The selective drug action and the method of treatment of osteoarthritis

 

Combined preparation for the treatment of osteoarthritis of ximatron contains in each dosage unit, mg: as active principles - Ximena 20-30, prednisolone 2.0 to 3.0, as fillers (starch 4-5, talc 0.1 to 0.2. A method of treatment of osteoarthritis includes the introduction of therapeutic doses of ximatron orally 4-6 times a day for 4-5 days, then 1-2 times a day duration of treatment for 2-3 weeks and repeatability of courses from one to three with an interval of 20-30 days between courses. The new combined product expands the Arsenal of available therapeutic agents, can reduce the incidence of complications and side effects while maintaining high treatment efficiency. 2 C. p. F.-ly, 3 tables.

The invention relates to medicine, in particular to pharmacological agents and to a method of treatment of joints of the Centuries-long medical experience shows that virtually every man occasionally pain in the back and joints of the limbs (Nordemar R. back Pain. - M.: Medicine, 1988 - 144). Common rheumatoid arthritis is the most severe form of inflammatory joint disease is 3%, and non-inflammatory (degenerative) changes (which I for the treatment of articular diseases using various medications (urdan, aspirin, reapiring diclofenac, aspirin, antibiotics and others) who are ineffective. There are more than 100 non-specific pharmacological tools for the treatment of diseases of the joints, but it is too early to speak about drug inflation, as this problem is far from resolved due to lack of therapeutic effectiveness, neudovletvorennosti distant consequences.

In recent years, encouraging results were obtained from treatments with hormones and hormonal preparations made for the prototype (Vohralik B., Hormones and hormonal drugs in the clinic of internal diseases M. : Medicine, 1974. - 200 C.). By means of treatment in which drugs are used glucocorticoids, it is possible to slow down exudative processes of various origins (granulomatous, infectious) in inflammatory lesions of bone and joints, to reduce the treatment time and reduce the incidence of complications (ankylosis, contractures).

In acute traumatic aseptic processes or proceeding torpidly inflammatory diseases of the joints and paraartikulyarnye lesions (synovitis, bursitis, epicondylitis, tendovaginitis, periarthritis and others) obtained good effect from enterline.N. Corticosteroids in the treatment of surgical inflammatory disease. - M.: Medicine, 1968. - 132 C.).

The disadvantage of this method of treatment by intra-articular injection is the trauma, difficulty of implementation in the outpatient setting and most importantly the development of such severe complications as abscesses, septic arthritis and bursitis, paraartikulyarnye phlegmon and so on intra-Articular injections of hydrocortisone can cause damage to nearby blood vessels and nerves, so many doctors, including surgeons prefer treatment with oral use of hormonal therapy, especially when multiple lesions of joints (polyarthritis).

There is a method of treatment of non-specific diseases of the osteoarticular system prednisolone per se inside at a dose of 30-40 mg daily for 8-12 days with the transition to a maintenance dose (5-10 mg / day) (Hilariou I.e., Grishin, I. N. Corticosteroids in the treatment of surgical inflammatory diseases. - M.: Medicine, 1968. - 132 C.). Prednisolone is also used in the form of Priscila: prednisolone - 0.75 mg chloroquine phosphate 40 mg acetylsalicylic acid, 0.2 mg (per tablet) orally 2 tablets 3 times a day until a therapeutic effect within 1-2 weeks to let Hungary, reasaon, packaged in tablets containing 0.02 g (2 mg) of prednisolone and 0.15 mg butadiona and conventional fillers, such as talc, etc. In the treatment of them in the days designated to 6 tablets. This combination of mutually enhances the action of both components (Vohralik Century, Hormones and hormonal drugs in the clinic of internal diseases. -M.: Medicine, 1974. - 200 C.).

