Method of eye treating burns

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and is intended for treatment of eye burns. For this purpose instillations of eye drops of 2% of mexidol solution in conjunctival cavity is carried out 2-4 times per day immediately after burn and during the following two weeks.

EFFECT: chosen concentration of mexidol and mode of introduction in claimed method ensure effective treatment of burns at early terms after trauma, including by normalisation of activity of enzymes and proteins, which take part in processes of reparation and regeneration, fast growth of vessels and recovery of microcirculation, as well as prevention of formation of deep ulcers of cornea.

9 dwg, 6 ex

 

Treatment of burn injury to the eye is important socially significant problem, because at the present time, the frequency of eye burns constantly growing, burn the eye disease is difficult to treat and often leads to disability of young people of working age.

Ulceration of the cornea, caused by burns eyes, is the leading cause of vision loss as a result of this injury. Significantly affects the course of reparative process occurs after burn ischemia of the conjunctiva, which hinders the healing process and often leads to the need for surgical excision of the area of necrosis. Therefore, one of the most important tasks in medical treatment of eye burns is to prevent or reduce the intensity of corneal ulceration and restoration of microcirculation in the conjunctiva.

In complex medical treatment of eye burns use antibacterial and antiseptic pharmaceuticals, antiprotease-static agents, antioxidants, antihypoxants, funds that have a regenerative effect and improves microcirculation (Rational pharmacotherapy in ophthalmology // Ed. by E.A. Egorova. M: Litter. 2006. S-657; Morozov V.I., A.A. Yakovlev // Pharmacotherapy of eye diseases. M: Medpress-inform. 2009. S-179).

When traumatic tissue damage, including the number of the e tissues of the eye, there is a rearrangement of various metabolic processes, such as proteolytic and free radical aimed at cleansing the wound, but at the same time serving as a reason for the expansion of the damage zone. Is the depletion of the pool of endogenous antioxidants that accompanied the emergence of the so-called oxidative stress (Zenkov NICHOLAS, Lankin old Testament, Menshchikova E.B. Oxidative stress // MAIK "Nauka/Interperiodica". M. 2001. 343). Free radicals damage the membrane structure of cells, structural and functional proteins, aggravate the violation of microcirculation, resulting in injury. Violation of microcirculation in the tissues lead to insufficiency of the tissues, the development of tissue hypoxia, which simultaneously contributes to the increased oxidative stress. Therefore, for the treatment of wound healing, it is advisable topical application of antioxidants and antihypoxants. However, there is an insufficient number of antioxidant drugs and antihypoxant action for topical application in the eye burns.

There is a method of treatment of burns of the eye by subconjunctival injection of antioxidant echinochrome ("Histogram") (EN 2038088, 1995). Shows the effectiveness of local application as antioxidant therapy emoxipin and pyridoxine (Arkhipova LT, Dolgova I.G. Prognostic significance IU is the shaft and the system of indicators of lipid peroxidation and antioxidant system in penetrating eye injuries and their dynamics on the background of the topical application of antioxidants, " Vestn. ophthalm. 2001. No. 5. Pp.37-40).

Injuries and burns to the eyes are the indication for the drug Erised, active principle of which is the antioxidant enzyme superoxide dismutase, which is available in powder form for the preparation of eye drops, as in solution, the enzyme rapidly loses activity, which is inconvenient in use (instructions for use).

On the basis of L-carnosine developed eye drops Sevitin, one mechanism of action is inhibition of lipid peroxidation, and the indications for its use are injuries of the cornea of various etiologies (instructions for use).

For wound healing of the cornea is proposed to use the antihypoxants that reinforce energieproductie in the cell in the system of mitochondrial oxidative fosforilirovanija. To antihypoxant drugs include succinatecontaining and buccinatoria funds. Shown a positive effect of succinic acid on the course of the wound process in the eye (Brzeski CENTURIES, Golubev HE, Shumakova PHD, Savateeva T.N., Kovalenko A.L. Study of the effectiveness of the drug Optalgin in the treatment of wounds of the cornea in the experiment // Sat. Tr. II Euro-Asian conference. in ophthalmic surgery, Ekaterinburg. S-196; Rumyantseva O.A. Kuznetsov S.L., Spivak I.A., Rumyantseva A Comparative evaluation of the effect of steroid hormone is in, and salts of succinic acid on the regeneration of the cornea after photorefractive keratectomy // proc. Dokl. proc. Proliferative syndrome in ophthalmology. M. 2002. P.101-102). Known eye drops Cratonic containing sodium succinate, as well as modifications of these drops (Patent No. 212825 from 20.11.1998, Patent No. 2127099 from 10.03.1999).

As follows from the above data, eye drops for the treatment of eye burns with antioxidant or antihypoxant action, there is currently very little, no drugs, while providing antioxidant and antihypoxant action, i.e. the combination of properties which are available for Months.

The closest analogue. Eye drops Emoxipin 1% is recommended for the treatment of eye burns (instructions for use). The emoxipin (methylethylidene hydrochloride) in the form of eye drops is widely used in ophthalmology. Indications for use Emoxipin in the form of eye drops are inflammatory processes in the cornea, including those caused by burn trauma, hemorrhage in the anterior chamber of the eye, treatment of complications of myopia, protection of the cornea when wearing contact lenses.

