EA018202B1 - Ophthalmological gel and a method for the use thereof - Google Patents

Abstract

The invention relates to medicine, in particular, to ophthalmology and can be used as an artificial lacrimal fluid for the treatment of “dry eye” syndrome, traumatic injuries, trophic disorders and chemical burn of cohjunctiva, cornea and diseases associated with cornea operations. The inventive ophthalmological gel comprises 0.2-1.0% low-cross-linked polyacrylic acid and/or derivatives thereof, comprising a carbixylic group, preservatives, stabilizers, a medicinal substance selected from a reparant group 1-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxypyrimidine (xymedon), clean water and has a pH value within the range pH of lachrymal liquid. According to the invention said gel variant further comprises an aqueous solution of polyethyleneoxcides, NaOH in the amount sufficient to prepare gel with pH 6.0-7.9, containing as preservatives and stabilisers benzalkonium choride, edetate disodium and aminoglycoside antibiotic - gentamicin sulfate with the following component ratio, wt.%: low-cross-linked polyacrylic acid and/or derivatives thereof, comprising a carboxylic group 0.2-1.0; 10-30% aqueous solution of polyethyleneoxide - 2-10; xymedon - 1-10; benzalkonium chloride – 0.005-0.015; edetate disodium (trilon B) – 0.002-0.004; gentamicin sulfate – 0.02-0.03; clean water - up to 100. The inventive gel production method consists in adding an aqueous 10-30% polyethylenoxide solution into a dry powder of low-cross-linked polyacrylic acid associated with rapid agitation, polyethylenoxide being taken at least in a tenfold excess with respect to the mass of the powder, in adding, while agitating, clean water in a quantity equal to 70-90% the total mass of the gel, in adjusting a pH value to a value of 6.0-7.0 by means of a sodium hydroxide solution, in adding, while agitating, an alkali stabilizer, preservative and antibiotic solution, which is previously prepared in a separate reactor, by mixing the aqueous solutions of benzalkonium chloride, bisodium edetate and gentamicin sulphate, in subsequently adding a 10-20% sodium hydroxide solution, in adding xymedon at a mass concentration of 1-10%, in adjusting, for the second time, the pH value to a required value 10-20% by means of a sodium hydroxide solution and in sterilizing the thus produced gel.

Description

The invention relates to medicine, in particular to ophthalmology, and can be used to treat dry eye syndrome as an artificial lacrimal fluid, treat traumatic injuries, trophic disorders and chemical burns of the conjunctiva, cornea, skin, and also during and after various operations the cornea.

State of the art

Clinical practice indicates that the proportion of patients with dry eye syndrome (CVH) in the structure of primary access to an ophthalmologist is 30-45%. The most common causes of treatment are menopause syndrome, pathology associated with the effects of keratitis and corneal dystrophy, ophthalmic office and monitor syndromes, tear production changes due to the installation of β-adrenergic receptor blockers and Sjögren's syndrome. Also, one of the common causes of instability of the lacrimal film is surgical interventions for refractive errors. Excimer laser radiation during surgery on the cornea causes damage to its epithelium, which leads to a breakdown in the connection between the tear and the surface of the cornea. The use of eye drops with a vasoconstrictive effect is quite common, which with frequent and prolonged use causes dry eyes, not to mention other complications.

The need to eliminate adverse effects (malnutrition, clouding of the cornea, poor epithelialization of the incision, and as a result, decreased vision) makes us look for new tools that contribute to the rapid regeneration of the tissues of the cornea of the eye.

Topical preparations are known - artificial tears, which are widely used to protect the cornea with reduced secretion of lacrimal fluid, with dry eye syndrome, to accelerate epithelialization of the cornea during injuries (including thermal burns of the conjunctiva and cornea), erosion and trophic ulcers of the cornea. These drugs are quite effective after plastic surgery on the eyelids, after keratoplasty, keratectomy, with eye irritation caused by smoke, dust, cold, wind, sun, salt water, contact lenses; after removal of toxic substances and foreign bodies from the eye; during gonioscopy, electroretinography, electrooculography, eye ultrasound, etc.

