EA008737B1 - Preparation for the treatment and prophylaxis of conjunctivitis and keratitis of different etiology (variants), method for use thereof - Google Patents

Abstract

The invention relates to a pharmacy medicine and can be used in medical practice as a monotherapy and in a multipurpose treatment of conjunctivitis and keratitis of different etiology.Medical preparations are proposed synthesized on the base of chemical interaction of disulfide-containing peptides and nitrogen base and/or nucleosides of purine od pyrimidine base. A medical preparation is synthesized based thereon including also other disulfide-containing peptides and pharmacologically acceptable diluents.The above preparation (variants) has cytoprotective action, and us also capable to induce apoptosis of virus infected cells and to enhance stability of unaffected cells to infection by bacteria, viruses and other agents.The inventive preparation (variants) for the treatment and prophylaxis of conjunctivitis and keratitis of different etiology is produced as eye drops and comprises the following components:organic salt of adenine and disulfideglutathione, lithium salt of lipoic acid, dimethylsulfoxide and water for injections, ororganic salt of cytosine and disulfideglutathione, cystine, dimethylsulfoxide and water for injections, ororganic salt of inosine and disulfideglutathione, cystine, dimethylsulfoxide and water for injections, ororganic salt of adenosine and disulfideglutathione, lithium salt of lipoic acid, dimethylsulfoxide and water for injections.A method is proposed for the treatment of conjunctivitis and keratitis of different etiology.

Description

The invention relates to the pharmaceutical industry and can be used in medical practice in monotherapy mode and in the complex treatment of conjunctivitis and keratitis of various etiologies.

One of the alarming moments of modern ophthalmology is a sharp increase in the role of contact lenses in the occurrence of ulcerative lesions of the cornea. It is believed that in the United States from 27 to 33% of all bacterial keratitis is associated with the wearing of contact lenses [1]. According to 8. RPIDGs16sg. the likelihood of the risk of bacterial keratitis when wearing contact lenses is 0.21% per year. increasing 10-15 times in those. who leaves the lenses for the night [2]. According to other sources. out of 1500 patients. wearing contact lenses. corneal ulcer occurred in 0.8% [3]. According to our observations. almost all sick. admitted with severe corneal ulcer. caused by a pyocyanic stick. used contact lenses. violating instructions for carrying or storing them. Prolonged wearing of contact lenses (more than 24 hours) leads to an increase in the desquamation of the corneal epithelium. and the resulting epitheliopathy (microerosion) contributes to the adhesion of the pyocyanic stick. It is shown. that the worse the transport of oxygen through the lens. the stronger is the desquamation of the epithelium and the greater is the likelihood of adhesion of the pseudomonas aeruginosa [4]. The ratio of causative agents of ulcerative lesions is expressed most reliably by the following figures: staphylococcus - 45%. Streptococcus - 12%. blue pus bacillus - 10%. mushrooms - 7%. acantameba - 1.6%. and for corneal ulcers in children: staphylococcus - 43.7%. Streptococcus - 18.8%. Pseudomonas aeruginosa - 9.4%. mushrooms - 17.2%. acantameba - 1.6% [5].

In general, there has recently been a shift towards an increase in the proportion of gram-negative pathogens: alike. according to research. held in the USA. the ratio of gram-positive and gram-negative pathogens of bacterial keratitis from 81.8% / 18.2% in 1993 changed to 51.4% / 48.6% in 1997 [6].

Another feature of bacterial corneal ulcers is a large number of strains of pathogens. antibiotic resistant aminoglycoside groups: so. according to literary data. 63.6% of pathogens were resistant to gentamicin [7]. Of particular concern are the reports of the growing resistance to the new antibiotics of the quinolone group. According to research in the United States. the number of strains of staphylococcus. resistant to ciprofloxacin. increased from 5.8 in 1993 to 35% in 1997 and the number of staphylococcal strains to ofloxacin, respectively, from 4.7 to 35% [6]. In India, 22 strains of Pseudomonas purulent were isolated. resistant to ciprofloxacin [7]. It is considered. that the widespread use of ciprofloxacin in general medical practice led to a jump in the number of resistant pathogens to 76-82% [6].

It is shown. that wearing contact lenses is a risk factor for fungal keratitis; but particular attention should be given to the information. that lenses are associated with up to 85-86% of acantamebic keratitis [8. 9]. Slow development of akantamebny keratitis. poor diagnostic options and difficulties with chemotherapy lead to. that they are usually recognized in advanced cases or after keratoplasty [10]. In practical terms, noteworthy research. identified secondary bacterial infection with acanthamebic keratitis from 10 [9] to 58% of patients [11]. This allowed suggest. that the secondary microflora plays a pathogenetic role in the development of acanthamestic keratitis. i.e. bacteria serve as a source of food for amoebas until then. until necrosis of the stroma makes corneal degradation products available for food [12]. A serious and frequent consequence of adenoviral conjunctivitis is dry eye syndrome (CVD). If in 1995 we assumed. which is about 20% of patients. after adenovirus infection of the eye. VCC develops [13]. then the latest research. performed together with E.V. Yani have shown. that a tearing disorder is detected in a mild degree in 21% and in a severe degree in 22% of patients.

