Non-steroid anti-inflammatory preparations are characterized by a stable trend to qualitative and quantitative extension. This is associated with a number of medical, social and economic reasons. The growth of the number of patients, mainly elder ones, suffering from arthritis of various etiology is explained by the rise of demand of these drugs. Non-steroid anti-inflammatory preparations (NAIP) firmly occupy third place (after antibiotics and cardiovascular preparations) in the structure of use of separate groups of drugs in industrially developed countries [10]. It is worth noting that in addition to a wide range of NAIP over 1000 multicomponent drugs (tablets, capsules, candles, injections, ointments, gels) developed on their basis are used in medical practice [4, 5, 6]. Most active of contemporary NAIPs such as orthophen (sodium diclofenac), indometacin, naproxen, ibuprofen, pyroxynam and other preparations are widely used for treatment of rheumatic diseases The mechanism of action of existing NAIPs is not completely clear. It includes effect on various links of inflammatory process pathogenesis and is first of all associated with formation and action of so called inflammation mediators [1, 5, 12, 13, 16]. NAIPs change activity of some lysosomic ferments, damage redox processes in inflammation focus, retard cinegenesis, impact immune mechanisms and damage eicosanoids biosynthesis. This latter effect of NAIPs is considered as the most important of known acting mechanisms of this group of preparations [10, 11, 12]. Nowadays only a single way of regulation of the cascade of arachidonic acid, i.e. cyclooxygenase way, associated with retardation of formation of prostaglandin and prostaglandin 12, is learned in detail. The search of preparations retarding cyclooxygenase and lipooxygenase ways of arachidonic acid metabolism is one of directions in creation of new generation of NAIPs [1]. The study of substances activating prostaglandin biosynthesis or retarding eucosanoids is the other way for studies in this sphere. Among other contemporary routs of NAIPs creation production of analogs of known preparations, development of prodrugs and synthesis of compounds containing of molecules of know preparations, is worth noting. One of way to obtain higher efficiency and safety of NAIPs is the development of prodrugs, i.e. transforming into an active form after their administration in human body. Among such preparations sulindac is worth notice. Action of this preparation is much longer than that of indometacin and it gives much lesser complications in gastrointestinal tract. Also among new routes of NAIPs development we must note synthesis of compounds causing ND anti-inflammatory effect to acting mechanisms other than those associated with the impact on cascade of arachidonic acid. These are such preparations as proquason, fluproquason and emorfason. Emorfason is an active inhibitor of quinine-forming ferments (callicreins) and prevents formation of quinines, inflammation mediators [10, 12]. Diclofen-gel, made by Borschagovsky CPP, is a transdermal form of sodium diclofenac and shows anti-inflammatory and analgesic effects, conditioned by biosynthesis of prostoglandins, quinines and other inflammation and pain mediators, stabilizing effect on lysosomic membranes and reducing capillary permeability. Menthol, contained in this gel, intensifies an analgesic effect of sodium diclofenac. Diclofen-gel is applied on skin 2 to 4 times a day. The preparation must be applied on undamaged skin areas, avoiding getting into eyes and on mucous coats. Average daily dose is 4.0 g gel, which is equivalent to 120 mg sodium diclofenac. The use of gel may be combined with ingestion of sodium diclofenac tablets in maximal daily dose 50 mg. Generally, Diclofen-gel is well tolerable. However, in some patients local skin irritation, itching or hyperemia may occur. When diclofen-gel is applied on large skin areas or in case of overdosage, systematic side effects, peculiar for diclofenac and other non-steroid anti-inflammatory drugs, such as unpleasant feeling in epigastric region, dyspeptic phenomena, diarrhea, headache, vertigo, which requires preparation dose reduction. No pathologic interaction with other drugs with diclofen-gel use had been ascertained. Although diclofen-gel may be used in combination with diclofenac tablets, take into consideration that the latter may result in specific effects and ulcerogenic effect of corticosteroids, in rise of digoxin in blood and reduce action of diuretics. Its therapeutic efficiency when used with salicylates reduces, while ulcerogenic effect on mucous coat of the stomach is intensified. When diclofen-gel is used in combination with anticoagulants, the status of blood coagulation system must be monitored. Ukrainian rheumatological center used diclofen gel, a combined preparation for external use, based on highly effective pharmacological compound – sodium diclofenac. Voltaren emulgel, made by company “Siba-Gaygy” (Switzerland), anti-inflammation and analgesic preparation for external use, containing non-steroid preparation diclofenac, was selected as a reference preparation. Quantity of diclofenac resorbed through skin is proportional to the time of contact and area of application and depends on total preparation dose and on skin hydration rate. Upon applying emulgel on skin over hand and knee joints diclofenac is detected in blood plasma (its maximal concentration is less than after ingestion of Voltaren tablets). Due to water-gel basis and menthol content this preparation provides local analgesic and