Along with non-specific anti-inflammatory action with short courses of treatment, the prototype has a number of significant drawbacks (Vohralik B., Hormones and hormonal drugs in the clinic of internal diseases. - M.: Medicine, 1974. - 200 C.): bright synergism of the components of the drug - Priscila (joint prednisolone with salicylates) dramatically increases its ulcerogenic side effect, which in most cases is manifested by severe pain, heartburn and epigastric and failure patients taking the medicine. In the 0.1-0.2% of cases, the formation of acute peptic ulcers of the stomach, which in some cases are formed even after two or three days of treatment, as confirmed by literature data (Ant I. A., Kozmin C. D., Kudrin A. N. The incompatibility of drugs. -M.: Medicine, 1978. - 240 S.); - the Genesis of gastric ulcers-the slots and increased pepsinoobrazoutei, as confirmed by our observations; - at the same time, the simultaneous use of prednisolone with butadiene (reasaon) causes antagonism, significantly reducing the activity of glucocorticosteroids, weakening their anti-inflammatory effect (Ant I. A. Kozmin C. D. Kudrin A. N. Incompatibility of drugs. M.: Medicine, 1978. - 240 C.); along with a pronounced anti-inflammatory effect not only is the restoration of damaged bone and cartilage tissue, and may even exacerbate the destructive processes, especially in cases intrasynovial the introduction of hormonal means in the form of suspension; - reduced the gap between therapeutic dose and the dose causing noticeable side effects; - corticosteroids as per se, and in this combination with chloroquine phosphate and acetylsalicylic acid), exerting a positive, antiphlogistine, desensitizing and protivoallergicheskoe action also possess immunosuppressive activity, which limits their use in introducing diseases; - the possibility of ulceration of the digestive tract, Genesis hemorrhagic pancreatitis, hyperglycemia, osteoporosis, increased blood coagulation, leukopenia (5) dramatically reduces the indications of permanent monitoring of the course of treatment; - reduced levels of prednisolone in the combined drug reduces therapeutic effect, causing the need to increase its daily dose, thereby increasing the risk of complications (inside 2 tablets 3-4 times a day);
notes instability long-term results, relapse of disease occurs in 40-60% of cases with short-term remission from 2 to 3 months.

In the end, it is necessary to emphasize, along with a high therapeutic effect in hormonal therapy possible Genesis of numerous complications that gravity is often more vyrazennie and more dangerous than the actual underlying disease, about which was used corticosteroid.

It is known as a therapeutic agent for inflammatory diseases (osteomyelitis and other) application of Ximena - (N(1--oxyethyl-4,6-dimethyl-1,2-dihydro-2 oxopyrimidine). Ksimedon approved by the pharmacological Committee of Ministry of health of the USSR from 26.12.1986, Protocol 22, and recommended for clinical use as burns of the drug and its industrial production in the pharmaceutical form tablets of 0.25, the Ministry of health 287 from 07.12.1993 was included in the state Register of medicines, retrasado food (RF Patent 2073514, MCI AND 61 TO 37/71. A method of treating patients with chronic osteomyelitis (in. A. Tereshchenko, E. N. Gabbasov, G. A. Izmailov and other Publ. 20.02.97// Invention. - 1997. - 5).

This drug has anabolic and anti-catabolic activity, stimulates cellular and immoral protective factors, i.e. provides the strengthening of protective forces of an organism to infection and does not provide a noticeable anti-inflammatory activity in chronic rheumatic processes (arthritis, spondylitis, osteoarthritis, muscular rheumatism) and aseptic inflammation of musculoskeletal system (gouty arthritis, arthrosis, arthritis, and others). There is evidence on the effectiveness of Ximena when gastric ulcer and duodenal ulcer and chronic gastritis (Ksimedon / Ed. by G. L. Izmailov. Kazan: IOPC them. A. E. Arbuzov, 1986. - 114 S.).

The aim of the invention is a new combination drug - ximation for the treatment of osteoarthritis, expanding Arsenal of available therapeutic agents that prevent the development of complications and side effects that increase the effectiveness of the treatment, expanding the indications for use and the method of treatment of osteoarthritis.

The aim is achieved by a combination drug containing in its composition it and prednisolone, and as a pharmacological excipient is starch and talc in the following ratio of components in each dosing unit dose, mg:
Ksimedon - 20-30
Prednisolone - 2,0-3,0
Starch - 4,0-5,0
Talc - 0,1-0,2
Drug dose in the form of tablets or powder made by mixing the components.

A method of treating osteoarthritis, which consists in receiving ximatron in the form of powder or tablets orally 4 to 6 times a day for 4-5 days to reach the first therapeutic effect, and then 1-2 tablets or powder per day with a duration of 2-3 weeks and repeatability of the course from one to three with an interval of 15-20 days between courses and then, if necessary, once in 4-6 months. Both existing start ximation (the active steroid and pyrimidine derivative) are well absorbed orally ingredients, so we offer a combined preparation for 1-2 hours and reaches its maximum concentration in the plasma. Introduction the preparation of starch and talc filler is needed as a binder in the amount of: starch - 4-5 mg talc - 0.1 to 0.2 mg.

Ximatron relatively quickly excreted from the body. In accordance with pharmacological Svornosti body, protective ability of the mucosa of the gastrointestinal tract, physiological regeneration and repair of bone and cartilage tissue with preservation of anti-inflammatory, desensitizing and anti-allergic activity.

An original combination drug - ximation for oral administration, which has expressed a polyvalent action, and the treatment was applied in the treatment of 120 patients (20 women and 18 men aged 40 years and older) with diseases of the osteoarticular system for various locations of the inflammatory process (table.1).