The treatment of infectious eye diseases is very difficult and must always be complex. including agents as specific (antibacterial. antiviral. anti-fungal. anti-parasitic). and pathogenetic (anti-inflammatory and antiallergic. metabolic and immunological effects) therapy.

Known means. used in recent years in the practice for the treatment of keratitis and conjunctivitis of various etiologies [14-16].

Antibacterial agents

Eye drops and eye ointment with 0.3% tobramycin (Tobrex) are widely used in ophthalmic practice. For ulcers of the cornea of moderate severity. usually caused by staphylococcus or streptococcus. Tobrex eye drops are used 6-8 times. and eye ointment - 3-4 times a day. To prevent infection in surgical interventions on the cornea, Tobrex's effectiveness was convincingly demonstrated by the example of eye drop installations after excimer laser refractive keratoectomy.

Okacin eye drops contain 0.3% lomefloxacin. broad-spectrum antibiotic from the quinolone group. Drops have a pronounced therapeutic effect in the treatment of severe corneal ulcers. including those caused by Pseudomonas aeruginosa and gonococcus (instillation 6-8 times per day). in the treatment of staphylococcal. streptococcal and other bacterial corneal ulcers (instillation 6 times a day). in the treatment of bacterial conjunctivitis and blepharitis. in the prevention of injury infection

- 1 008737 cornea and corneal surgery. Okacin eye drops are also effective in the treatment of chlamydial conjunctivitis.

In cases of severe ulcerative lesions of the cornea, an urgent choice of antibiotic therapy is necessary, since the active course of the disease can lead to perforation of the cornea within 1-2 days. It should be borne in mind that monotherapy with ciprofloxacin guarantees up to 70% positive results [6], and used in the United States since 1978 as a standard method of combining gentamicin and cefazolin - a maximum of 96% [17]. Apparently, today complex therapy should be considered the most promising, including two antibiotics - Okacin and Tobrex.

Vitabact - 0.05% pikloksidina - antiseptic with a broad antibacterial spectrum of action. Vitabact is effective against many types of bacteria that cause such widespread eye diseases as conjunctivitis, chronic and subacute, blepharoconjunctivitis, blepharitis.

Kolbiotsin - the antibacterial drug which is issued in the form of eye drops and ointment. Kolbiotsin includes 3 antibiotics: chloramphenicol, colistin, romethetracycline. The drug is active against gram-positive and gram-negative bacteria, spirochaetes, chlamydia, mycoplasmas, rickettsia and other pathogens [18].

Combination products, including antibiotic and corticosteroid

Garazon - eye drops, including gentamicin (0.3%) and betamethasone (0.1%). Drops have a double action - a broad antibacterial and powerful anti-inflammatory. Most often, Garazon is used for postoperative management.

Tobradex - eye drops, including tobramycin (0.3%) and dexamethasone (0.1%). The drug is used in inflammatory eye diseases, when a complex effect is necessary, to prevent infection and anti-inflammatory action after surgery on the conjunctiva and the eyeball.

Eubetal - eye drops and ointment containing 3 antibiotics (chloramphenicol, colistin, romethetracycline) and betamethasone.

Antiviral drugs

Valacyclovir (Valtrex) is an acyclovir b-valyl ester. Valaciclovir, as well as acyclovir, is active against the herpes virus, but exceeds the latter by 4-5 times in bioavailability [19].

Lokferon is a human leukocyte α-interferon with an activity of 10,000 IU in a vial, developed and produced by Biomed them. I.I. Mechnikov [20]. Lockferon eye drops are well tolerated, have a therapeutic effect in the treatment of herpetic keratitis, reducing the duration of treatment by an average of 4 days compared to IMU drops, and in treating epidemic keratoconjunctivitis, reducing the duration of treatment by an average of 4.3 days compared to native interferon.

Immunomodulatory agents

Affinoleukin is a drug containing transfer factor proteins isolated from human leukocytes. Subcutaneous injections of Affinoleukin in the treatment of herpetic keratitis can reduce the treatment time by an average of 5-7 days [21].

Cyclolip is a domestic liposomal eye drop containing 2% cyclosporine, a powerful selective immunosuppressive drug. Cyclolip has a pronounced therapeutic effect in keratoplasty and in the treatment of inflammatory eye diseases with a proven or suspected immunological mechanism of development: uveitis, keratouveiitis, keratitis, hypopionuveitis with Behcet's disease, scleritis, dry eye syndrome [22].