Local rehydratants are used in ophthalmology mainly in the form of eye drops (hypromellose, Lacrisin and others) and gels (carbomer 974P, Vidisik and others). The main requirements for tear substitutes are the physiological value of pH 7.2-7.4, optimal viscosity, transparency and colorlessness to maintain clear vision, as well as prolonged action.

The most famous gel is Vidisic Eye Gel (prospectus from фирмыγ. Mapp Rägta, Germany, 2005), intended to alleviate the symptoms of dry keratoconjunctivitis. It contains a rare cross-linked polyacrylic acid (Mm-4,000,000) 0.2%, sorbitol (4%), enhancing thixotropic properties, purified water (95.69%) and, as an auxiliary substance, which acts as a preservative and stabilizer, a cationic surfactant - cetrimide ( 0.01%). The hydrogel also contains sodium hydroxide in an amount sufficient to achieve a tear fluid pH of 7.2-7.8.

In the process of alkali neutralization of non-ionic polyacrylic acid units, the sodium salt of polyacrylic acid is formed, and sodium hydroxide molecules are adsorbed onto the polymeric units of polyacrylic acid, which determines both the swelling of the gel and its thixotropic properties, which are enhanced by sorbitol. Under the influence of shear forces (blinking), the gel passes into the liquid phase, contributing to its uniform distribution over the surface of the eyeball. At rest, the structure of the drug is restored. Polyacrylic acid and sorbitol, which are present even in that small amount, strongly bind water, thus, the drug remains on the surface of the eyeball for a long time. The refractive index of the gel (1.33651.3405) is very close to the refractive index of the cornea and tear film (1.375).

Vidisik gel is obtained by immersing a dry polymer on a water surface (wetting stage), after swelling and sedimentation of the polymer, the gel is mixed, auxiliary substances are introduced (stabilizer and preservative - citrimide, as well as a substance that regulates thixotropic properties - sorbitol).

In the treatment of more complex ophthalmic diseases that require the protective function of the cornea, stimulate the processes of regeneration of the cornea, as well as an anti-inflammatory effect, such as erosion of the cornea, eye burns, keratitis of various etiologies, dystrophic diseases of the cornea, as well as the prevention of corneal damage when wearing contact lenses, it is necessary to the composition of the gel to introduce a tissue regeneration stimulator.

Currently, the following helium preparations are used to enhance reparative regeneration: animal blood dialysates (Actovegin gel 20%, solcoseryl gel 20%), corneal protector of the cornea. The mechanism of action of most of these drugs is based on increased oxygen metabolism.

The active substance of Actovegin and Solcoseryl is a deproteinized hemoderivative from calf blood with low molecular weight peptides and nucleic acid derivatives. Drugs activate the metabolism in tissues, improve trophism and stimulate the regeneration process. Lack of data

- 1 018202 medicines are hypersensitivity to the drug, allergic reactions, local reactions: itching, burning, lacrimation, scleral injection.

The most famous gel selected by the authors for the prototype is Korneregel (prospectus of the company Ότ. Mapp Riatt, Germany, 2005).

Korneregel is a hydrogel based on the rare crosslinked polyacrylic acid of the carbomer (carbopol) brand, excipients - stabilizer and preservative - are cetrimide, disodium edetate is complex, and dexpanthenol (Panthenol) - (+) 2,4-dioxi is used as a medicinal substance -Y- (3-hydroxypropyl) -3,3-dimethylbutyramide, belonging to the group of reparants. Dexpanthenol contained in Korneregel turns into living cells into pantothenic acid, which does not perform an independent function, but is an integral part of coenzyme A (K ₀ A, K ₀ A-8H, widely distributed in living nature, almost key in many biosystems) ) and participates in many cellular reactions, as a result of which cell division is accelerated and epithelization takes place at an earlier date. In addition, the gels include sodium hydroxide, which is introduced to achieve the desired pH.

The method of preparation of Korneregel is similar to the method of preparation of Vidisik with the addition of a drug at the final stage.