At the same time, some studies have shown poor efficacy of emoxipin in the treatment of eye burns (Travkin A.G., Shulgin N.A. Comparative evaluation of oxidant and antioxidant system of blood in rabbits with alkali burns of the eye in the treatment of antioxid ntmi // Vestnik St.Petersburg University. ophthalm. 2004. No. 5. P.26-28). There is evidence of weak antioxidant activity of emoxipin (Babenkov IV, teselkin CREATING, Makashov, NV, Guseva MR Antioxidant activity of histogram and some other drugs used in ophthalmology, " Vestn. ophthalm. 1999. No. 4. S-24).

Mexidol is fundamentally different from Emoxipin the fact that he is succinatecontaining derived 3-hydroxypyridine. Being derivatives of 3-hydroxypyridine, these drugs are structurally similar to compounds of the group of vitamin WB, which are necessary components of key enzymatic processes involved in the metabolism of amino acids and biogenic amines, which largely determines the biological properties of MEK-Sigala and Emoxipin. Antioxidant properties of oxypyridine determined by the polarity of IT. Antioxidant properties of Mexidol due to several of its features: it can interact with ions of Fe2+with a water-soluble radicals, including superoxide anion, is able to increase the efficiency of the endogenous antioxidant system (Lukyanova L.D., Romanova V.E., Chernobaev's arrangement G.N., Lukins NV Features antihypoxic action of Mexidol associated with its specific effect on energy metabolism. Chimpharm. magazine.-1990. No. 8. P.9-11.). Antihypoxic properties of Mexidol associated with the presence of the it succinates radical. Succinate, which is an integral part of Mexidol (which distinguishes it from Emoxipin), is among the substrates of the Krebs cycle, which provides the basic energy needs of the organism that determines antihypoxant properties derived hydroxypyridine. Succinate own bad passes through tissue barriers, but the pyridine base facilitates entry of succinate through the cell membrane.

Mexidol comes in the form of a solution (5%) for intravenous and intramuscular injection and tablet form. He has found wide application in medicine as neuroprotective agents, antihypoxic drug and antioxidant, providing energotropic effect in ischemic conditions and metabolic disorders. A pronounced therapeutic effect of Mexidol in cardiovascular, neurological diseases, according to experimental studies T.A. Voronina, is determined by the fact that the drug is a substance "cocktail"type, combining different effects.

The use of Mexidol in the form of eye drops for the treatment of traumatic process in the eye, including burns of the eyes, seems very promising, since this product combines the antioxidant properties antihypoxant.

Mexidol, available in tablets Lakers the governmental form and in the form of solution for injection, widely and successfully used in various fields of medicine. In neurology and psychiatry, it is used as a means nootropic and anti-ischemic actions (Voronina T.A. Antioxidant Mexidol. Basic drugs is got with the effects and mechanism of action. // Psychopharmacology and biological narcology. - 2001. No. 1, pp.2-12). In cardiology shows that Mexidol improves the course of myocardial infarction, accelerates the stabilization of angina (hazura, V.V., Pichugin CENTURIES, Sarnow L.N., Smirnov L.D. anti-ischemic cardioprotective effect of Mexidol. //Cardiology. 1996. No. 11. P.59-63). Mexidol used to damage tissue structures of the body of various etiologies (Novikov V.E., Kovalev L.A., Lisenkova C.O., klimkina H. Pharmacology of antioxidants on the basis of 3-oksipiridina. // The Bulletin Of The Smolensk Good. Acad. 2004. No. 1). Application after gynecological surgery reduces inflammation and improves the repair of surgical wounds. The efficiency of Mexidol for the treatment of erosive-ulcerative lesions of the gastroduodenal zone, peritonitis. Found hepatoprotective properties of Mexidol. In surgery Mexidol is used for local treatment of purulent wounds, which are made dressings with immobilized Mexidol, with this method of application of Mexidol shows the decrease in peroxide Oka is of lipids. On the model of ischemia of the skin demonstrated antihypoxic and antinecrotic effect of Mexidol, which the authors attributed to the increase in activity of antioxidant enzymes, enhancing energy security. As anti-inflammatory agents Mexidol has been successfully used in dentistry.

In ophthalmology Mexidol in the systemic use in patients with eye diseases degenerative origin contributed to maintaining or expanding the field of view (Malyshev V.E., I. Salnikov the Experience of using the drug "Mexidol in comprehensive outpatient treatment of patients with eye diseases degenerative origin // bull. the experts. bioli honey. 2006. Appendix 1. P.55-57). There is data on the effectiveness of systemic use of Mexidol in the complex treatment of acute posttraumatic uveitis (Marcheva NM, Panova IE, Grafova T.V. Clinical efficacy Mexidol in the complex treatment of acute posttraumatic uveitis and its impact on the performance of local hemodynamics in patients with penetrating wound of eyeball//BORN. 2012. V.5. No. 1. P.51-56).

In ophthalmology locally Mexidol was injected into the lymphatic region of the orbit for the treatment of postoperative complications after cataract extraction (Patent RU (11) 2290203 (13) C1 from 2006.0627.

Patented tool for the prevention and treatment of ophthalmologic diseases, which is a gel and contains Mexidol (Patent (19)RU (11)2359658 (13)C1). However, in the available sources we have not found any information about the effectiveness of its application in ophthalmology, including burns of the eye.