Ophthalmoferon - 1 ml of eye drops contains a recombinant human interferon alpha-2b not less than 10,000 IU, an antihistamine preparation - diphenhydramine - 0.001 g, an artificial tear.

Antiallergic and anti-inflammatory drugs

Allergodil - eye drops containing 0.05% of acelastine hydrochloride. The drug is a blocker of histamine ^ receptors. In addition, inhibits the release of inflammatory mediators from mast cells.

Spersallerg eye drops contain antazolin, which has an antihistamine effect, and tetrizolin - a vasoconstrictor. This combination provides the most rapid and pronounced effect.

Alomid - eye drops containing 0.1% lodoxamide tromethamine. The droplets stabilize the mast cell membranes, prevent the antigen induced release of histamine and other allergy mediators. At the same time, Alomid inhibits the migration of eosinophils and the release of enzymes and cytotoxic factors from them. Alomid eye drops have proven effective in the complex treatment of dry eye syndrome, adenoviral conjunctivitis, chlamydial conjunctivitis.

Maxidex, eye drops and eye ointment containing dexamethasone (0.1%). Compared with other drops of dexamethasone, Maxidex favorably differs in its polymer base, which creates a fine suspension, which, on the one hand, provides a prolonged effect of dexamethasone and, on the other hand, better tolerability of the drug.

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Prenacid - eye drops and eye ointment containing desonide disodium phosphate.

Naklof - eye drops containing diclofenac sodium. Like other nonsteroidal anti-inflammatory drugs, Naklof inhibits prostaglandin synthesis.

These drugs, with rare exceptions (Affinoleukin, Ophthalmoferon), contain broad-spectrum antibacterial drugs, or steroid group drugs and therefore are powerful immunosuppressants. This means that the system of local immunity, being initially a weak point in infectious-inflammatory diseases, is increasingly destroyed in the course of treatment. Remissions are becoming less frequent, susceptibility to infection is increasing, and the process becomes chronic with the development of metabolic disorders in the cells. At a certain stage, destructive processes become prevalent, determining the nature and severity of the chronic infectious-inflammatory process.

Individual substances are known that are obtained on the basis of the chemical interaction of disulfide-containing peptides with nitrogenous bases and / or purine or pyrimidine nucleosides of nature [23]. These organic salts have unique biologo-pharmacological effects, the integrative results of which are the ability to control the ratio of humoral and cellular immunity, as well as the metabolic processes underlying cell proliferation, differentiation and apoptosis.

The task of the claimed invention is the creation of tools for the prevention and treatment of conjunctivitis and keratitis of various etiologies, with both antibacterial and antiviral activity, immunocorrective action with activation of the local immunity system, including resistant macrophages of the eye tissues.

The technical result of the claimed invention is the development of a means in the form of eye drops, possessing a cytoprotective effect (capable of restoring cell metabolism), as well as capable of inducing apoptosis of virus-infected cells and increasing the resistance of unaffected cells to infection by bacteria, viruses and other agents, as well as developing a method of using this tool . The problems of treating conjunctivitis and keratitis of various etiologies have been resolved through the use of agents with cytoprotective and immunocorrective effects, as well as anti-inflammatory and metabolic therapies.

The technical result is achieved due to the use in the composition of the substance substances obtained on the basis of the interaction of disulfide-containing peptides and nitrogenous bases and / or nucleosides of purine or pyrimidine nature, other disulfide-containing peptides and pharmacologically acceptable solvents.

As the preferred embodiment of the claimed invention, providing a new level of solution to the problem of local infectious-inflammatory diseases, keratitis and conjunctivitis, pharmaceutical compositions are proposed that include organic salts of bis- (y-L-glutamyl) -L-cystinyl-bis-glycinate sodium ( disulfide glutathione) with nitrogenous bases: 6-aminopurine (adenine) and / or 2-oxo-4-aminopyrimidine (cytosine);

organic disulfide glutathione salts with nucleosides: 9-3-0-ribofuranosylhypoxanthine (inosine) and / or 9-3-O-ribofuranosyladenine (adenosine);

bis- [6,8-dithio-octane] (lipoic acid) and / or cystine;

dimethyl sulfoxide (DMSO) as a pharmaceutically acceptable carrier of the preceding ingredients.