cooling effect. Materials and studying methods. Involved in the studies were 45 patients with osteoarthrosis (OA) of mainly hip and knee joints (2nd clinic roentgenological stage) and two patients with 3rd clinic roentgenological stage. The patients were divided into two groups: 1st group (30 patients) received diclofen-gel, made by SPC “Borschagovsky chemical and pharmaceutical plant” and a control group (2nd group consisting of 15 patients) received Voltaren emulgel, made by company “Siba-Gaygy” (Switzerland). Both groups were divided by sex, age and diseases stage. Patients of both groups received preparation sodium diclofenac in daily dose 50 mg. Preparation diclofen-gel was prescribed locally twice a day within 10 days. Preparation Voltaren was prescribed in a similar scheme. For studying joint status a “Joint Record” containing both objective and subjective data was used. Pain syndrome intensity (by visual decimal pain evaluation scale), pain, joint and inflammation indexes (in points) with the account of Lansbury factor, the use of which permits to obtain an objective evaluation depending on damaged joint size and its functional value, were studied. The pain index was evaluated by the scale of 0 to 3 points with active and passive movements in joints in order to define their painfulness. The joint index (0 to 3 point scale) was defined by joint palpation to ascertain joints painfulness and functional abilities. The inflammation index (0 to 3 point scale) was defined by joint examination and palpation to ascertain exudation (i.e. existence of synovitis). As subjective data complaints of patients, data of anamnesis, time of illness, rate of aggravation repletion, medicamental and other treatment types were considered. The efficiency of treatment was evaluated by 5-pint scale: general patient status – very well, OK, satisfactory, bad and very bad. In doing so, the fact that with failure of metabolic processes in joints their mobility is restricted due to deterioration of functional abilities and progressing degenerative and dystrophic changes in damage of damping properties, was considered. Special attention was paid to studying the efficiency of complex treatment of OA in patients at 3rd clinic and roentgenological stage. To obtain objective treatment results, they were evaluated by both physician and patient. Instrumental study methods included roentgenography of hip and knee joints. In laboratory tests total blood count, the level of urine aspartate aminotransferase, alanine aminotransferase and creatinine were defined. Results and their discussion. As a result of treatment with the use of diclofen-gel twice a day and of sodium diclofenac 50 mg a day an expressed improvement of the majority of patients was noted excluding 2 patients with 3rd clinic roentgenological stage of OA with expressed changes conditioned by degenerative and dystrophic processes. In these two patients the efficiency of treatment was evaluated as satisfactory, while in 28 patients with 2nd clinic roentgenological stage of OA it was valuated as OK and very good. Average intensity of pain syndrome in 1st group was 7.21 + 0.55 points before and 3.61 +0.57 points after treatment. In the control group a positive pain syndrome dynamics was evaluated as 7.81 +0.61 points before and 3.21 + 0.31 points after treatment (р<0,01). As initial intensity of pain feeling in the tested group was different a corresponding different reduction of this indicator was noted. In both groups practically identical indicators of pain feeling were noted. In both groups in whole and in individual patients an essential reduction of pain syndrome independent of initial pain syndrome intensity was confidently noted. A direct dependence of treatment efficiency on osteoarthrosis gravity was ascertained. In patients with 3rd clinic roentgenological stage of OA with an expressed restriction of joint functions, degenerative changes of cartilage and joint deformation a week positive dynamics of pain syndrome was noted. The reduction of pain syndrome intensity was conditioned by the reduction of concomitant inflammation gravity. A comparative analysis of pain syndrome distribution in patients of both groups a single directivity of dynamics was ascertained: practically there were no patients with negative dynamics of this indicator. Thus, we may state that the use of diclofen-gel resulted in confident and essential reduction of average values of pain syndrome both in the group as a whole and in individual patients. This makes it possible to recommend diclofen-gel for OA treatment, including as an analgesic. To obtain more objective treatment results, we have analyzed treatment results by 5-point scale both by physicians and patients independently. Physician’s evaluation equaled to 4.15 + 0.25 points (р<05), and patients’ evaluation - 4.03 + 0.18 points (р <0,05). Despite anonymity of evaluation of treatment efficiency by physicians and patients final pints were practically the same: patients’ and physician’s evaluations in 1st group coincided in 92.5% cases and in 2nd group – in 93.2% cases. These data prove the advisability of diclofen-gel use for patients with OA. The improvement of articulating, inflammatory and pain indexes, characterizing joint function in whole, was noted. Pain intensity with active and passive motions as well as with joint palpation significantly reduced. The reduction of articulating, inflammatory and pain indexes were conditioned by retardation of pathological process progress. Thus, course treatment of patients with OA using diclofen-gel resulted