The disadvantage of Korneregel gel is the relatively low viscosity of the gel, which requires frequent instillations. In some cases, due to insufficient viscosity, the preparations of this group did not form a stable lacrimal film, smoothing out irregularities of the cornea that arise after surgery.

The composition of Korneregel does not determine the thixotropic properties necessary for the treatment of a more complex complex of ophthalmic diseases. In addition, during the preparation of the gel, the main drug substance, dexpanthenol, is able to partially inactivate, due to the possibility of this compound being hydrolyzed both in an acidic medium when polyacrylic acid is added to the gel at the initial stage, and upon contact with sodium hydroxide in the process of bringing the gel to the required pH. Reactions occur by analogy with pantothenic acid hydrolysis reactions.

Pantothenic acid is a typical hydroxy acid in its properties, which can form derivatives both in the carboxyl group (amides) and in alcohol. Chemically, this acid and pantothenic alcohol are unstable in any medium (acidic and alkaline) - it is easily hydrolyzed to β-alanine and pantolactone.

Therefore, the pharmacological properties of panthenol and, accordingly, Korneregel will be determined by the method of preparation of the gel, preventing the hydrolysis of the medicinal substance, and the preservation of thixotropic and viscosity characteristics.

Disclosure of invention

The problem to which the invention is directed is to create an ophthalmic gel that provides the functions of a rehydration agent, keratoprotector and reparant, showing the necessary qualities of homogeneity, uniformity, viscosity, osmolarity, thixotropy on the surface of the eyeball.

This problem is solved by a group of inventions, united by a single inventive concept. The composition of the ophthalmic gel and the method of its preparation are proposed.

In the proposed ophthalmic gel containing 0.2-1.0% of a rare crosslinked polyacrylic acid and / or its derivatives containing a carboxyl group, preservatives, stabilizers, a medicinal substance from the reparant group, purified water, and having a pH value within the pH of the tear fluid, According to the invention, 1- (b-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-hydroxypyrimidine (xymedon) is used as a drug from the group of reparants.

Also according to the invention, the gel additionally contains an aqueous solution of polyethylene oxide, sodium hydroxide in an amount sufficient to obtain a gel with a pH of 6.0-7.9, contains benzalkonium chloride, disodium edetate and the aminoglycoside antibiotic gentamicin sulfate as preservatives and stabilizers in the following ratio of components , wt.%:

rarely cross-linked polyacrylic acid and / or its derivatives 0.2-1.0;

10-30% aqueous solution of polyethylene oxide 2-10;

Xymedon 1-10;

benzalkonium chloride 0.005-0.015;

disodium edetate (Trilon B) 0.002-0.004;

gentamicin sulfate 0.02-0.03;

purified water - up to 100.

The method of preparation of the proposed gel consists in the fact that with vigorous stirring in a dry powder of a rare crosslinked polyacrylic acid and / or its derivatives, an aqueous 1030% solution of polyethylene oxide taken in tenfold excess by weight relative to the powder is added, then 70-90% purified water from the total mass of the gel, after which the pH is adjusted to a value of 6.0-7.0 with sodium hydroxide solution, then added with stirring

- 2 018202 an alkaline stabilizer, preservative and antibiotic solution pre-prepared in a separate reactor by mixing aqueous solutions of benzalkonium chloride, edetate disodium and gentamicin sulfate, followed by the addition of 10-20% sodium hydroxide solution, after which xymedon is added in a mass concentration of 1-10% and the pH is again adjusted to the required value with a 1020% sodium hydroxide solution, the resulting gel is sterilized.

The essence of the proposed invention lies in the fact that as a medicinal substance from the group of reparants use xymedon {1- (b-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2oxypyrimidine} - a substance with anti-inflammatory and regenerative activity.

Polymers based on polyacrylic acid (PAA) and its derivatives (pH ~ 3) form complex compounds with amines (ethylenediamine, pyridine, morpholine, diethylamine, piperidine, etc.) (Polymers in Pharmacy, Chapter IV. Polymers and copolymers of acrylic and methacrylic acids, p. 65). Xymedon is an organic base (a derivative of the pyrimidine base), which, like other amines, forms complexes with terminal carboxyl groups of polyacrylic acid (a commonly used brand of Carbopol).