Almost all patients before treatment had previously received conventional treatment: nonsteroidal and steroidal anti-inflammatory drugs, physiotherapy, massage, stay in the sanatorium, intra - and paraartikulyarnye novocaine-hormonal blockade. The effect of these events was temporary. Stages of the disease ranged from two to thirty years. In only six cases, it was noted the relationship of the inflammatory process from the injury, the rest of the patients the cause of the disease was unknown.

The majority of patients we were treated on an outpatient basis. The control group consisted of 46 patients with similar disease treated is some examination of patients before and after treatment, including the required x-ray examination of the joints, reovasographiya limbs, biochemical tests (uric acid, sugar, sialic acids, C-reactive protein, rheumatoid factor, total protein and its fractions). As a rule (47), lesions of the joints was of the multiple - patients, except the injury complained of pain of varying intensity in many joints, with an emphasis on one of them. The criterion of effectiveness of the treatment also served as relief of pain in the affected area, restoration of function, the disappearance or reduction of inflammatory reactions: the reduction of swelling and skin redness, normalization of General and local body temperature. Special attention was paid to identifying the possible side effects with the subsequent occurrence of severe complications, durability of results, the duration of periods of remission and frequency of relapse.

The method of treatment was as follows. Patients recommended relative physiological rest with the restriction of the walk, the exception of heavy lifting, tight bandaging of the joint. In the absence of contraindications in the complex of therapeutic measures included taking ximatron on prideless, this produced a thick needle puncture, evacuated exudate, the cavity was rinsed with furatsilina with the subsequent introduction of antibiotics. The puncture was repeated.

Already 4-5 days patients showed a significant improvement in General condition, normalization of sleep and appetite, increase of motor activity. It was observed a complete disappearance of (60) or the weakening of local pain with a parallel increase in painless active and passive movements in the affected region. 6-8 day fell swelling, hyperemia and body temperature. By the end of the 2nd week 90% of patients almost believed himself to be healthy, although they have remained some of the signs of deformation, moderate swelling) of the disease. Faster priostanovlenie inflammation reverse the pathological process occurred in individuals with acute inflammation (steroidic), esteit, kondili, synovitis, and others). Slightly worse results of treatment of patients with deforming arthrosis with reactive secondary buritama, though they had but a little later (by the end of the 3rd week), was achieved regression of nonspecific inflammation in the tissues adjacent to astrochicken bone and saline formations. For illustration given m ilitary pains in the knee joints. Sick about 10 years. Repeatedly regarding joint diseases were cured permanently and health. Of comorbidities notes diabetes mellitus type II General condition is satisfactory. The heart rate of 78 beats per minute, rhythmic, BP 160/90 mm RT.article Muffled heart sounds. The body temperature of 37.8oC. Knee swollen joints, sharp pain on the right. The patella ballotine. 112 g/l, er. 5,21012l L 10109l, erythrocyte sedimentation rate of 30 mm/g; total protein 70 g sugar 5.5 mmol/l, uric acid 56 mg/l Produced the puncture of the right knee joint obtained turbid exudate (120 ml) followed by the introduction of 500 000 IU of penicillin. Appointed integrated traditional therapy and inside ximatron recipe: ksimedon 25 mg, prednisolone 2.5 mg, starch - 4,85 mg, talc - 0.15 mg on the proposed scheme. On the 4th day repeated puncture, which received about 5 ml transparent content. The patient's condition gradually improved, on the 19th day perifocal inflammation are gone. Discharged home in good condition. Viewed through the month, says pain after walking, swelling. A second course of treatment ximatron in the outpatient setting, after which the patient is of pokazateli during the course of treatment ximatron. Any side effects of the drug is not registered.

The results of the study drug, when appointing persons with concomitant diseases of the gastrointestinal tract (chronic gastritis, colitis and other), hypertension stage I-II and vegetative-vascular dystonia, diabetes portability ximatron was good. The data obtained indicate normalizing effect on many hematological indices, the functions of the vital organs, as well as lower the overall resistance of the organism.

Less therapeutic effect of ximatron was manifested in the decrease of Ximena (up to 20 mg and below) and prednisolone (up to 2 mg and below).

So, the patient I., 57 years old, came to the clinic 03.04.1998, complaining of severe pain in the joints, mostly in the left hip and knee. Last deformed, swollen, movement therein limited and sharply painful. Periodically conducted common inpatient and outpatient treatment. X-ray signs of Cox - and gonarthrosis. Initiated comprehensive treatment receiving ximatron with reduced content of ingredients below the lower boundary concentrations. When this is detected Neuchatel is via 2.5 weeks assigned ximatron with high dose ingredients: (ksimedon - 2 mg, prednisolone 2.5 mg), which immediately gave a positive clinical effect.