The essence of the invention lies in the fact that a tool (variants) was developed for the prevention and treatment of conjunctivitis and keratitis of various etiology in the form of eye drops, which include, wt.% Organic adenine salt and disulfide glutathione, lithium lipoic acid salt, dimethyl sulfoxide and water for injection with the following ratio:

the organic salt adenine ai disulfide glutathione 1.0-3.0 lithium lipoic acid salt 0.1-0.3 dimethyl sulfoxide 0.05-0.5 water for injections, the rest organic salt of cytosine and disulfide glutathione, cystine, dimethyl sulfoxide and water for injection at the following ratio:

organic salt of cytosine and disulfide glutathione 1.0-3.0 cystine 1.0-3.0 dimethyl sulfoxide 0.05-0.5 water for injection, the rest organic salt of inosine and disulfide glutathione, cystine, dimethyl sulfoxide and water for injection with the following ratio:

organic salt of inosine and disulfide glutathione 1.0-3.0 cystine 1.0-3.0 dimethyl sulfoxide 0.05-0.5 water for injection, the rest organic salt of adenosine and disulfide glutathione, lithium salt of lipoic acid, dimethyl sulfoxide and water for injection with the following their ratio:

organic salt of adenosine and disulfide glutathione 1.0-3.0 lithium lipoic acid 0.1-0.3 dimethyl sulfoxide 0.05-0.5 water for injection the rest

A method for the prevention and treatment of conjunctivitis and keratitis of various etiologies has been developed, according to which the indicated remedy (variants) is used as instillations 3 times a day, as the inflammatory process is relieved, the number of instillations is reduced to 2 times a day, the treatment is carried out during the time required to achieve a therapeutic effect.

It should be noted that so far the proposed pharmaceutical compositions have not been used in clinical practice for the treatment of conjunctivitis and keratitis of various etiologies.

In the case of obtaining organic disulfide glutathione salts with nitrogenous bases and / or purine or pyrimidine nucleosides of nature, the ionized carboxyl group of the glycine residue of the disulfide glutathione molecule acts as an anionic salt, and the protonated nitrogen atom inside the heterocycle of the nitrogenous base (which is the reason for which the core group is used). or nucleosides (for example, inosine or adenosine) with protonated nitrogen atom N1.

The method of obtaining the organic salt of 6-aminopurine (adenine) and / or 2-oxo-4-aminopyrimidine (cytosine) and bis- (y-E-glutamyl) -b-cystinyl-bis-glycine (disulfide glutathione), in which the disulfide glutathione molecule acts, and the adenine and / or cytosine molecule acts as a cation. The equivalent amount of powdered adenine and / or cytosine is added to the solution of the disulfide glutathione salt while mixing (45 ° С) substances), by le which the solution was filtered and the isolated end product by lyophilization.

The method of obtaining organic salt of inosine (9-3-0-ribofuranosyl-hypoxanthine) and / or adenosine (9-3-E-ribofuranosyladenine) and disulfide glutathione (bis- (y-E-glutamyl) -b-cistinyl-bisglycine), which as anion is a disulfide glutathione molecule, and as a cation molecule of inosine and / or adenosine, is that an equivalent amount of powdered inosine and / or adenosine is added to the solution of the dilithium salt of disulfide glutathione, with stirring and at a temperature of 45 ° C dissolving substances (substances), after which the solution is filtered and produce the final product using lyophilization.

Examples of specific embodiments of the invention.

Example 1 (formulation 1).

Organic salt of 6-aminopurine (adenine) and bis- (y-l-glutamyl) -b-cystinyl-bis-glycinate lithium (lithium disulfide glutathione) 20.0 g Bis- [6,8-dithiooctanate cast] (lithium lipoic acid) 2.0 g Dimethyl sulfoxide (DMSO) 1.0 g Water for injections up to 1 l.

Prepare the calculated amount of a 0.1% solution of DMSO in water for injection and heat it to a temperature of 45 ° C. At the same temperature, the lithium salt of lipoic acid and the organic salt of adenine and lithium salt of disulfide glutathione are dissolved in the resulting solution. The resulting solution is subjected to sterile filtration and poured into vials. Bottles hermetically sealed.

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Example 2 (formulation 2).

Organic salt of 2-oxo-4-aminopyrimidine (cytosine) and bis- (y-l-glutamyl) -b-cystinylbis-glycinate lithium (lithium salt of disulfide glutathione) 20.0 g Cystine 20.0 g Dimethyl sulfoxide (DMSO.) 1.0 g Water for injections up to 1l.

Prepare the calculated amount of a 0.1% solution of DMSO in water for injection and heat it to a temperature of 45 ° C. In the resulting solution, cystine and the organic salt of cytosine and the lithium salt of disulfide glutathione are successively dissolved at the indicated temperature. Next, proceed as described in example 1 (recipe 1).

Example 3 (recipe 3).

Organic salt of 9-p-O-ri.bofuranosylhypoxanthin (inosine) and bis- (y-glutamyl) b-cystinyl-bis-glycinate lithium (lithium salt glutathione disulfide) 20.0 g Cystine 20.0 g Dimethyl sulfoxide (DMSO) 1.0 g Water for injections up to 1 l.

