanoparticles based on a crosslinked methoxy poly (ethylene glycol) poly (L-lysine) block copolymer according to the method of [Patent US 0291065 A1]. The resulting nanoparticles are white and are freeze-dried powder. Depending on the lyophilization conditions, the substance can be further dissolved in water or in aqueous buffer solutions or in an isotonic mixture, which may also contain a preservative.

Eye drops were prepared as follows. A 10 mg sample of the active substance was placed in a clean sterile beaker; 3.2 ml of deionized water was added. Stirred on a magnetic stirrer until completely dissolved. The solution was colorless. Then, sterile filtration of the solution was carried out through 0.22 μm Millipore filters. An effective anti-inflammatory concentration of superoxide dismutase was 500 kU / ml.

The compliance of the composition was checked by:

1. The activity of superoxide dismutase, determined by the method [Kostyuk VA, Potapovich AI, Kovaleva Zh.V. A simple and sensitive method for determining the activity of superoxide dismutase, based on the oxidation reaction of quercetin. (1990) Issues. Honey. Chemistry, 36, No. 2, 88-91]. The method is based on determining the degree of inhibition of the quercetin oxidation reaction in the presence of superoxide dismutase. The unit of activity of superoxide dismutase was taken as the amount of enzyme in 1 ml of the reaction mixture, which causes inhibition of the oxidation reaction of quercetin by 50%.

2. The pH of the solution (7.5), which was checked using a pH meter.

3. Electrophoretic mobility of the drug under conditions of non-denaturing electrophoresis in 10% polyacrylamide gel in the method [Laemmli U.K. Cleavage of structural proteins during the assembly of the head of Bacteriophage T4. (1970) Nature, 227, 680-685]. For staining proteins used Coomassie diamond blue R-250.

Example 2

The tool was prepared as described in example 1, but a portion of the active substance equal to 5 mg was dissolved in 3.2 ml of a solution of 0.15 M NaCl in deionized water containing 0.3 mg / ml benzalkonium chloride. An effective anti-inflammatory concentration of superoxide dismutase was 250 kU / ml.

Example 3

The tool was prepared as described in example 1, but a weighed portion of the active substance equal to 1 mg was dissolved in 3.2 ml of 0.05 M Hepes buffer, pH 7.5. An effective anti-inflammatory concentration of superoxide dismutase was 50 kU / ml.

Example 4

The tool was prepared as described in example 1, but a weighed portion of the active substance equal to 1 mg was dissolved in 3.2 ml of 0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl and 1 mg / ml benzalkonium chloride . An effective anti-inflammatory concentration of superoxide dismutase was 50 kU / ml.

The study of the anti-inflammatory activity of the claimed pharmaceutical composition and the implementation of the method

Modeling experimental immunogenic uveitis in rabbits.

The experiment involved rabbits of the chinchilla breed weighing 2-2.5 kg. Work with experimental animals was carried out in accordance with the provisions of the Helsinki Declaration. Animals were kept under standard conditions. In animals, immunogenic uveitis was reproduced according to the method [Neroev V.V., Davydova G.A., Perova T.S. Modeling of immunogenic uveitis in rabbits. (2006) Bull. Experiment. Biol. Honey. 142, 598-600]. For rabbits in Examples 5-16, normal horse serum was injected subcutaneously in an amount of 5 ml to reproduce immunogenic uveitis, then 10 days after subcutaneous injection, a resolving dose of serum in an amount of 70 μl was intravitreally injected into both eyes.

Clinical signs of intraocular inflammation were evaluated by sequential analysis of data from an external examination of the eye, biomicroscopy, ophthalmoscopy.

Clinical manifestations of uveitis (conjunctival edema, conjunctival hyperemia, corneal edema, fibrinous deposits in the anterior chamber) were assessed using conditional scores on a four-point scale: no sign — 0, mild manifestations — 1, moderate — 2, severe — 3.

Example 5

Rabbit number 12. Placebo instillation (0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl) in both eyes (OS and OD) 3 times a day for 30 μl was performed on a rabbit with immunogenic uveitis.

The clinical manifestation of uveitis - corneal edema - was assessed in conditional scores on a four-point scale: the absence of a sign - 0, the manifestations of a weak degree - 1, medium - 2, strong - 3.

3 day 4 day 5 day 8 day OD one 2 2 3 OS one 2 2 3

Instillations of the buffer solution in both eyes of rabbit No. 12 did not lead to a decrease in corneal edema. Edema progressed, the cornea became more cloudy.

Example 6

Rabbit number 3. The superoxide dismutase solution was instilled at a concentration of 50 kU / ml in a 0.15 M NaCl solution, pH 7.5, 30 μl in both eyes 3 times a day.

The degree of corneal edema was determined as in Example 5.

3 day 4 day 5 day 8 day OD one 2 2 one OS one one 0 0

In rabbit No. 3, instillation of a superoxide dismutase solution led to a decrease in corneal edema, which almost subsided by the 8th day.