Since 56-68% of terminal carboxyl groups in the initial carbopols (pH ~ 3, dynamic viscosity 0.8 Pa-s), depending on the degree of neutralization of acid groups, complex compounds of amines with carboxyl groups of polymers either precipitate from an aqueous solution, or dissolve in it. Similarly, in neutral or slightly alkaline media, soluble complexes of polyacrylic acid with lysozyme, coumarin, insulin and other natural substances are formed.

Consequently, the formation of complex compounds of xymedon with carboxyl groups of carbopolis will depend on the sequence of input of sodium hydroxide, which regulates the degree of neutralization of carboxyl groups in the carbopol of 0.8 Pa-s. The necessary qualities of homogeneity, uniformity, viscosity, osmolarity, thixotropy of the proposed gel can be achieved only with a certain method of its preparation.

The most optimal pH for the introduction of Xymedon is pH ~ 6-7. The partial replacement of sodium ions with xymedon contributes not only to an increase in viscosity, but also to a decrease in osmolarity. The lower osmoticity (osmolarity) with respect to the corneal epithelium improves the quality of ophthalmic gels, since it is known that a hypotonic solution has a better effect on the corneal epithelium compared to isotonic (Agadopa R. et al. // Br. 1. Orya1., 2002, Hades; 86 (8), p. 879884). A slightly hypotonic solution counteracts the hyperosmolarity of the tear film, typical of dry eye syndrome, and restores normal osmotic pressure. The osmolarity of the polymer film with Xymedon 250-270 mOsm (for tears 303-310 mOsm).

The formation of PAA-Ximedon polymer-colloidal complexes leads to an increase in the viscosity of the medium without introducing an additional amount of sodium ions. In the table. Figure 1 shows examples of changes in viscosity with a carbopol solution at pH ~ 7 in the presence and absence of xymedon.

When dry carbopol is introduced into water, clumping occurs and a heterogeneous composition forms; the application of dry carbopol on the surface of the water leads to an increase in the process time, since mixing is unacceptable at this stage, especially in turbulent mode.

Preliminary wetting of the dry powder of crosslinked polyacrylic acid and its derivatives with a tenfold excess (by weight) of an aqueous 10-30% solution of polyethylene oxide with stirring with the further introduction of 70-90% purified water allows to reduce the preparation time of the helium base and to ensure high thixotropic properties and uniformity of the gel.

Phased adjustment of pH allows you to enter auxiliary components (stabilizers, preservatives, antibiotics), while maintaining the uniformity of the gel, without causing the formation of precipitation, flakes and turbidity.

It is proposed to use cationic surfactants as preservatives and stabilizers, for example benzalkonium chloride, complexon, for example disodium edetate (Trilon B), and an aminoglycoside antibiotic, for example gentamicin sulfate

- 3 018202

Gentamicin sulfate (Gent) ₂ -5Н ₂ 8О ₄

SG ^ ⁺ (CH ₃ ) ₂ CH ₂ C ₆ H ₅ ] Benzalkonium chloride

With the introduction of antibiotic salts and benzalkonium chloride simultaneously with disodium edetate (Trilon B) in a solution containing sodium hydroxide, the following processes can occur:

neutralization reactions with the formation of insoluble bases:

1) 2 [(Gent) 2-5Н2§О4] + 10 No. ОН 4 Gent + 5Ж8О4;

2) С1 | \ '(СНн.СН. Сб115 | + \ аОН ОН | \ (СН _; ).

the reaction of the formation of soluble complexes of Trilon B with bases: gentamicin and benzalkonium hydroxide (OH ^ CH3CS ^ SBVD):

noosn ₂ s _h sn ₂ soon _ζ Ν-ΟΗ-ΟΗ ^ Ν ₄ No. ОСН ₂ С СН ₂ СОО№ + 2 Gent

Ν & 2 EDTA (Trilon B)