Prepare the calculated amount of a 0.1% solution of DMSO in water for injection and heat it to a temperature of 45 ° C. In the resulting solution, cystine and the organic salt of inosine and the lithium salt of disulfide glutathione are successively dissolved at the indicated temperature. Next, proceed as described in example 1 (recipe 1).

Example 4 (recipe 4).

Organic salt of 9-P-O-ribofuranosyladenine (adenosine) and bis- (y-g-glutamyl) b-cystinyl-bis-glycinate lithium (lithium disulfide glutathione salt) 20.0 g Bis- [6,8-dithiooctanate lithium] (lithium lipoic acid salt) 2.0 g Dimethyl sulfoxide (DMSO) 1.0 g Water for injections up to 1 l.

Prepare the calculated amount of a 0.1% solution of DMSO in water for injection and heat it to a temperature of 45 ° C. In the resulting solution, at the same temperature, the lithium salt of lipoic acid and the organic salt of adenosine and the lithium salt of disulfide glutathione are dissolved. Next, proceed as described in example 1 (recipe 1).

As a result of preclinical studies, it has been established that the proposed remedy (variants) has unique biological and pharmacological effects, providing an immunomodulatory effect, including activation of anti-infective immunity, normalization of metabolic processes in the cells of eye tissues, therefore, activation of reparative processes, i.e. epithelialization of sites damage, along with the development of anti-inflammatory cytokines.

At the same time, disulfide-containing peptides (lipoic acid, cystine) regulate the thiol-disulfide exchange of cells, which is the basis of their bioenergy, therefore, determine the resistance to damaging factors.

Organic salts of disulfide glutathione with nitrogenous bases and / or nucleosides, along with pronounced metabolic effects, regulate endogenous production of cytokines, including interferon (IFN) alpha and gamma, which determines their immunorehabilitation and antiviral effects.

In addition, these compounds correct the ratio of cytokine production of TM / T2 class with the predominant activation of T111 cells due to stimulation of endogenous production of IL-12, which ensures a stable level of cell-mediated immune response, including the functional capacity of resident macrophages.

Dimethyl sulfoxide, being a unique transporter of ingredients, provides the functions of a pharmaceutically acceptable carrier, and also has a bactericidal effect.

The results of preclinical studies of general toxicity made it possible to attribute the claimed agents to practically non-toxic medicinal substances - class 5 [24, 25].

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In microbiological experiments with Staphylococcus aureus culture, a sufficiently high bacteriostatic activity of pharmaceutical compositions 1 and 2 was established with respect to the strains of this microorganism, which made it possible to conduct studies to evaluate the therapeutic efficacy of the drug on a model of viral-bacterial conjunctivitis caused in animals of Z. aigeic in combination with enteroviruses . Thus, according to the ophthalmological, including biomicroscopy, histomorphological and microbiological studies of the specific activity of pharmaceutical compositions 1 and 2, it was found that the effectiveness of the drugs is not inferior, and in terms of eliminating conjunctival edema, it is superior to the drugs of the traditional treatment of this eye disease. In the treatment of pharmaceutical compositions 1 and 2 in any case there was no residual effects of conjunctivitis, especially complications in the form of damage to the corneal epithelium. The treatment with pharmaceutical compositions 1 and 2 in combination with traditional therapy drops (levomycetin, interferon) has been very successful. Therapy of viral-bacterial conjunctivitis in all cases led to the elimination of the bacterial flora - at the end of the experiment, the growth of colonies Z. igeik was not observed in any of the treated animals. In addition, new drops have a broad spectrum of antibacterial activity.

All variants of the drug, taking into account their differentiated use in various nosological forms of eye diseases in the context of clinical studies, demonstrated a high therapeutic effect due to the immunomodulating activity of drugs due to the activation of local immunity, along with adjustable stimulation of the function of resident macrophages; cytoprotective activity of drugs due to the activation of metabolism and bioenergetics of eye tissue cells;

antibacterial and antiviral activity of drugs due to immunocorrective effects, including by stimulating the production of endogenous interferons;

anti-inflammatory and reparative effects of drugs due to the regulation of the content of pro-inflammatory cytokines and products of free radical oxidation, due to the regulation of the lipid peroxidation system - antioxidant protection (POL-AOD system);

induction by drugs of apoptosis of infected cells, which ensures the potentiation of the effects of traditional antibacterial and antiviral chemotherapy;

desensitizing effect of drugs due to the regulation of the immunological and biochemical phases of the allergic reaction in the tissues of the eye.

The method of use for the treatment of conjunctivitis and keratitis of various etiologies

The proposed tool (options) used in the form of eye drops for the prevention and treatment of the following nosological forms:

adenoviral and herpetic eye disease;

acute bacterial conjunctivitis;

allergic conjunctivitis;

dry keratoconjunctivitis with severe corneal lesions;

corneal ulcers;

anterior uveitis, corneal dystrophy, especially with bullous phenomena and severe corneal edema;

infectious keratouveitis (viral, bacterial, fungal) with pronounced metabolic lesions of the cornea;

allergic (autoimmune) keratitis and keratouveitis with metabolic lesions of the cornea;

dry eye syndrome;

postoperative rehabilitation; post-traumatic rehabilitation; conditions after photorefractive keratoectomy.