We have shown that instillation of eye drops Mexidol accelerate the repair of epithelial wounds of the cornea in the rabbit, enhancing the proliferation of the epithelium, and that Mexidol shows high antioxidant activity against superoxide anion radical and hydroxyl radical as in the model system, and in the tear fluid (Chesnokov NB, Beznos O.V., Pavlenko T.A., Soboslai A.A., Pavlov M.V. Antioxidant properties of Mexidol eye drops and influence their local application on epithelial wound healing of the cornea in the experiment // BORN. 2012. V.5. No. 1. P.88-91).

Mexidol has extremely low toxicity, and when introduced into the conjunctival SAC impossible to achieve as LD50and the threshold toxic dose.

The present invention is the use of eye drops Mexidol 2% for the topical treatment of burns of the eye.

The technical result of the invention is the reduction of the inflammatory response, acceleration of healing of burn wounds, warned the e development of deep corneal ulcers and accelerate the recovery of microcirculation after burns of the eye.

The technical result is achieved due to local injection in the eye of Mexidol in the form of 2% eye drops 2-4 times a day for 2 weeks after the burn.

To study the action of eye drops Mexidol 2% on the healing of burn wounds of the cornea we have conducted two series of experiments.

I series. Comparative evaluation of the effect of applying the eye drops Mexidol and Emoxipin, and placebo on the clinical course of reparative and local metabolic after burn center area of the cornea in rabbits.

In 15 (30 eyes) rabbits modeled dosed alkaline burn center area of the cornea by application to the cornea of the circles of fabric (010 mm)impregnated with 0.1 N NaOH, 40 sec. This burn is deep damage to the corneal stroma, leading eventually to the development of ulcers. Comparative assessment of the impact of applying the eye drops Mexidol and Emoxipin, and placebo (3 times a day for 28 days starting with the first day after burn) on the clinical picture of the disease, the antioxidant activity of the lacrimal fluid and the concentration of plasminogen.

group 1 - instillation of Mexidol - 5 rabbits (10 eyes);

group 2 - instillation Emoxipin - 5 rabbits (10 eyes);

group 3 - instillation placebo 5 rabbits (10 eyes);

group 4 - intact kr is the faces - 3 rabbits (6 eyes) to control the effects on biochemical indices of permanent external factors.

II series. Comparative evaluation of the effect of applying the eye drops Mexidol and Emoxipin, and placebo on the clinical course of reparative and local metabolic processes after combined burn of cornea and conjunctiva of rabbits.

In the second series in 15 (30 eyes) rabbits in the same way he modeled the combined alkaline burns of the cornea, conjunctiva and limbus, placing a circle of fabric so that half of it was on the cornea, and half of the conjunctiva. Such a burn leads to the development of post-burn ischemia of the conjunctiva. Comparative assessment of the impact of applying the eye drops Mexidol and Emoxipin (3 times a day for 14 days starting from the first day after burn), and placebo on the clinical picture of the disease, the antioxidant activity of the lacrimal fluid and the concentration of plasminogen and metabolites of nitrogen monoxide (nitrates and nitrites).

group 1 - instillation of Mexidol - 5 rabbits (10 eyes)

group 2 - instillation Emoxipin - 5 rabbits (10 eyes)

group 3 - installation placebo 5 rabbits (10 eyes)

group 4 - intact rabbits - 3 rabbits (6 eyes) (for control of biochemical parameters)

Involved 36 rabbits (72 eyes). The number of animals d is insufficient to perform statistical processing of the results.

Evaluation of the clinical manifestations of burn of eye disease was carried out on 4, 10, 14, 21 and 28 days after injury by biomicroscopy with staining with 0.5% solution of fluorescein. The values were expressed in arbitrary points established by the laboratory schema.

Fence tear fluid for biochemical studies were performed 1 day before applying the burn and then at 1, 3, 7, 14, 21 and 28 days after injury. Tear fluid was collected in the morning before the first installation of the drug with circles of filter paper 05 mm, which was placed in the lower conjunctival SAC for 5 min Components tears suirable saline solution.

Antioxidant activity against hydroxyl (AAO-HE-) and superoxide anion radicals (AAO-O2-) was determined by the parameters of the kinetics of chemiluminescence in the model system hemoglobin-peroxide-luminal (Gulidov O., Lubicky O., Klebanov GI et al. The change in antioxidant activity in the tear fluid during experimental burns of eye disease // bull. the experts. Biol. and medicine. 1999. T, No. 11. S-574.); the activity of plasminogen - spectrophotometric-ski with a specific substrate (Momot A.P., Mamaev A.N., Barkagan SS et al. Method for the determination of plasminogen and its diagnostic value. // Problems of Hematology. 1999. No. 1. P.17-20.); the content of nitrate and nitrite by reaction with a reagent Griss (Green L.C., Wagner, D.A., Glogowski J. et al. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluid. // Annal. Bio-chem. 1982. Vol.126. P.131-138.).

Studies have shown the following.

At a burn center area of the cornea:

1. Daily instillation of Mexidol in the first two weeks after burn injury of the Central region of the cornea resulting in significant losses, in terms of area and depth of the defect of the cornea. The use of Mexidol for a longer time reduces this effect and therefore impractical. The emoxipin during the first week of use does not affect the ulceration of the cornea, and further leads to broadening and deepening the defect of the cornea compared with the placebo effect.