Ghent НОСН ₂ С _{ч ζ} ΟΗ ₂ ΟΟΟΗ - Gent / I-СН-СН-Ν ^ No. ОСОН ₂ С СН ₂ СОО№ № ₂ EDTA (Gent) ₂

4) Νη ₂ EDTA + 2 OH '[H ⁺ (CH ₃ ) ₂ CH ₂ C _b H ₅ ] ->

[C ₆ H ₅ CH ₂ (CH _{3) 2} m1soo: _ζ οοο | ν (CH _{3) 2} CH ₂ C ₆ H ₅ ^{1 1} ΙΜ-ΟΗ ₂ · ΟΗ ₂ · Ν. ,, ^{] + n} 2 °

СН ₂ СОО№ СН ₂ СООЫа

As a result of the joint introduction of a mixture of gentamicin sulfate, benzalkonium chloride, trilon B in an alkaline solution, soluble complex compounds are formed that are uniformly distributed in the helium base.

Thus, only the joint introduction of an alkaline solution of stabilizers, preservatives and antibiotics into a helium base with a pH of 6.0-7.0 allows you to get a uniform, viscous gel, with sizes of tangles and globules less than 0.5 microns.

The introduction of xymedon in a neutral environment does not cause inactivation of the main drug substance. The introduction of xymedon into a slightly acidic medium leads to the formation of pink-crimson colored products of oxidative condensation (Reznik V.S., Muslinkin A.A., Shirshov A.N., Spiridonova N.A., Pashkurov N.G., Akamsin V.D. ., Gurylev EA, Chemical and technological fundamentals of xymedon production // Chemical and Pharmaceutical Journal, vol. 35, No. 12, 2001). At pH> 6, Xymedon is stable in gels. The introduction of xymedon at concentrations less than 1% does not lead to the necessary pharmacological action, does not cause an increase in viscosity and does not cause the necessary thixotropy. An increase in the concentration of xymedon above 10% does not improve the pharmacological effect and is not economically feasible. Secondary adjustment of the pH to the required value does not change the quality of the gels and does not cause xymedon inactivation.

Correction of pH with alkali with a concentration of less than 10% leads to the formation of a less stable tear film. The use of alkali with a concentration of more than 20% leads to a pH gradient and gel heterogeneity.

The compositions of the preparation of gels are presented in table. 2.

An example of the method will be shown using composition No. 4 as an example. 0.5 g of carbopol-10 powder is placed in the reactor, 5 g of a 10% aqueous solution of polyethylene oxide-400 are added with vigorous stirring, and then 70-90% of the total weight of purified water is added with stirring gel. Next, adjust the pH to a value of 6.0-7.0 with a 18% sodium hydroxide solution. Then, an alkaline stabilizer, preservative and antibiotic solution prepared in a separate reactor, is added to the composition with stirring by mixing aqueous solutions of benzalkonium chloride, edetate disodium and gentamicin sulfate, followed by the addition of an 18% sodium hydroxide solution. To the resulting mass is added ximedon in an amount of 4 g and a second time, if necessary, the pH is adjusted to the required value with an 18% sodium hydroxide solution. The resulting gel is sterilized for 1 h at a temperature of 80 ° C. Ready gel is packaged.

- 4 018202

On the basis of the eye departments of the GUZ NOKB im. Semashko was a study of the effects of the proposed drug. The following groups of patients were examined:

1) patients with dry eye syndrome;

2) patients with corneal injuries as a result of cataract surgical treatment (phacoemulsification + ocular lens implantation (IOL));

3) operated patients (the gel was used as a contact medium during laser operations);

4) patients with other eye diseases.

In the table. 3 presents data on the state of the precorneal tear film (PSP) in patients with symptomatic dry eye syndrome with contact correction (wearing contact lenses) before and after the use of Vidisik preparations and the proposed drug.

Observations were made of 22 patients aged 19 to 54 years, of which: women - 16, men - 6. Patients were divided into 2 equal groups. Group 1 - treatment with Vidisik; Group 2 - treatment with the proposed drug. All patients selected for the study were observed earlier and were examined again before using the drugs, 2 weeks and 1 month after their use.