According to the invention for the treatment of adenoviral and herpetic lesions of the eyes, it is preferable to use an agent in accordance with examples 2 and 3 (formulations 2 and 3).

According to the invention for the treatment of conjunctivitis and keratitis of bacterial etiology, preferably using the tool in accordance with examples 1 and 4 (formulations 1 and 4).

According to the invention, for the treatment of keratitis and keratouveitis with metabolic lesions of the cornea, corneal dystrophies, especially with bullous phenomena and severe corneal edema, the condition after photorefractive keratoectomy, dry eye syndrome, dry keratoconjunctivitis with marked corneal lesion is preferable to use an agent in accordance with example 1 ).

According to the invention for carrying out postoperative and post-traumatic rehabilitation it is preferable to use an agent in accordance with Example 3 (formulation 3).

According to the invention for severe ulcers of the cornea, preferably using the agent in accordance with example 4 (formulation 4) in the acute period and the agent in accordance with example 1 (prescription

- 6 008737 pa 1) in the period of convalescence.

According to the invention, a method of treating conjunctivitis and keratitis of various etiologies is to assign the proposed pharmaceutical compositions to a patient in need, and they are used at least three times a day during the period necessary to achieve a therapeutic effect.

According to the invention, the proposed remedy (variants) is used in the form of instillations 3 times a day, as the inflammatory process is relieved, the number of instillations is reduced to 2 times a day, the treatment is continued until the symptoms of the disease disappear.

The following are examples of the specific use of the drug (variants) in the treatment of patients with conjunctivitis and keratitis of various etiologies.

Examples of the clinical application of the proposed means (options)

Example 5

Last name, first name of the patient:

G. Andrey Vladimirovich

Gender: male

Age: 32 years

Outpatient card No. 2198 Diagnosis: ΟΏ - Adenoviral keratoconjunctivitis.

Complaints during the inspection: On photophobia, tearing, reduced vision, feeling of a foreign body in the right eye, redness of the eyeball. Medical history of the disease: Got sick a week ago, when he noticed a feeling of a foreign body in the eye, then redness of the eyeball. The next morning, I noticed swelling of the upper and lower eyelids, more intense redness of the eyeball, and tearing. Appealed to the ophthalmologist at the place of residence. Therapy was prescribed, which did not lead to a positive effect, from the complaints joined the deterioration of vision in his right eye. Previous treatment: Eye drops: Oftan-IMU, 4 times a day, Leukocyte interferon, 7-8 times a day. Eye ointment: tetracycline, 2 times a day.

Objective inspection: Conjunctiva sharply hyperemic, mucosa in the form of “cobblestone pavement”, copious mucous discharge, pronounced tearing, small epithelial point opacities on the cornea stained with fluorescein. Visual acuity - OO - 0.6; 08 - 1.0.

The course of treatment with the tool in accordance with examples 2 and 3 (formulations 2 and 3): The tool in accordance with example 2 (formulation 2): buried 3 times a day, 5 drops in the right eye, 3 drops in the left eye for 5-7 days. The tool in accordance with example 3 (recipe 3): buried 2 times a day in the right and left eye for 5-7 days in monotherapy.

Conclusion

Conducting a course of therapy with this tool provided a positive trend, which was expressed in the absence of signs of inflammation of the right eyeball: the conjunctival mucosa is pale pink, smooth, foreign body feeling in the eye and tearing are absent, on the cornea there are 2 point opacities on the periphery of the cornea, unpainted with fluorescein, visual acuity - ΘΌ and 08 = 1.0.