2. Mexidol enhances the expansion pericorneal vessels at a burn that can facilitate the penetration required for repair of blood components in the cornea. The emoxipin not affect pericorneal injection.

3. The emoxipin reduces inflammation of the conjunctiva at the beginning of the application, and Mexidol - two weeks installations. More prolonged use of Mexidol affects its anti-inflammatory effect on the conjunctiva.

4. The increase in antioxidant activity (mainly in relation to hydroxyl radicals) in the tear fluid of rabbits with a burn center area of the cornea under the influence and is stellazio Months compared with placebo. The increase in the content of hydroxyl radicals is one of the main factors of tissue damage by oxidative stress, developing inflammation. Therefore, the increase of antioxidant activity against hydroxyl radicals can be considered as one of the causes of the favorable effect of Mexidol on the healing of burn wounds of the cornea.

5. Instillation of Mexidol in the treatment of burns of the eye, leading to corneal ulceration, increase the content of plasminogen in the wound during the first 3 days after burn, helping to cleanse wounds. Installation Emoxipin increase the levels of plasminogen in the wound at day 7 after burn, contributing to the activation of proteolytic enzymes that destroy the structural proteins of the cornea, and therefore the strengthening of ulceration of the tissue.

When combined with the burn of cornea and conjunctiva:

1. Installation of eye drops Mexidol contribute to a more rapid recovery of microcirculation in the conjunctiva after her burn. Compared with Emoxipin Mexidol has a stronger anti-ischemic effect.

2. Instillation of eye drops Mexidol reduce the degree of ulceration of the cornea when it burns, and instillation of Emoxipin increase.

3. There was an increased antioxidant activity (mainly in relation to the hydroxyl radical is in the tear fluid of rabbits with combined burn of cornea and conjunctiva under the influence of installations of Mexidol in comparison with placebo. The emoxipin less than Mexidol, contributed to maintaining normal levels of antioxidant activity.

4. When combined with the burn of the cornea when it is noted extensive ischemia conjunctiva, instillation of Mexidol lead to increased levels of plasminogen in the tear fluid, which in the early stages contributes to the removal of necrotic tissue. Increased levels of plasminogen at a later date due to increased under the effect of Mexidol blood supply in the conjunctiva.

5. Mexidol increase the local content of nitrogen monoxide in the burn wound of the cornea and conjunctiva, which could explain its anti-ischemic effect.

Examples

Example 1. Rabbit No. 3. Corneal burns, instillation of 2% of Mexidol.

After burn of the cornea develops an inflammatory reaction of the conjunctiva of the eyelids and the eyeball, which is expressed in edema and hyperemia of the conjunctiva and the appearance of the discharge, at first serous, then purulent. Rabbit No. 3 these symptoms grew up to 28 days, the amount of discharge and injection of the conjunctiva (the overflow of blood in the blood vessels of the conjunctiva of the eyeball) was decreased only after 21 days. To 7 days to become noticeable newly formed blood vessels growing into the cornea from the limbus is corneal neovascularization. Vessels RA is here towards the center of the cornea, as you increase the length of their density decreases. The intensity of neovascularization reached a maximum at 14 days (6 points), then decreased to 4 points. Directly after burn the surface of the cornea is devoid of epithelium. During the first 3 days he recovered, but then again rejected, and develops first erosion (epithelial defect), and then the plague (stromal defect) of the cornea. Rabbit No. 3 intensity ulceration of the cornea (increased surface area and depth of the defect) was increased up to 21 days (5 points), and on day 28 was reduced to 3 points (Figure 1). The area of the defect was maximum at 21 days (2.5 points), and depth - for 14-21 days (2 points).

As it was established by us in previous studies, with any inflammatory process in the eye antioxidant activity of the lacrimal fluid is reduced in the first day and remained below normal. In this case, the instillation of 2% of Mexidol AAO-HE-for all 28 days remained above normal with rises by 35% for 3 and 14 days (Figure 2). Marked 3 increase the AOA-O2-: 3 day (40%), 14 days (30%) and 28 days (66%) (Figure 3).

Had elevated levels of plasminogen on the 3rd day (25%), followed by a gradual decline to normal by 14 days and 15% below normal at 28 days (Figure 4). This indicates activation at the early stage of burn the howl of the disease plasmin, which in this period helps to cleanse the wound of necrotic tissue and prepare it for subsequent regeneration. The fall of the level of plasminogen after 3 day talking about the timely reduction of enzyme activity after the task is completed.

Example 2. Rabbit No. 6. Corneal burns, instillation of 1% Emoxipin.

Swelling and redness of the eyelids, conjunctival injection increased with progression of burn disease and persisted up to 28 days. The intensity of neovascularization of the cornea gradually increased up to 21 days (4.5 points) and then not changed. The intensity of corneal ulceration was growing up to 14 days (5 points), after 21 days decreased to 3 points, but complete closure of the defect within 28 days has not occurred (Figure 1). The area of the defect was maximum at 21 days (2 points), and depth - 14 (2.5 points).

For all 28 days of the AOA-HE-retained values close to normal, but on the 14th day, when the intensity of corneal ulceration, reached a maximum, the AOA-HE-decreased by 40% (Figure 2). On the 3rd day after burn marked the rise of the AOA-O2-at 55%, then it decreased to values below normal and exceeded the normal level only at 28 days (Figure 3).

