Method of treating operated non-closed macular hole

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be sued in treatment of macular hole of retina after performed operation. For this purpose 60% solution of lornoxicam is used. Medication is instilled into conjunctival cavity of operated eye in dose 1 drop 4 times per day, during three weeks.

EFFECT: method ensures closing of macular hole in short term due to elaborated doses and mode of introduction of medication, first proposed in form of eye drops and ensuring in such application efficient suppression of inflammation processes in tissue of retina and stability of obtained result.

8 dwg, 1 ex

 

The invention relates to medicine, namely to ophthalmology, and can be used in the treatment of macular hole retinal.

For many years idiopaticescoe macular hole was considered to be almost incurable condition, accompanied by loss of Central vision. In 1991, Kelly and Wendel (Kelly N E, Wendel R T. Vitreous surgery for macular holes. Results from a pilot study. Arch Ophthalmol 1991. 109654-659) published the first report of successful surgical treatment of this disease.

The main modern surgical treatment of macular holes is vitrectomy pars-plana and in most cases applies to the removal of internal border membrane (MPI), the operation ends with gas tamponade. In 70-90% of cases surgical treatment leads to the closure of the macular hole. Complications of surgical treatment of macular hole include the formation of complicated cataract, iatrogenic retinal breaks, retinal detachment and reopening of macular holes, the formation of the Central and paracentral scotomas.

So far, the causes of gaps not fully installed. To date, more and more are finding evidence that the development of these States play an important role in inflammatory reactions.

Proinflammatory prostaglandin which belong to the first wave of the organizers of the inflammatory response. To initiate their biosynthesis is sufficient to activate phospholipase A2, the following steps cyclooxygenase (COX) and prostaglandins (figure 1). From prostaglandines depends spectrum synthesized by the cell prostaglandins and set then run the regulatory reactions. The increase in the concentration of proinflammatory prostaglandins activates the biosynthesis of proinflammatory cytokines and adhesion molecules, migration of cells from the bloodstream into the area of inflammation, i.e. initiating the inflammatory response.

According to modern concepts the cyclooxygenase is a multienzyme complex that includes a dioxygenase, isomerase and reductase, and other components. The cyclooxygenase is hemoproteins, localized to the endoplasmic reticulum near the release of arachidonic acid from membrane phospholipids. COX exists in the form of at least two types of COX-1 and COX-2. Their role in the transformation of arachidonic acid in normal and pathological conditions are different. COX-1 is a constitutive enzyme, i.e. synthesized under the influence of physiological stimuli and is present in cells constantly. COX-1 catalyzes the synthesis of prostaglandins, prostacyclin and thromboxane, which regulate vascular tone and intensity of the microcirculation, cell division mucosal infection is a rule-intestinal tract, excretory function of the kidneys and other COX-2 is inducible and proinflammatory isoform of the enzyme. It is expressed mainly by macrophages, fibroblasts, endothelial and smooth muscle of blood vessels. When inflammation of the concentration of this isoform of cyclooxygenase increases to 80 times.

Closest to the claimed method is a method of conservative treatment of macular holes proposed by Kurz P.A. and Kurz D.E. (Kurz PA, Kurz DE. Macular hole closure and visual improvement with topical nonsteroidal treatment. Arch Ophthalmol. 2009 Dec; 127 (12): 1687-8). They suggest the use of such non-steroidal anti-inflammatory drugs (NSAIDs), 0.5% Ketorolac tromethamine and 0.1% nepafenac.

The disadvantage of this method is that Ketorolac should be buried in the eye for 32 weeks (8 months), and nepafenac - 11 weeks (2.5 months). 6 weeks after the use of medicines is the recurrence of macular holes and swelling.

The objective of the invention is to provide a method of treatment of the operated of metacrawlers macular holes by reducing the duration of the instillation of the drug in the conjunctival cavity while maintaining high performance and stability of the result, namely the involution of retinal edema, closure of macular holes. This is achieved through a more pronounced suppression of the activity of COX 1 and 2 tipo is, reduce the production of interleukin-6 and NO, being aggressive mediators of inflammation, inhibition of the release of oxygen from the active cells. Also improves blood rheology, decreases the permeability of the vascular walls. As a result, significantly suppressed the inflammation process.

The technical result when using the invention, suppression of the activity of COX 1 and 2 types, reducing production of interleukin-6 and NO inhibition of the release of oxygen from the active cells, the expression inhibition of inflammation, reduction in the duration of treatment and the stability of the result.

The technical result is achieved in that in the method of treating operated metacrawlers macular holes, including the use of nonsteroidal anti-inflammatory drugs (NSAIDs), according to the invention as NSAIDs use 60% solution lornoksikama which is buried in the operated eye, 1 drop 4 times a day, for three weeks.

When the claimed method of treatment the duration of treatment is reduced due to the fact that lornoxicam operates more efficiently due to a longer half-life in contrast to Ketorolac, proposed prototype, which refers to preparations of short action. Ketorolac has weak anti-inflammatory activity, lornoxicam expressed. Inhibiting the activity of COX, lornoxicam affects many elements of the process of inflammation:

1. Prevents damage to cell structures, reduces capillary permeability, which most clearly limits the exudative manifestations of the inflammatory process (inhibition of lipid peroxidation, the stabilization of lysosomal membranes, preventing the release into the cytoplasm and in the extracellular space of lysosomal hydrolases).