Traditional ophthalmological research methods were used: visometry, refraction determination, ophthalmometry, examination of the condition of the eyelids and anterior segment of the eyeball using lateral illumination, biomicroscopy of the anterior segment of the eyeball and optical media, ophthalmoscopy. To study the state of PSP, the time of its rupture was determined (test according to M.8. Νογπ, 1969), the state of the lacrimal meniscus was evaluated. The quantitative composition of the SRP was determined using a Schirmer test. The state of the corneal epithelium was evaluated after installation of a 1% fluorescein solution. Studies have shown that the proposed drug forms a stable tear film of sufficient viscosity, smoothing out unevenness of the cornea, and has a prolonged effect. The drug is not inferior to the traditionally used gel-based tear substitute Vidisik. Both drugs are effective in the treatment of postoperative transient dry eye syndrome.

A qualitative difference between the drug according to the invention from the drug Vidisik is the presence of xymedon in its composition. The mechanism of action of xymedon is to stimulate the process of regeneration of the epithelium. The proposed drug, in addition to moisturizing, smoothing the surface of the cornea, helps to accelerate the epithelization of the cornea in the postoperative period. The timing of epithelization and the quality of the epithelium affect the transparency of graft engraftment.

In the table. 4 shows comparative data on the use of ophthalmic gels Vidisik, Korneregel, Actovegin and the gel according to the invention after cataract surgery with a corneal incision (phacoemulsification + IOL). As a rule, after surgical treatment, the integrity of the nerve endings is violated, which leads to a violation of tear production and congruence of the surface of the cornea and eyelids.

The criteria for the clinical effectiveness of the treatment were epithelization of the corneal incision, the disappearance of corneal edema, improvement of vision, etc.

This study found a pronounced positive effect of the drug according to the invention on the course and outcome of the postoperative process. Compared with other gels, in the treatment with the proposed drug, a decrease in edema was noted, which contributed to a shortening of the relief of the inflammatory reaction, and a decrease in pain and corneal syndrome. In a shorter time, corneal incision epithelization occurred; in the control group of patients without the use of drugs, corneal epithelization proceeded much more slowly. It should be noted that due to the stimulation of the processes of migration of epithelial cells under the influence of the proposed drug, an earlier re-epithelization of the wound surface occurs, the gates for infection are closed and the percentage of transparent healing of the cornea increases.

The preparation according to the invention was also used when performing laser operations as a contact medium. Comparison drugs used Vidisik and Oligel. In the table. 3 shows the comparative results of the use of drugs as a contact medium when performing laser operations. Studies have shown that the drug proposed in the invention has optimal viscosity and meets all the requirements for this group of drugs.

A clinical study was also conducted of the local application of the preparation according to the invention for corneal erosion and traumatic keratitis (11 eyes), eye burns (5 eyes), epithelial endothelial corneal dystrophy (10 eyes), and herpetic keratitis (4 eyes).

In the treatment of erosion and traumatic keratitis, the use of the drug in combination with the main complex increased the effectiveness of the treatment. Epithelization of corneal defects with this pathology occurred on 3-5 days. Acceleration of epithelization compared with the control group of patients receiving the drug Vidisik, was 3-4 days. With superficial traumatic keratitis, corneal opacities were not observed. With deep keratitis in both groups, the outcome of the process was turbidity of varying degrees of intensity, but during treatment with the drug according to the invention, turbidity was

- 5 018202 non-intense, mainly in the form of a cloud. The purpose of the drug did not cause adverse and allergic reactions.

A pronounced positive effect of the drug on the course and outcome of the burn process was established. This drug, combined with complex treatment, helped to reduce the severity and shorten the timing of the relief of the inflammatory reaction, which was manifested in a decrease in pain and corneal syndromes, edema and descemetitis. Patients in a shorter time came complete epithelization of the burn surface. The terms of epithelization, depending on the severity of the burn, are from 3 to 16 days, whereas in the control group when using Vidisik they were from 6 to 24 days.