There were two level rise plasminogen: on day 7 (31%), and at 28 days (21%) (Figure 4). Increased activity of plasmin in the period, when is the regeneration of the corneal stroma, leads to the destruction of proteins stroma and the development of deep ulcers that we have observed for 14 days after burn.

Example 3. Rabbit No. 11. Corneal burns, instillation of a placebo.

The signs of inflammation of the conjunctiva swelling and redness of the eyelids were pronounced, grew up to 28 days with a maximum of 14 days. Up to 28 days was observed abundant purulent discharge. At 14 days had a maximum intensity of neovascularization (5.5 points). The intensity of ulceration was also maximum at 14-21 days (4 points), then declined slightly (3 points) (Figure 1). The area of the defect was the highest at 14 days (2 points), depth 21 days (2 points).

AAO-HE-for all 28 days remained below normal 15-20%, which is characteristic of inflammation in the anterior segment of the eye in the absence of medical correction (Figure 2). AAO-O2-increased by 30% for 3 days, then declined to 7, and after 7 days was gradually increased and at 28 days exceeded the norm by 140% (Figure 3).

There were two small increased activity of plasminogen 1 (18%) and 7 (14%) day (Figure 4).

Example 4. Rabbit No. 20. Combined burn of cornea and conjunctiva, instillation of 2% of Mexidol.

The signs of inflammation of the conjunctiva were maximally expressed at 3-8 days after burn and completely disappeared by 21 days. Injection of the conjunctiva and corneal edema t is the train disappeared completely to 21 days. The circulation in the limb area has recovered to 14 days. The area and depth of the defect of the cornea with such burns are usually small. Rabbit No. 20 they reached a maximum at 10 days (1 point), at 21 days the defect is completely closed. Immediately after the burn part of the conjunctiva, which were impregnated with alkali fabric, becomes completely white - it is a zone of treatment of ischemia. Then it is gradually decreasing due to growing into her vessels from intact conjunctiva. Rabbit No. 20 the area of ischemia to 10 days decreased from 3 to 0.5 points, to 14 days circulation has fully recovered (Figure 5).

AAO-HE-1 through 14 days was below the norm by 25-30%, but at 21-28 day was above normal at 16-18% (Fig.6). AAO-O2-contrary , was always above normal and only for 14 days decreased to normal levels. At 28 days exceeding reached 40% (Fig.7).

The level of plasminogen significantly increased twice: 1 day in 2, 3 times and 21 days 2.7 times (Fig).

The content of nitrite and nitrate was increased from 1 to 7 days up to 140% of normal, then on the 14th day declined, but on 21 again exceeded the norm by 25% (Fig.9). The high content in the tear metabolites of nitrogen monoxide testifies to the active growth of blood vessels and the restoration of microcirculation in the area of the burn.

Example 5. Rabbit No. 26. Combined burn of cornea and conjunctiva, in which Tilletia 1% Emoxipin.

The maximum degree of inflammation of the conjunctiva was observed with 1 to 10 days and then gradually decreased. At 28 days of signs of inflammation were not. Injection of the conjunctiva was maximum at 4 days (3 points), then quickly fell and 21 days disappeared completely. Corneal edema is also completely disappeared to 21 days. The circulation in the limb area has recovered to 14 days. Maximum size and depth of the defect of the cornea was observed at 10 days (1 point), at 21 days the defect is completely closed. The area of ischemia for a period of from 4 to 10 days decreased from 3 to 1.5 points, to 14 days up to 0.5 points, and 21 days the blood circulation in the damaged area of the conjunctiva has fully recovered (Figure 5).

AAO-HE-during the whole experiment was 20-30% below normal, on the 14th day decline reached 50%at 28 days rate came back to normal (6). AAO-O2-during the first 7 days was slightly higher than the normal 14 day dropped to 15% below normal, and on the 28th day again exceeded the normal by 23% (Fig.7).

The level of plasminogen was increased by 20% for 1 day, then strongly reduced and only 21 days were above normal in 34% (Fig).

The level of metabolites of nitric oxide in the tear was increased by 20% for 3 days, then decreased and at 21-28 day again exceeded the rate of 45-50% (Fig.9).

Example 6. Rabbit No. 32. Combined corneal burns, konyu is for, instillation of a placebo.

Inflammation of the conjunctiva was most pronounced for 8 days, swelling and redness of the eyelids remained at 28 days. Corneal edema disappeared completely only at 28 days. Circulation in the area of the limb recovered at 28 days. The area and depth of the defect of the cornea maximum 10 day (1 point), at 21 days the defect is completely closed. The area of ischemia at 14 days was 0.5 points, to 21 days circulation has fully recovered (Figure 5).

AAO-HE-and for 21 days kept a very low value is 3 times lower than normal, and on the 28th day returned to normal (6). AAO-O2-during the first two weeks was above the norm by 16-17%, 14 days decreased to normal values, and to 28 again exceeded the norm by almost 40% (Fig.7).

The level of plasminogen in the tear was increased by 40% for 1 day, then decreased, and the maximum increase observed on the 14th day (2 times) (Fig).