Example 7

Rabbit number 7. A solution of the claimed pharmaceutical composition was installed at a concentration of 1 mg / ml (50 kU / ml) in 0.05 M Hepes buffer, pH 7.5, 30 μl in both eyes 3 times a day.

The degree of corneal edema was determined as in Example 5.

3 day 4 day 5 day 8 day OD 0 one 0 0 OS one 0 0 0

In rabbit No. 7, the installation of a solution of the claimed pharmaceutical composition led to the fact that corneal edema was practically not observed and finally disappeared on the 5th day.

Example 8

Rabbit number 10. Placebo installations (0.05 M phosphate buffer, pH 7.5 containing 0.15 M NaCl) were performed in both eyes (OS and OD) 3 times a day for 30 μl.

The clinical manifestation of uveitis - conjunctival hyperemia - was assessed in conditional scores on a four-point scale: absence of a sign - 0, manifestations of a weak degree - 1, medium - 2, strong - 3.

3 day 4 day 5 day 8 day OD 2 3 3 2 OS 2 3 3 2

Placebo installations in both eyes of rabbit No. 10 did not lead to a decrease in conjunctival hyperemia. Hyperemia was pronounced and only slightly decreased by the 8th day.

Example 9

Rabbit number 1. Superoxide dismutase was instilled at a concentration of 250 kU / ml in a 0.15 M NaCl solution, pH 7.5, in both eyes 3 times a day for 30 μl.

The degree of conjunctival hyperemia was determined as in example 8.

3 day 4 day 5 day 8 day OD 2 2 one 0 OS 2 one one 0

Instillations of a superoxide dismutase solution in both eyes of rabbit No. 1 reduced the severity of conjunctival hyperemia. On the 8th day, hyperemia was not observed.

Example 10

Rabbit number 5. An instillation of a solution of the claimed pharmaceutical composition at a concentration of 5 mg / ml (250 kU / ml) in a 0.15 M NaCl solution, pH 7.5, containing 0.3 mg / ml benzalkonium chloride was carried out in both eyes 3 times a day for 30 μl

The degree of conjunctival hyperemia was determined as in example 8.

3 day 4 day 5 day 8 day OD one one one 0 OS one one one 0

Instillations of the claimed pharmaceutical composition in both eyes of rabbit No. 5 led to a more pronounced decrease in the degree of conjunctival hyperemia than in example 9.

Example 11

Rabbit number 11. Placebo instillations (0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl) were performed in both eyes (OS and OD) 3 times a day for 30 μl.

The clinical manifestation of uveitis - eyelid edema - was assessed in conditional scores on a four-point scale: absence of a sign - 0, manifestations of a weak degree - 1, medium - 2, strong - 3.

3 day 4 day 5 day 8 day OD 3 3 3 2 OS 2 2 3 2

Placebo instillations in both eyes in rabbit No. 11 did not lead to a decrease in eyelid edema. Throughout the experiment, this clinical sign was pronounced.

Example 12

Rabbit number 2. Superoxide dismutase was instilled at a concentration of 500 kU / ml in a 0.15 M NaCl solution, pH 7.5, in both eyes (OS and OD) 3 times a day for 30 μl.

The degree of edema of the eyelids was determined as in example 11.

3 day 4 day 5 day 8 day OD 2 one 0 0 OS 2 one 0 0

Instillations of superoxide dismutase solution in both eyes of rabbit No. 2 led to a decrease in eyelid edema, which disappeared by the 5th day.

Example 13

Rabbit number 8. An instillation of a solution of the claimed pharmaceutical composition at a concentration of 10 mg / ml (500 cU / ml) in water, pH 7.5, was carried out in both eyes 3 times a day for 30 μl.

The degree of edema of the eyelids was determined as in example 11.

3 day 4 day 5 day 8 day OD one 0 0 0 OS one one 0 0

Instillations of the claimed pharmaceutical composition in both eyes of rabbit No. 8 led to a more pronounced and earlier reduction of edema of the eyelids than in example 12.

Example 14

Rabbit number 9. Placebo instillations (0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl) were performed in both eyes (OS and OD) 3 times a day for 30 μl. The clinical manifestation of uveitis — fibrinous deposits — was assessed in conditional scores on a four-point scale: absence of a sign — 0, manifestations of a weak degree — 1, medium — 2, and strong — 3.

2 day 4 day 7 day 9 day 11 day 14 day 16 day 21 day OD 2 2 3 2 2 3 2 2 OS 2 3 2 2 2 2 3 2

Placebo instillation in both eyes of rabbit No. 9 did not lead to a decrease in the number of fibrinous deposits. Throughout the experiment, fibrin was detected in large amounts in the moisture of the anterior chamber.

Example 15

Rabbit number 4. Superoxide dismutase was instilled at a concentration of 250 kU / ml in a 0.15 M NaCl solution, pH 7.5, in both eyes (OS and OD) 3 times a day for 30 μl.

The degree of fibrinous deposits was determined as in Example 14.