In epithelial-endothelial dystrophy, the drug was used in combination with soft therapeutic contact lenses. In the presence of bullous changes in the cornea, it is advisable to use therapeutic contact lenses, while wearing them, a gradual flattening and reduction of the bullous elements occurs. Then it is possible to cancel the therapeutic soft contact lens with the simultaneous administration of disinfectants in combination with the drug according to the invention. The purpose of this drug led to the epithelization of defects in the epithelium and to a significant improvement in the condition of the surface of the cornea. Patients noted a decrease in pain and corneal syndromes, and in some cases the complete disappearance of painful sensations. The positive effect of the drug is very valuable in case of loss of the lens by the patient and the impossibility of its quick replacement or in other circumstances when it becomes necessary to cancel the contact lens.

With herpetic keratitis, the drug was used only as an addition to specific treatment. However, in cases of superficial herpetic lesions, its effectiveness was quite pronounced: the end of epithelization occurred at the end of the first week of treatment.

It should also be noted that the subjective tolerance of the drug by patients is good, in none of the cases of its use was there any deterioration or blurred vision, redness of the eyes or pain. All patients noted a decrease in pain and photophobia, which was not characteristic of treatment with Vidisik.

Thus, the proposed ophthalmic gel, which includes Xymedon, shows the necessary qualities of homogeneity, uniformity, viscosity, osmolarity, thixotropy on the surface of the eyeball and provides the functions of rehydration, keratoprotective and reparant.

Table 1

Characterization of the technological process for the preparation of gels based on carbopol

Example No. Polymer grade Swelling 10-30% solution of polyethylene glycol Complete homogenization time Viscosity without Xymedon mRac The viscosity of a 0.5% solution in the presence of a 5% solution of Xymedon mPa-s one I11geg-20 ^a) - 20-30 min 25 fifty υΐΐτεζ-20 ⁶⁾ 3 min PEO-400 (thirty%) 10-15 minutes 25 fifty 2 I11geg-21 ^a) - 20 minutes 25 fifty ikgeg-21 ⁰⁾ 3 min PEO-1500 (twenty%) 15 minutes 25 fifty 3 Shgeg-10 ^a) 40 min 25 55 Shgeg-10 ^&) 5 min PEO-1500 (twenty%) 20 minutes 27 55 4 SAGORO1 - 980 ^a) SAGORO1980 ° 5 min PEO-bOOO (10%) 60 min 30 min 25 55

a) 2.5 g of powder was sprayed onto the water surface of the water, after the powder was completely wetted, then 500 ml of water was added with stirring;

b) 2.5 g of the powder was wetted with 30 ml of a 10-30% solution of polyethylene oxide, then 220 ml of water was added with stirring.

- 6 018202

table 2

No. Preparation of an acidic hydrophilic base Base thickening Xymedon% PH correction polymer wt.% polymer Polyethylene oxide wt.% pH C% (LaOH) solution pH one. Sagorog 980 0.5 PEG-400 5.0 (30%) 5,0 eighteen 7.0 5,0 7.3 2. SAGOROG twenty 0.3 PEG-1500 3.0 (16%) 5.3 10 6.8 10.0 7.4 3. Sagorog 940 1,0 PEG-6000 10.0 (10%) 4,5 eighteen 6.9 5,0 7.3 4. Sagorob 10 0.5 PEG-400 5.0 (10%) 5,0 eighteen 7.1 4.0 7.3 5. SAGOROG 10 0.5 - 5.3 8 7.0 3.0 7.4

The concentrations of benzalkonium chloride (0.01%), trilon B (0.004%) and gentamicin sulfate (0.02%) remained constant in these examples.