The level of nitrates from the first day was below normal (7 days - 40%) and only at 21-28 day exceeded the norm by 20-35% (Fig.9).

Thus, the application of 2% of Mexidol in the first two weeks after burns of the cornea and conjunctiva helps to reduce the intensity of the inflammatory reaction, the reduction of the size and depth of the defect of the cornea, accelerated healing, and when burns of the conjunctiva - faster recovery of microcirculation in areas of the treatment of ischemia. A study of local metabolic processes showed that local application of 2% of Mexidol in the form of eye drops increases antioxidant activity of tears, promotes rapid cleansing of the wound due to the activation of proteolysis in the early stages after injury, strengthens education universal bioregulator of nitric oxide, which is a strong vasodilatation. Selected as the closest analogue of the Emoxipin not possessing these properties, indicating a greater efficiency of Mexidol in the treatment of eye burns.

The method of treatment of eye burns, characterized in that in the conjunctival cavity injected eye drops Mexidol 2% 2-4 times a day for two weeks after the burn.



 

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2 cl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and can be used for surgical treatment of progressing and complicated myopia. As scleroplastic material implanted is three-component complex, which contains mesenchymal stem cells, labeled with magnetic microparticles. Cells are translocated into biological or synthetic fine-porous material, which is tightly connected with polymer magnetic material with induction of constant magnetic field 1.5 mT, with multi-polar reversible magnetisation.

EFFECT: invention ensures enhancement of strength-elastic properties of sclera, stabilisation of myopic process with simultaneous prevention of development of dystrophic changes of eye fundus or further progressing in case of their presence.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and deals with treatment of acute optic neuritis. Method includes introduction of traumeel sublingually in dose 1 pill three times per day, lymphomyosot in dose 10 drops in 50-100 ml of water three times per day for 3 weeks. Also made are 10 injection cpurses of the following medications: traumeel in dose 2.2 ml every second day, cerebrum compositum in dose 2.2 ml two times per week with 3 day interval, coenzyme compositum in dose 2.2 ml two times per week with 3 day interval, hepar compositum in dose 2.2 ml two days per week with 3 day interval. Method includes carrying out hirudotherapy by application of 2-3 leeches on the region of temple and behind ears two times per week for two weeks.

EFFECT: method ensures recovery of vision acuity, elimination of absolute and relative scotomas, recovery of colour perception, normal picture of eye fundus, as well as elimination of all signs of inflammation, elimination of pain during movement of eye balls, improvement of health state.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: device refers to new styrene derivatives with the structure formula A in the form of geometrical isomers or tautomers and their pharmaceutical acceptable salts. In structural formula (A) R1 represents hydrogen; R2 represents hydrogen or C1-C6alkyl; R3, R4, R5 and R6 are identical or different and independently represent hydrogen, halogen, C1-C6alkyl or -OR12; R7 represents hydrogen or C1-C6alkyl; R8 represents hydrogen; R9 represents hydrogen, C1-C6alkyl, or -C(=O)R13; R10 represents hydrogen or C1-C6alkyl; Z represents W-Y, wherein W represents -C(R14)(R15)-; Y represents -C(R16)(R17)-; each R12 independently represents hydrogen or C1-C6alkyl; each R13 independently represents C1-C6alkyl; R14 and R15 are identical or different, and independently specified in hydrogen, fluoro, methyl, ethyl, trifluoromethyl, -OH, -OCH3 or -NH2; or R14 and R15 together form oxo; R16 and R17 are identical or different and independently represent hydrogen, halogen, C1-C6alkyl or -OR12. The other radical values are specified in the patent claim.

EFFECT: compounds may be used for treating an ophthalmic disease or disorder in an individual which can represent age-related macular degeneration or Stargardt macular degeneration.

17 cl, 14 tbl, 143 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, particularly to ophthalmology. An ophthalmic composition for treating keratoconjunctival damages and inflammations consists of an aqueous solution containing arabinogalactan 1 to 10 wt %, one or more preserving agents specified in a group consisting of sodium merthiolate, thimerosal, phenylmercuric nitrate or phenylmercuric acetate, phenylethyl alcohol, methyl-, ethyl-, propyl parabene, chlorhexidine acetate or gluconate or chlorobutanol, and containing no benzalkonium chloride. The ophthalmic composition is applied as a lacrimal substitute recommended for people wearing contact lenses.

EFFECT: group of inventions provides treating corneal erosions caused by wearing contact lenses.

16 cl, 5 tbl, 7 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology and can be used for treatment of open-angle glaucoma of I-II stages. For this purpose neuroprotectors are includes into standard complex of pharmacotherapy. As neuroprotectors used are 2-ethyl-6-methyl-3-hydroxypyridine succinate in dose 300 mg/day and picamilon in dose 150 mg/day.

EFFECT: method ensures expressed reduction of intraocular pressure up to its normalisation.