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Example 6

Surname, name, patronymic of the patient: V. Galina Ardalionovna

Female gender

Age: 56 years

Case history No. 6006

Diagnosis: 08 - herpetic treelike keratitis. Complaints during the inspection: Decreased visual acuity of the left eye, pain in the eye, feeling of a foreign body in the eye, photophobia, tearing. Medical history of the disease: The first clinical manifestation of herpetic keratitis was about 3 years ago, exacerbations are observed about 6 times a year. This aggravation began on 28.11.2004, when she felt pain, tearing and photophobia in her left eye. She turned to the clinic of eye diseases of the State Medical Academy. I.I.Mechnikova. Objective inspection: The conjunctiva of the left eyeball is hyperemic; on the cornea, turbidity in the form of a tree branch, stained with fluorescein. Blur in the form of stains, undyed with fluorescein. The sensitivity of the cornea is absent. Visual acuity 08 - 0.2 (not corrected), Οϋ - 0.6 δρίι +2.0 diopters = 1.0. Prior therapy: Reaferon 500 thousand, subconjunctival, 7 days, mezaton 0.5 ml, subconjunctival, 7 days. A weak positive dynamics was obtained, which consists in reducing the cornea staining, a slight increase in sensitivity. To obtain a stable therapeutic effect, a course is prescribed using pharmaceutical compositions. The course of treatment with a tool in accordance with examples 1, 2 and 3 (recipes 1, 2 and 3): The tool in accordance with example 1 (recipe 1): they were buried 3 times a day in the left eye for 5 drops, in the right eye for 3 drops for 7 days, after which they switched to the product of example 2 (formulation 2). The tool in accordance with example 2 (recipe 2): instilled 5 drops in the left eye, 3 drops in the right eye 3 times a day for 7 days, after which they switched to remedy 3 (formulation 3), The tool in accordance with example 3 (recipe 3): buried in the left eye 5 drops 3 times a day for 14 days in monotherapy.

The patient's condition after the end of treatment:

Conjunctiva of the left eyeball is pale pink.

On a cornea the easy opacities which are not painted by fluorescein remain. The sensitivity of the cornea is restored.

Visual acuity 08 - 0.6 8rN + 2.0 diopters = 0.8; Οϋ - 0.6 8pH + 2.0 dptr = 1.0.

The level of cytokines in tears before and after treatment with an agent in accordance with examples 1-3 (recipes 1-3)

Duration of examination ILSHETA (pkg / ml) TNF alpha (pkg / ml) IFN alpha (pkg / ml) Norm 30.0 0.05 119.2 Before treatment 225 307 126.2 After treatment 41,8 4.3 205,8

Conclusion

Combination therapy with the use of tools in accordance with examples 1, 2 and 3 (recipes 1, 2 and 3):

lack of patient complaints;

epithelization of corneal damage;

restoration of corneal sensitivity;

significant improvement in visual acuity;

an increase in the level of IFN alpha in a tear;

reducing the level of pro-inflammatory cytokines IL-1 beta and TNF alpha in a tear.

Example 7

Last name, first name of the patient: Gender:

Age:

Diagnosis:

M. Alexander Nikolaevich male years

- corneal ulcer, iridocyclitis, hypopyon.

Complaints during the inspection:

Medical history of the disease:

Objective inspection:

Previous treatment:

The course of therapy means in accordance with examples 1 and 4 (recipes 1 and 4):

Decreased vision in the left eye, pain and foreign body sensation in the eye, tearing.

I got sick 3 weeks ago, when I suffered an injury to my left eye, I went to the doctor after 5 days, and a corneal ulcer was diagnosed. The patient was hospitalized in the eye department of the City Ophthalmological Hospital No. 7 where the treatment was prescribed (see below). This treatment reduced inflammation, however, it was not possible to achieve the healing of a corneal ulcer. It is recommended to add Glutoftal eye drops to therapy.

The conjunctiva of the left eyeball is hyperemic, in the center of the cornea is an ulcer measuring 2 to 3 ml in diameter, stained with fluorescein. The reaction of the pupil to light is reduced (the action of mezaton), the anterior chamber of normal size, there is no hypopyon The sensitivity of the cornea is increased. Visual acuity 08 - 0.06 (not corrected), Οϋ -1.0.

Locally: chloramphenicol 0.25% eye drops, 5 times a day, subconjunctival gentamicin 0.3% 0.5 ml, mezaton - 0.5 ml. Parenteral administration: v \ m gentamicin 80 mg No. 5, vitamins of groups B and C. After the end of this course of therapy, a therapeutic effect was obtained in the form of a decrease in the inflammatory component, however, the ulcer did not heal. In this regard, a course of therapy was prescribed using pharmaceutical compositions.

The tool in accordance with example 1 (formulation 1): buried in the left eye 3 times a day for 7 days.

The tool in accordance with example 4 (formulation 4): instilled 3 times a day for 14 days.

The tool in accordance with example 1 (recipe 1) - on the background of traditional therapy, the tool in accordance with example 4 (recipe 4) - in monotherapy.

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The patient's condition after the end of treatment: The conjunctiva of the left eyeball is pink.

On the cornea, blurred as a spot, unpainted with fluorescein. Corneal sensitivity is normal.

Visual acuity 08 - 0.4; ΟΌ - 1.0.

The reaction of the pupil to light is alive.

The anterior chamber is of normal depth, there is no hypopion.

Recommended to conduct resorptional therapy.

Example 8

Last name, first name of patient: Gender: Age:

Medical history:

Diagnosis:

N. Lyudmila Igorevna female years № 1043

ΟΏ - dry eye syndrome, filamentous keratitis.

Complaints during the inspection:

Medical history of the disease:

Previous treatment:

Objective inspection:

Reduced vision, feeling of dryness and foreign body in the eye.