in an essential improvement of average value of articulating, inflammatory and pain indexes, which characterize joint function as a whole. Approximately equal values of articulating index were noted in both groups, which confidently reduced at the treatment end. The reduction of articulating index in the group of patients who received diclofen-gel corresponded to that in group of patients receiving Voltaren emulgel. The dynamics of inflammatory and pain syndromes in both groups was unidirectional. Dynamics of articulating, inflammatory and pain syndrome of preparation diclofen-gel corresponded to that of preparation Voltaren emulgel. As quantity of sodium diclofenac resorbed through skin is proportional to time of contact and to are, where it is applied, and depends on total preparation dose, we advised to apply an occlusive bandage for 8 to 10 hrs for 10 patients of the 1st group and 10 patients of 2nd group. The application of an occlusive bandage resulted in more expressed dynamics of pain syndrome, which fact is probably due to better resorption of sodium diclofenac. The hand power (HP) is an important indicator of functional status of peripheral hand joints with their lesion in patients with OA. We involved in the study patients with OA, mainly with lesion of hip and knee joints, however lesion of peripheral joints was noted in practically all patients. We have deeply analyzed the distribution of values under study in examined patients. In medical practice we used a dynamometer having a high resolution and maximal dial range 30 kg. We excluded patients whose initial HP values exceeded maximal dynamometer range from the analysis. With account of correction rise of HP of both right and left hands was noted in the majority of patients. This fact demonstrates that in line with reduction of pain syndrome preparation diclofen-gel improves blood circulation metabolic processes in the injured region and thus execution of works with greater loading. In two patients pain in epigastric region were noted. After explaining of the cycles of sodium diclofen use, appropriate diet and antacid pain in epigastric region disappeared (it must be noted, that two patients suffered from chronic gastritis). Neither side effects nor laboratory indicator changes were recorded in the process of diclofen-gel use. CONCLUSION Limited clinical studies of the use of combined preparation diclofen-gel in patients with osteoarthrosis a confident positive dynamics of pain syndrome was ascertained. It was demonstrated that the use of occlusive bandages results in a more expressed dynamics of pain syndrome, which fact is probably due to higher sodium diclofenac resorption. Confident reduction of inflammatory, pain and articulating indexes was noted, which fact evidence positive dynamics of joint components. Also, greater hand power in patients with osteoarthrosis with lesion of peripheral joints was shown. A direct dependence of treatment efficiency on the rate of gravity of osteoarthrosis and expressiveness of degenerative and dystrophic changes in joints was ascertained. No side effects in patients treated with preparation diclofen-gel were recorded. In the process of comparative trial tests an undoubted positive effect of the use of preparation diclofen-gel, made by SPC “Borschagovsky chemical and pharmaceutical plant”, which does not yield by all studied parameters to reference preparation Voltaren emulgel, produced by company “Siba-Gaygy” (Switzerland) was demonstrated.

LITERATURE

1. L.I. Benevolenskaya, M.M. Bzhezosvky “Epidemiology of rheumatic diseases”, Meditsina”, Moscow, 1988.
2. V.I. Kulikov, G.I. Muzya "Lipid derivatives of prostoglandins and of non-steriod anti-inflammatory drugs” (Review). Scientific-and-production center of medical biotechnology of Medical industry department of Ministry of public health of Russia, Moscow. Journal of chemistry and pharmaceutics, No. 4 1997.
3. V.A. Nosova, Ya. A. Sigidin "Pathogenic therapy of rheumatic diseases”. “Meditsina”, Moscow, 1985.
4. V.A. Nasonova, L.V. Yakovleva, G.N. Pleskovskaya et al. Thesises of report at II Russian congress “Humans and drugs”, Moscow, 1995, p. 120.
5. N.S. Nasybbulina "NAIPs and their dosage forms” (Review), p. 30-34.
6. Ya. A. Sigidin, G. Ya. Schwartz, A.P. Arzamastsev, S.S. Liberman "Medicinal therapy of inflammatory process”. Moscow, 1998.
7. T.D. Skalaban, L.I. Volkova, N.N. Alexeyeva, E.V. Yegorova "Non-steroid anti-inflammatory drugs” (Review). Information of Central information bureau of Ministry of medical industry. Chemical and pharmaceutical industry. Moscow, 1985, Issue No. 7.
8. F.P. Trinus "Pharmaceutical and therapeutic handbook”. “Zdorovie”, Kiev, 1987.
9. F.P. Trinus, B.M. Klrbanov, I.M. Gandja, R.D. Seyfulla "Pharmacological regulation of inflammation”, Kiev, 1987.
10. L.A. Chayka, Ya.U. Khodzhay, G.V. Obolentsova et. al. "Pharmaceutical Journal", Ukraine, No. 3, p. 34, 1990.
11. G. Ya. Schwartz "New ways in creation of anti-inflammatory preparations”, “Chemical and pharmaceutical journal”. 1998, No. 11, p. 1317-1326.
12. Drugs safety. Express information, No. 10, 1996.
13. P.B. Costello, A. N. Baer and F.A. Green "Inflammation", 15 269-279 (1991).
14.C.N. Hong "Drugs Future", 15, page 245-253 (1990).
15. K.J. Hostetler, L.M.Stuhmiller, H.B.M. Lenting et al, "J. Biol. Chem", 265, page 6112-6117, 1990.
16. M.Koltai, P.Guinot, D.Hosford et al "Adv. Pharmacol", 28, 81-167, (1994).
17. H.Van den Bosch, M.H.P. Van den Besselaar, "Adv Prostaglandin Thromb". Res., 3, 69-75, (1978).
18. W.F. Stenson and C.W.Parсer, "Prostаglanelins, 28, 285-292, 1979.