At the same time, though paradoxically, the increase in the content of active ingredients (Ximena more to 30.0 mg, prednisolone to 3.0 mg) combined drug - ximation did not lead to pharmacological its intensity and not identified advantages over the proposed content. Moreover, patients who took the drug with a high content of ingredients, often (50%) were found to have pronounced adverse events are identical and characteristic treatment of the prototype. The most frequent side effect was the development of dyspeptic symptoms. Here is one example.

Sick,, 48 years old, came to the clinic 10.01.2000, with complaints of pain in the right shoulder and elbow joints. With great difficulty changing because of the impossibility of lifting and lead hands. The pain intensifies in cold weather. Radiographically detected signs scapular-humeral periarthritis. Blood and urine were normal. Assigned therapy ximatron content Ximena 30 mg, prednisolone 3 mg on the proposed scheme. Showed a clinical improvement, but on the 4th day pain appeared in APHA is of ximatron continued at recommended dosage. There was a positive therapeutic effect without recurrent epigastric pain and heartburn.

The use of ximatron helped significantly reduce the incidence of side effects while maintaining high treatment efficiency (table.2). The proposed drug is well tolerated. Of side effects in 7% of patients in 2-3 days of treatment was observed only gastric discomfort, without interrupting therapeutic course spontaneously stopped after 3-4 days. Drug-induced cytopenia was not observed in any case. Periods of remission in 70% of patients ximatron exceeded 1.5 years and over.

In most cases (33) in patients with early stage osteoarthritis deformans had significant positive dynamics. Completely disappeared or decreased sharply with typical clinical signs of the disease - they got rid of the crunch, blockade, sensation of stiffness in the joints, swelling, spasm regional muscles. On radiographs disappeared angularity of the bone contour, has a tendency to moderate the increase in the height of the joint space and reduce the marginal proliferations. In the late stage of disease with significant bone changes with the deformation of the body was the restoration of the participants is dkoi, ugly bone growth became less pronounced.

About high-efficiency of ximatron show positive hematological and biochemical changes.

The drug contributed to the normalization of hematological and biochemical blood parameters (table.3) the Sudden removal climatological therapy did not lead to the onset of an exacerbation or relapse of the disease, about which was held this treatment. When performing surgical procedures (7) the drug has no inhibitory effect on wound healing.

Comparative data of the clinical application of the prototype and ximatron convincingly demonstrated significant advantages of the suggested original drug with pronounced previously unknown pharmacological subtle directional properties of nonspecific anti-inflammatory and regenerative actions before prototype.

Combined preparation for oral administration, which has strong anti-inflammatory effect, accelerates the repair and regeneration of cartilage tissue:
the proposed pharmaceutical composition active components can improve therapeutic efficacy, giving it nrepeat has minimal side effects (see table. 2) without reducing immunopositive reaction of the body against infection;
- has no ulcerogenic capacity;
- it has no negative effect on hematological and hemodynamic and function of other vital organs,
- does not cause aggravation and exacerbation of concomitant diseases (generalization of tuberculosis and localized non-specific infection, and so on):
- allows you to achieve a more stable therapeutic immediate and remote results, extending the periods of remission and reducing the frequency of relapse in the disease osteoarthritis.

The use of ximatron possible both in mono-and combination therapy, including visionista and surgery.

So, the proposed combination drug is effective in the treatment of osteoarthritis reduces side effects of drugs and the frequency of severe complications. Allows to obtain a more stable good short-and long-term consequences. Received therapeutic effect was not obvious and is not the sum of the effects of the active components, which clearly demonstrated in clinical trials.

Ximatron can recommend the service of doses per day to achieve the first therapeutic effect, and then 1-2 therapeutic doses per day with duration of treatment is 2-3 weeks and repeatability of courses from one to three with an interval of 15-20 days between courses.


Claims

1. The drug is a selective action for the treatment of osteoarthritis, containing the active principle and pharmacological filler, characterized in that the active agent it contains N(1--oxyethyl-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine)-ksimedon and prednisolone, and as a pharmacological excipient is starch and talc in the following ratio of components in each dosing unit dose, mg:
Ksimedon - 20-30
Prednisolone - 2,0-3,0
Starch - 4-5
Talc - 0,1-0,2
2. A method of treating osteoarthritis, comprising the introduction into the body of medicines, characterized in that as a drug use therapeutic dose of the drug under item 1 oral 4 to 6 times a day for 4-5 days until the first therapeutic effect, and then 1-2 times per day with duration of treatment ranging from 2 to 3 weeks and repeatability of courses from one to three with an interval of 15-20 days between courses.

 

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