2. Reduces the intensity of biological oxidation, phosphorylation and glycolysis, which leads to inhibition of the production of makroergov, required for the biosynthesis of substances, transport of fluid and metal ions through the cell membrane, and many other processes that play an important role in the pathogenesis of inflammation (reduction of energy inflammatory response). In addition, the effect on tissue respiration and glycolysis changes plastic currency, as intermediate products of oxidation and glycolytic reactions of substrates serve as building material for various synthetic reactions (for example, the biosynthesis of kinins, mucopolysaccharides, immunoglobulins).

3. Inhibits the synthesis of inflammatory mediators (histamine, serotonin, bradykinin, lymphokines, prostaglandins, complement factors and other nonspecific endogenous damaging factors).

4. Has cytostatic the definition action leading to inhibition of the proliferative phase of inflammation.

5. Has a braking effect on gemokoagulyatia (primarily on the inhibition of platelet aggregation), which is an additional, secondary factor anti-inflammatory effect: the decrease of intensity of coagulation in the capillaries of the inflamed areas prevent the disruption of the microcirculation.

Due to all these effects is called persistent suppression of inflammation, and consequently the disappearance of retinal edema and closure of the macular hole.

The proposed method for the treatment of metacrawlers or recurrent after Subtotal vitrectomy with removal of the VPM of the macular hole is carried out as follows. The patient within three weeks installeret in the conjunctival cavity of the patient eyes of a 60% solution lornoksikama 1 drop 4 times a day.

The invention is illustrated by figures 1-8. The figure 1 presents the scheme of the metabolism of arachidonic acid. Where 5 is WRITE - 5-hydroperoxidation acid; PGE2, PG, PGR - prostaglandins; The - thromboxane A2; LTA, LTB, LTS4, LT, LTE4 - leukotrienes; PHAT - platelet activating factor. Figure 2 - scheme of the metabolism of arachidonic acid, the red cross indicates the location of the action in this chain of metabolism nonselective blocker is clooxygenase lornoksikama. Figure 3 shows macular hole stage 2 with posterior vitreous detachment, figure 4 shows the successful result of surgical treatment of macular holes, figure 5 - a cyst in the macular region, figure 6 - the recurrence of macular holes with cystic swelling of the edges of the retina and increased retinal thickness, 7 - decrease swelling of the neuroepithelium after one week of use drops lornoksikama, Fig shows almost complete disappearance remained a small detachment of the neuroepithelium, do not influence significantly on visual function) swelling of the neuroepithelium of the retina and the closure of the macular hole after three weeks of using the drug.

Position 1 is the retin-a, item 2 macular hole, position 3 - the vitreous body, the position of the 4 - cyst macular area, position 5 - detachment of the neuroepithelium.

Clinical example

72-year-old man came to the clinic with complaints of decreased vision in the right eye (OD), the distortion of objects, loss of Central visual field. In history there were no injuries or intraocular inflammation. When optical coherence tomography (OCT), the study found macular hole stage 2 and partial vitreous detachment (figure 3). Vis OD=0,6 (ex). Did Subtotal vitrectomy with removal of VPM. Through the month again made OS is the study which showed excellent anatomic result of the operation of the macular hole was closed (figure 4). The patient's vision has improved. Vis OD=0,9.

However, six months later the patient complained of moderate vision loss, distortion lines. Vis OD=0,7. On OCT discovered a cyst in the macular region (lamellar hole) (figure 5). It was decided to dynamic monitoring of the clinical condition of the retina. Even after 2 months was diagnosed with macular hole (stage 4 (diameter 176 μm, at the base up to 820 µm) with cystic swelling of the edges of the holes of the retina and increased retinal thickness (6). Vis OD=0,3. After analyzing the situation, decided to assign the patient to lornoxicam in drops. After a week of use drops was noted positive dynamics: swelling of the neuroepithelium of the retina decreased, significant functional changes of view without (Fig.7). After another 2 weeks of using lornoksikama achieved almost complete disappearance of edema of the neuroepithelium of the retina and the closure of the macular hole (Fig). In the foveolar region was observed only small local retinal detachment, but it virtually disappeared after 3 weeks, during which the patient would not accept drops. Vis OD=0,9.

Within five months of monitoring the patient's condition remains stable is enim.

A method of treating operated metacrawlers macular holes, including the use of nonsteroidal anti-inflammatory drugs (NSAIDs), characterized in that as NSAIDs use 60% solution lornoksikama which is buried in the operated eye, 1 drop 4 times a day, for three weeks.



 

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2 dwg, 1 ex

FIELD: medicine.