2 day 4 day 7 day 9 day 11 day 14 day 16 day 21 day OD one 2 one 2 one one one one OS 2 2 one one one 2 2 one

Instillation of a superoxide dismutase solution in both eyes of the instillation rabbit No. 4 resulted in a decrease in fibrinous deposits than in a rabbit receiving a placebo (Example 14).

Example 16

Rabbit number 6. An instillation of a solution of the claimed pharmaceutical composition at a concentration of 5 mg / ml (250 kU / ml) in 0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl and 1 mg / ml benzalkonium chloride, in both eyes was performed 3 times 30 μl per day.

The degree of fibrinous deposits was determined as in Example 14.

2 day 4 day 7 day 9 day 11 day 14 day 16 day 21 day OD one one one one one one one one OS one one one one one one one one

Instillations of the claimed pharmaceutical composition in both eyes of rabbit No. 6 led to the fact that inflammatory manifestations in the internal structures of the eye — fibrinous deposits — were less pronounced than in a rabbit receiving superoxide dismutase (Example No. 15).

A study of the effect of superoxide dismutase and the claimed pharmaceutical composition on antioxidant activity in the lacrimal fluid of rabbits with an alkaline burn of the cornea.

Modeling a burn of the central part of the cornea.

When modeling the size and depth of the alkaline burn of the cornea, d = 7 mm circles made of thin cotton fabric were used, saturated with 10% NaOH solution, which was applied to the central region of the cornea for 40 seconds, then the eyes were washed with physiological saline in 20 ml portions. For pain relief, a 2.5% chlorpromazine solution was used in combination with a 0.5% seduxen solution (1: 1), which was administered subcutaneously (0.5 ml / kg body weight). At the same time, local anesthesia was performed by instillation of a 0.5% dicaine solution on the cornea.

Tear fluid was taken from animals before and on certain days after a burn with the help of circles of filter paper, which were placed in the lower arch of the conjunctival sac for 5 min. The tear components were eluted with physiological saline (1 circle - 50 μl). The eluate was centrifuged and the supernatant was used for research.

The antioxidant activity in the tear was determined by the chemiluminescent method in the model system hemoglobin - hydrogen peroxide - luminol, in which luminol acts as an oxidation substrate. The value of antioxidant activity was expressed in trolox equivalents, for which purpose a calibration curve was constructed for the dependence of the latent period of chemiluminescence on the concentration of trolox according to [Vladimirov Yu.A. Free radicals and antioxidants. (1998) News. RAMP, No. 7, 43-51]. Statistical processing of the results was performed using the Mann-Whitney U-test.

Example 17

Rabbit No. 16 received placebo instillation (0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl).

Rabbit No. 18 received instillations of a solution of superoxide dismutase at a concentration of 50 kED / ml in a 0.15 M NaCl solution, pH 7.5.

Rabbit No. 17 received instillations of the claimed pharmaceutical composition at a concentration of 50 kU / ml in 0.05 M phosphate buffer, pH 7.5, containing 0.15 M NaCl and 1 mg / ml benzalkonium chloride.

The results are shown in figure 1.

After a corneal burn in the period of 7-14 days, the antioxidant activity determined in the tear fluid significantly decreases. In a rabbit treated with superoxide dismutase, antioxidant activity not only did not decrease, but even significantly exceeded the norm. The level of antioxidant activity of tears in the treatment of the claimed pharmaceutical composition was higher than in the treatment with superoxide dismutase.

Thus, the above examples indicate that the introduction of superoxide dismutase into nanoparticles and local application of the claimed pharmaceutical composition enhances and prolongs the positive effect of the enzyme on the course of the inflammatory process in the eye, as well as more effectively reduces the number of free radicals during inflammation.

Given that the physiological characteristics of the eye of a rabbit and a human are identical, this pharmaceutical composition can be recommended for use in both veterinary medicine and in the clinic.

Claims (6)

1. A pharmaceutical composition for topical application in inflammatory eye diseases, characterized in that it is a solution of the active substance in the form of superoxide dismutase incorporated into nanoparticles based on a crosslinked methoxy-poly (ethylene glycol) -poly (L-lysine) block copolymer, and target additives, while the content of superoxide dismutase is 50-500 cED / ml. 2. The composition according to claim 1, characterized in that it is made in the form of eye drops or spray. 3. The composition according to claim 1, characterized in that as the target additives use either a buffering agent and / or 0.15 M sodium chloride. 4. The composition according to claim 1, characterized in that it contains a preservative. 5. The composition according to claim 1, characterized in that it further comprises preparations selected from the groups: either antibiotics, or steroids, or adrenergic blocking agents, or vitamins, or macro- and microelements. 6. A method of treating inflammatory eye diseases, which consists in installing into the conjunctival cavity of the eye a pharmaceutical composition according to claims 1-5, containing an effective amount of superoxide dismutase in a dose of 1.5 to 15 cED daily 2-3 times a day, lasting from 1 week to moment of completion of the inflammatory process.

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