3 cl, 1 ex, 1 tbl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to an anti-cancer agent and an agent improving anti-cancer effect and combined with a liposomal agent prepared by oxaliplatin encapsulation in a liposome, and a combined therapeutic agent containing tegafur, gimeracil and oteracil potassium. The liposome in the declared agents consists of dipalmitoyl phosphatidylcholine, cholesterol and 1,2-distearoyl-8n-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000; or hydrogenised soybean phosphatidylcholine, cholesterol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)- 2000; or dipalmitoyl phosphatidylcholine, cholesterol and 1,2-distearoyl- sn-glycero-3-phosphoethanolamine polyglycerol. The invention also refers to using the above liposomal agent for preparing the anti-cancer agent and for intensifying anti-cancer activity of the combined therapeutic agent containing tegafur, gimeracil and oteracil potassium. Also, the invention relates to a method of treating cancer by administering the liposomal agent comprising oxaliplatin encapsulated in a liposome, and the combination drug containing tegafur, gimeracil and oteracil potassium.

EFFECT: group of inventions enhances anti-cancer activity of the therapeutic agent without toxicity increase.

12 cl, 10 dwg, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine, and concerns the use of a monobactam antibiotic of formula

,

wherein an oxyimino group, i.e. >C=N-O-, is Z-oriented, or a pharmaceutically acceptable salt thereof for preparing a therapeutic agent for treating a bacterial infection, in a combination with a carbapenem antibiotic specified in a group consisting of meropenem, imipenem, ertapenem and doripenem.

EFFECT: invention provides the high clinical effectiveness.

24 cl, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound that is a complex of 3-(2,2,2-trimethylhydrazinium)propionate-2-ethyl-6-methyl-3-hydroxypyridinium disuccinate of formula: . Additionally, the invention refers to stable crystalline forms of the complex of 3-(2,2,2-trimethylhydrazinium)propionate-2-ethyl-6-methyl-3-hydroxypyridinium disuccinate, as well as to methods for preparing the above complexes.

EFFECT: what is prepared and characterised is the new compound which possesses antihypoxic and adaptogenic action, and also low toxicity and storage stability, and which can find application in medicine and veterinary science.

11 cl, 17 ex, 10 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine and is intended for treatment of chronic erosive gastritis, associated with Helicobacter pylori. Urease test with dental plaques is performed and if microorganisms are identified, 30-minute long gingival applications with metronidazol (Metrogyl Denta gel) are carried out for 3 days in addition to anti-Helicobacter therapy. Starting with the 4-th day patient brushes the teeth with toothpaste of "Mexidol" series, adding Metrogyl Denta gel in "a match head" amount. After 15 minutes oral cavity is rinsed with 0.02% chlorhexidine digluconate solution. Said procedures are carried out for a month and repeated a month before supposed aggravation in stomach.

EFFECT: method makes it possible to prolong remission terms.

1 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts wherein r represents 1; Ar is specified in and , R1 is specified in -COOR1a, -NHSO2R1b, -SO2NHR1d, -SO2OH, -O-CH(R1e)-COOH and tetrazol-5-yl, R1a represents H, -C1-6alkyl, -C1-3alkylenaryl, -C1-3alkyleneheteroaryl, - C3-7cycloalkyl, -CH(C1-4alkyl)OC(O)R1aa, or R1aa represents -O-C1-6alkyl or -O-C3-7cycloalkyl; R1b represents R1c; R1d represents -C1-6alkyl or -C0-4alkylenaryl; R1d represents -C(O)R1c or -C(O)NHR1c; R1e represents -C1-4alkyl; Y represents -C(R3)-, Z represents -N-, Q represents -C(R2)-, and W represents a bond; Y represents -N-, Z represents -C(R3)-, Q represents -C(R2)-, and W represents a bond; Y represents -C(R3)-, Z represents -N-, Q represents -N-, and W represents a bond; or Y represents -C(R3)-, Z represents -CH-, Q represents -C(R2)-, and W represents -C(O)-; R2 is specified in H, halogen, -C1-6alkyl, -C3-6dicloalkyl, and -C0-5alkylene-OR2b; wherein R2b is specified in H and -C1-6alkyl; R3 is specified in -C1-10alkyl and -C0-5alkylene-O-C0-5alkylene-R3b; and R3b represents -C1-6alkyl; X represents -C1-12alkylene-, where at least one group -CH2- in alkylene is substituted by the group -NR4a-C(O)- or -C(O)-NR4a-, wherein R4a is specified in H, -OH, and -C1-4aalkyl; R5 is specified in -C0-3 alkylene-SR5a, -C0-3alkylene-C(O)NR5bR5c, -C0-3alkylene-NR5b-C(O)R5d, -NH-C0-1alkylene-P(O)(OR5e)2, -C0-2alkylene-CHR5g-COOH and -C0-3alkylene-C(O)NR5h-CHR5i-COOH; R5a represents H or -C(O)-R5aa; R5aa represents -C1-6alkyl, -C0-6alkylene-C3-7cycoalkyl, -C0-6alkylenaryl, or -C0-6alkylenemorpholine; R5b represents -OH, -OC(O)R5ba, -CH2COOH or -OC(S)NR5bbR5bc; R5ba represents -C1-6alkyl, -OCH2-aryl or -CH2O-aryl; R5bb and R5bc independently represents -C1-4alkyl; R5c represents H; R5d represents H; R5e represents H; R5g represents H or -CH2-O-(CH2)2-O-CH3; R5h represents H; R5i represents -C0-3alkylenaryl; R6 is specified in -C1-6alkyl, -C0-3alkylenaryl, -C0-3alkyleneheteroaryl and -C0-3alkylene-C3-7cycloalkyl; and R7 represents H or together with R6 to form -C3-7cycloalkyl; where each ring in Ar and each aryl and heteroaryl in R1-3 and R5-6 are optionally substituted by 1-3 substitutes optionally specified in -C1-6alkyl, -CN, halogen, -O-C1-6alkyl, -phenyl, -NO2, wherein each alkyl is optionally substituted by 1-5 fluorine atoms; each carbon atom in X is optionally substituted by one or more groups R4b, and one group -CH2- in X may be substituted by -C4-8cycloalkylene- and -CH=CR4d-; where R4b is specified in -C0-5alkylene-COOR4c and benzene, where R4c represents H; and R4d represents -CH2-thiophen; each alkyl and each aryl in R1-3, R4a-4d and R5-6 are optionally substituted by 1-7 fluorine atoms; where aryl represents monovalent aromatic hydrocarbon having one ring or condensed rings, and contains 6-10 carbon atoms in the ring; and heteroaryl represents a monovalent aromatic group having one ring or two condensed rings, and having 5-10 atoms in large in the ring with one atom of the ring represents a heteroatom specified in nitrogen, oxygen and sulphur. Besides, the invention refers to a pharmaceutical composition based on the compound of formula