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Eye drops // 2453304

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3 ex

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1 ex

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32 cl, 501 ex, 21 tbl

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25 cl, 2 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula I

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6 cl, 2 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new thiophene derivatives of formula (I) where A is represented by *-CO-CH2CH2-, *-CO-CH=CH, where the asterisks indicate the link through which the formula (I) thiophene group is bound; R1 is represented by C2-5alkyl; R2 is represented by hydrogen, methyl or ethyl; R3 is represented by hydrogen; R4 is represented by C1-4alkyl; R5 is represented by a hydroxy group, 2,3-di-hydroxypropoxygroup or -OCH2-CH(OH)-CH2-NHCOR52; R52 is represented by hydroxymethyl, and R6 is represented by C1-4alkyl; and to its salt. The invention also refers to the pharmaceutical composition that is agonistic in relation to S1P1/EDG1 receptor on the basis of the mentioned compounds.

EFFECT: new compounds and a composition based on them that may find their application in medicine as immunomodulating agents.

17 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of the formula (I) that are characterized by the properties of M3 muscarine receptor antagonist that is applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases. In the formula (I) A is represented by the oxygen atom or the group -N(R12)-; (i) R1 is represented by C1-C6-alkyl or the hydrogen atom; and R2 is represented by the hydrogen atom or the group -R5, -Z-Y-R5, -Z-NR9R10, -Z-NR9CO-R5 or -Z-CO2H; and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; or (ii) R1 and R2 together with nitrogen to which they are bound form heterocycloalkyl ring; the mentioned ring is displaced by the group -Y-R5 or -Z-Y-R5, and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; R4 is represented by the formula group (a), (b), (c) or (d); Z is represented by C1-C16-alkylene group; Y is represented by the link or the oxygen atom; R5 is represented by C1-C6-alkyl, aryl, phenyl condensed with C3-C6cycloalkyl, phenyl condensed with heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, C3-C6cycloalkyl or heteroC3-C6cycloalkyl group; R6 is represented by C1-C6-alkyl or the hydrogen atom; n and m equal 0; R8a and R8b are independently chosen from the group consisting of aryl, phenyl condensed with heterocycloalkyl, heteroaryl, C1-C6-alkyl, C3-C6cycloalkyl; R8c is represented by -OH or C1-C6-alkyl; R9 and R10 are represented independently by the hydrogen atom, C1-C6-alkyl, aryl, phenyl condensed with heterocycloalkyl and other components mentioned in the invention formula.

EFFECT: new compounds applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases.

10 cl, 49 ex

FIELD: chemistry.

SUBSTANCE: invention relates to thiophene derivatives of formula (I) where A denotes *-CO-CN=CH-, *-CO-CH2CH2-, or where the sign * indicates the thiophene bonding site in formula (I), R1 denotes hydrogen or methyl, R2 denotes n-propyl or isobutyl, R3 denotes hydrogen, methyl, ethyl, n-propyl, isopropyl or isobutyl, R4 denotes hydrogen or methoxy, R5 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy or hydrogen, R6 denotes -(CH2)k-(CHR65)p-CHR66-CONR61R62 hydroxy, hydroxy(C2-C4)alkoxy, di(hydroxy(C1-C4)alkyl)(C1-C4)alkoxy, 2,3-dihydroxypropoxy, -OCH2-(CH2)m-NHCOR64, -OCH2-CH(OH)-CH2-NR61R62, -OCH2- CH(OH)-CH2-NHCOR64 or -OCH2-CH(OH)-CH2-NHSO2R63, R61 denotes hydrogen, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethylethyl, carboxymethyl or C1-C4alkylcarboxymethyl, R62 denotes hydrogen, R63 denotes methyl or ethyl, R64 denotes hydroxymethyl, methyl aminomethyl or 2-methyl aminoethyl, R65 denotes hydrogen, R66 denotes hydrogen, m equals 1 or 2, k equals 0, p equals 1, R67 denotes hydrogen, C1-C4alkyl or halogen, and to a salt thereof. The invention also relates to a pharmaceutical composition for preventing or treating diseases or disorders associated with an activated immune system based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as immunodepressants.

31 cl, 2 tbl, 114 ex

FIELD: chemistry.

SUBSTANCE: compound is a matrix metalloproteinase or aggrecanase. The invention also relates to a pharmaceutical composition based on said compounds and a method of treating osteoarthritis, (I), where W is -C(O)-; R1 is bisphenyl, possibly containing one or more substitutes R5 and R6; and if R1 contains one or more substitutes R5 and R6, the substitutes can be identical or different; R2 is hydrogen; R3 is -CO2H, -CONHOH, -CONHR7 or -COOR7; R4 is -CONR9R10; m equals 0. The values of substitutes R5-R7, R9, R10 are as described in the claim.

EFFECT: compounds have the capacity to modulate metalloproteinase activity.

18 cl, 40 ex, 18 dwg, 6 tbl

FIELD: physics.

SUBSTANCE: design of contact lenses which are useful for preventing myopia and avoid discomfort when corneal shape changes, as well as undesirable side effects during medication, which is ensured owing to that the lens, according to one of its versions, has an optical zone comprising a central zone having an essentially constant distant vision focal power, a first circular zone which is concentric with the central zone and has positive longitudinal spherical aberration, and a second circular zone which is concentric with the first circular zone.

EFFECT: preventing development of myopia.

16 cl, 2 dwg

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