There was a decrease in vision more than a month ago. I turned to an ophthalmologist, who was diagnosed (see above) and prescribed treatment (see below). After a month of therapy, epithelization of the cornea is not observed, the feeling of dryness has somewhat decreased.

8-1. TayGosh 2% (diluted in a 1: 1 ratio with a solution of polyglucin) 1 drop 3 times a day for 30 days.

8-1. Those ag 8 Naashgak eye drops, 1 drop 5-6 times a day - 21 days.

At the time of inspection of the conjunctiva of the right eyeball is somewhat hyperemic, filamentous de-epithelization of the cornea, stained with fluorescein, is noted. Visual acuity of the right eye - 0.5 (not corrected), the left eye - 1.0.

The tool in accordance with example 1 (formulation 1): buried 3 times a day in the right eye for 14 days in monotherapy.

Objective inspection:

The course of treatment with the tool in accordance with example 1 (formulation 1):

The patient's condition after the end of treatment:

~ 'At the time of examination of the conjunctiva of the right eyeball pale pink, there are tender filamentous corneal opacities that are not stained with fluorescein. Visual acuity of the right eye - 0.9 (not corrected), the left eye 1.0.

Information sources

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4. 1) AD 1.K.O. Sottipyu Euye nea1! Nd. 1995; 8: 2-3.

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7. ООМз !ET Μ.Ν., Ko ^ а1кк1 К.Р., Oogbop U.E. Oriy! 1999; 106 (7): 1313-1318.

8. 1 Tauazi M., P! Gogo11 T’.M., 1ez! Er EB. e! a1. Ory! 1994; 101: 371-388.

9. KaiGtap N.E., Vaggop V.A., MsOopaM M.V. Sotea С1шгс1ч11 Е1ушд-8! Опе. 1997

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10. Kissho1o ϋ.Υ., Zyagta 8., Kebbu M.K. c1 a1. Or1I11a1to1odu. 1998; 105 (2): 252-262.

11. RPIDGS1BSG 8. Sotea, ex! Eta1 b15ea5e5 appbn aggod led 1gayita. Bieo 8g Egaps1wso. 1996; 17

12. Eo \\\\\\\\\\ c1 a1. Sotea 2-pb Ιηΐ. SopGsG. Pg. 1996; 77.

13. Tepu A.S., LETr MA, MagdOnv, T.R. c1 a1. You are a kegabb. A.A.O. 8g Egaps1wso. 1995; nineteen.

14. Encyclopedia of drugs / Annual collection. M., LLC RLS-2003, 2003, issue 10.

15. Vidal. Drugs in Russia. / Handbook, ed. 8th, M., "Astrafarmservice", 2002.

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Claims (5)

1. A tool for the prevention and treatment of conjunctivitis and keratitis of various etiologies, characterized in that it consists of eye drops containing an organic salt of adenine and disulfide glutathione, lithium salt of lipoic acid, dimethyl sulfoxide and water for injection in the following ratio, wt.%: organic salt of adenine and disulfide glutathione 1.0-3.0 lithium salt of lipoic acid 0.1-0.3 dimethyl sulfoxide 0.05-0.5 water for injection else 2. Means for the prevention and treatment of conjunctivitis and keratitis of various etiologies, characterized in that it consists of eye drops containing an organic salt of cytosine and disulfide glutathione, cystine, dimethyl sulfoxide and water for injection in the following ratio, wt.%: organic salt of cytosine and disulfide glutathione 1.0-3.0 cystine 1.0-3.0 dimethyl sulfide oxide 0.05-0.5 water for injection 3. A tool for the prevention and treatment of conjunctivitis and keratitis of various etiologies, characterized in that it consists of eye drops containing an organic salt of inosine and disulfide glutathione, cystine, dimethyl sulfoxide and water for injection in the following ratio, wt.%: organic salt of inosine and disulfide glutathione 1.0-3.0 cystine 1.0-3.0 dimethyl sulfoxide 0.05-0.5 water for injection 4. Means for the prevention and treatment of conjunctivitis and keratitis of various etiologies, characterized in that it consists of eye drops containing an organic salt of adenosine and disulfide glutathione, lithium salt of lipoic acid, dimethyl sulfoxide and water for injection in the following ratio, wt.%: organic salt of adenosine and disulfide glutathione 1.0-3.0 lithium salt of lipoic acid 0.1-0.3 dimethyl sulfoxide 0.05-0.5 water for injection else 5. A method for the prevention and treatment of conjunctivitis and keratitis of various etiologies, characterized in that the medicines according to claims 1-4 are used as instillations 3 times a day, as the inflammatory process is stopped, the number of instillations is reduced to 2 times a day, treatment is carried out in the course of time necessary to achieve a therapeutic effect.