,

to a method for preparing the compound of formula (I), to intermediate compounds used in synthesis of the compound of formula (I), to the use of the compounds of formula (I).

EFFECT: there are prepared new compounds possessing activity of a type 1 angiotensin II (AT1) receptor antagonist and activity of neprilysin inhibition.

38 cl, 36 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely psychiatry, and may be used for treating subacute reactive depressive psychosis. That is ensured by prescribing a drug-induced therapy consisting of Paroxetin in a double daily dose of 25-50 mg per os for 30 days. Diazepam 20-22 mg is intramuscularly introduced twice a day for 30 days. Mexidol in a daily dose 400-450 mg is introduced intravenously drop-by-drop for the first 20 days, and than 450-500 mg per os in tablets for the following 10 days. 0.01% Timogen 1.2-1.3 ml is introduced intramuscularly once a day for 10 days. The drug-induced therapy is combined with a hyperbaric oxygenation therapy with overpressure 0.8-1.0 atmospheres at compression rate and decompression 0.1 atmospheres a minute. An isopression period makes 40 minutes 2 times a day for the first 10 days, and then once a day for the following 10 days.

EFFECT: invention enables achieving a manifested clinical effect ensured by the use of the given therapeutic scheme.

1 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition contains a biologically active substance presented by 2-ethyl-6-methyl-3-oxypyridine succinate sorbed on a polymer carrier which is presented by polybutylcyanoacrylate nanoparticles or lactic and glycolic acid copolymer nanoparticles, and pharmaceutically acceptable substances in the following proportions, wt %: polymer carrier - 0.1-10, 2-ethyl-6-methyl-3-oxypyridine succinate - 0.1-5, excipients - the rest.

EFFECT: composition is high-effective in treating paroxysmal conditions; it has mild side effects.

6 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely surgery, and may be used for treating acute thrombophlebitis of lower extremities. That is ensured by the subcutaneous introduction of a mixture containing lydase, heparin and novocaine within a first web space of a foot with underlying conventional therapy. It is added with the introduction of a medicated mixture containint 0.25% novocaine 30 ml; lydase 64 standard units; 1% emoxipin 1 ml; dexamethasone 2 ml; fraxiparine 0.6 ml (11400 IU), sodium adenoside-triphosphate 1 ml; cefotaxime 1 mg; nicotinic acid 2 ml into a dorsal and plantar direction, to a medial and lateral side from the Achilles tendon, as well as around a vein involvement wherein a pathological process of acute thrombophlebitis develops, and into interspinous ligaments of the L2-3-L3-4 lumbar vertebrae. The therapeutic sessions are performed every second day within a therapeutic course of 5-10 procedures to arrest the inflammatory process completely. The therapeutic course is applied once more in 2-3 months.

EFFECT: method provides higher clinical effectiveness, reduced risk of threatening complications and limited progression of the disease due to pathogenetically proved action of surface and deep lymphatic networks of the lower extremities with expected activation of the transcapillary exchange.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns the use of compositions for preparing a drug for treating or preventing zygomycosis. The compositions contains at least one iron-chelating compound. Also, the compositions may additionally contain at least one antimycotic agent. The iron-chelating compounds are represented by the compounds other than siderophore or xenosiderophore with respect to the given fungoid diseases, namely deferiprone and deferasirox. The antimycotic agents being parts of the compositions may contain polyene azol or echinocandin antimycotic agents.

EFFECT: inventions are used for treating or relieving the severity of the fungoid diseases.

3 tbl, 9 ex, 14 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and can be applied for cell therapy in case of different ophthalmopathologies, accompanied by dystrophic and atrophic processes as well. Three-component complex for cell therapy contains mesenchymal stem cells, labeled by magnetic microparticles. Cells are translocated into biological or synthetic fine-pore material, which in its turn is strongly fastened with polymer magnetic material with induction of constant magnetic field 1.5 mT, with multipolar reverse magnetisation.

EFFECT: invention ensures directed supply of stem cells to pathological nidus and holding stem cells for specified time with creation of possibility of giving complex any form, size and space configuration, suitable for extrascleral implantation to any area of eyeball or visual.

2 cl, 1 ex

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