Table 3

The state of the precorneal tear film (PSP) in patients with symptomatic dry eye syndrome with contact correction before and after the use of drugs

The timing observations PSP gap time according to Νοπι, (sec) Schirmer-1 test, (mm) Lacrimal meniscus (mm) Vidisik The preparation according to the invention Vidisik The preparation according to the invention Vidisik The preparation according to the invention Source 3 ± 0.8 3.2 ± 0.9 7.5 ± 0.9 7.8 ± 1.0 0.N0.02 0.1 ± 0.01 2 weeks 8.3 ± 1.2 8.4 ± 1.0 9.2 ± 1.5 10.0 ± 1.4 0.3 ± 0.04 0.3 ± 0.03 1 month 13.1 ± 1.4 14.2 ± 1.3 15.0 ± 0.2 15.2 ± 0.5 0.3 ± 0.04 0.3 ± 0.03

Table 4

Comparative data on the use of drugs after phacoemulsification + IOL cataract with the presence of a corneal incision

Vidisik

Corn Rig

Actovegin

Men

Women

Age

Average age

Operation

Epithelization of the corneal section. Corneal edema in the tunnel area on the first day

Lack of corneal edema in the area _____ tunnel _____ Concomitant treatment U18i5 upon admission

56-75

65.4 people - 1st day 5 people - 2nd day 1 patient ++++ 5 patients +++ 10 patients ++ patient + On average 4-5 days

Reg. 1.seg1a-0.2

0.2-0.9

55-81

60-78

66.9

Phacoemulsification + IOL people - 1st day 4 people - 2nd day patient ++++ 4 patients +++ patients ++ patients + On average 3-4 days people - 1st day people - 2nd day 2 patients ++++ patients +++ patients ++ patient + On average 4-5 days

1. Chloramphenicol 1 drop 4-6 times a day

2. Naklof-1 drop 4-6 times a day

Rg.1.sePa-0.3

Reg. 1.seg1a-0.2

The preparation according to the invention 8

58-82

66.2 people - 1st day 3 people - 2nd day 7 patients +++ patients ++ patient +

3 days on average

Reg. 1.seg1a-0.2

0.2-1.0

Table 5

Comparative data on the use of drugs as a contact medium for laser operations

Estimated Parameters Vidisik Oligel The preparation according to the invention Transparency complete complete complete Viscosity insufficient increased optimal The presence of reactive edema not sometimes not cornea The need for instillation It is necessary to wash the conjunctival Not antibacterial drugs cavity with antibiotic solution the need after surgery

CLAIM

Claims (2)

1. An ophthalmic gel containing 0.2-1.0% rare crosslinked polyacrylic acid and / or its derivatives containing a carboxyl group, preservatives, stabilizers, a drug from the reparant group, purified water, and having a pH value within the pH of the tear fluid, characterized in that 1- (β-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-hydroxypyrimidine (xymedon) is used as a medicinal substance and additionally contains an aqueous solution of polyethylene oxides, sodium hydroxide in an amount sufficient to obtain a gel with pH 6.0-7.9, in ka ETS preservatives and stabilizers comprising benzalkonium chloride, disodium edetate and aminoglycoside antibiotic - gene - 7 018202 tamycin sulfate in the following ratio of components, wt.%: rare crosslinked polyacrylic acid and / or its derivatives containing a carboxyl group of 0.2-1.0; 10-30% aqueous solution of polyethylene oxide 2-10; Xymedon 1-10; benzalkonium chloride 0.005-0.015; disodium edetate (Trilon B) 0.002-0.004; gentamicin sulfate 0.02-0.03; purified water - up to 100. 2. The method of preparation of the gel according to claim 1, which consists in the fact that with vigorous stirring in a dry powder of the crosslinked polyacrylic acid and / or its derivatives containing a carboxyl group, an aqueous 10-30% solution of polyethylene oxide taken in tenfold excess by weight of relative to the powder, then 70-90% of purified water of the total gel mass is added with stirring, after which the pH is adjusted to a value of 6.0-7.0 with sodium hydroxide solution, then, previously prepared in a separate reactor, is added with stirring Christmas-tree solution of a stabilizer, preservative and antibiotic by mixing aqueous solutions of benzalkonium chloride, disodium edetate and gentamicin sulfate, followed by the addition of 10-20% sodium hydroxide solution, after which xymedon is added in a mass concentration of 1-10% and the pH is adjusted again to the required value of 10- 20% sodium hydroxide solution, the resulting gel is sterilized.