Tizol gel for external use 10g Olympus/Russia

Tizol ointment with aminophylline is prepared in industrial pharmacies. You can buy it with a prescription; instructions for use are included with the drug.

Eufillin is a synthetic drug based on theophylline and ethylenediamine, when used externally:

• has an anti-inflammatory effect;
• dilates blood vessels;
• activates blood circulation;
• relieves pain.

The introduction of the substance through electrophoresis provides an effect mainly in the skin and subcutaneous fatty tissue, and acts in the lesion for more than a day. Electrophoresis with aminophylline is widely used in pediatric neurology, traumatology and otolaryngology. The procedure effectively relieves bronchospasm, spasm of smooth and even striated muscles, activates diuresis, stimulates the heart and respiratory center, reduces intracranial pressure in children, and improves muscle tone. However, when performing electrophoresis, many side effects arise that narrow the possible field of application of this method: headache, insomnia, tremor, decreased blood pressure, hypoglycemia, heart rhythm disturbances, etc.

Strengthening the beneficial properties of aminophylline due to tizol

Tizol is a multifunctional gel. It has radioprotective, anti-inflammatory and reparative properties, and is able to associate with other pharmacological agents, including aminophylline, preserving their properties without change.

The tizol molecule, an associate of a titanium atom and a glycerol molecule, has high transcutaneous permeability, is capable of sorbing other medicinal molecules and transporting them under the skin and even deeper, working as a conductor and amplifier of their properties.

Using Tizol as a natural accelerator for aminophylline transport under the skin has many advantages:

• soft painless introduction;
• non-invasive;
• absence of negative adaptive reactions to the electric field;
• the ability to carry out treatment in a more comfortable home environment, which significantly reduces stress reactions in children.

Adverse reactions

It is worth noting that side effects during treatment with ointment are quite rare. It is only possible that a reaction to aminophylline may develop if the drug enters the gastrointestinal tract unintentionally:

• Signs of allergies
• Abnormal stool
• Nausea
• Change in heart rate
• Sharp decrease in blood pressure
• Tremor
• Deterioration of basic blood parameters.

Although the drug is prescribed to infants from 1 month. (as indicated in the instructions) and it rarely causes side symptoms, you should definitely consult a doctor before using the ointment. The treatment regimen can be prescribed individually.

Application area

Tizol-based ointment with the active substance aminophylline is widely used in neurology, urology, dermatology, traumatology, ENT practice and nephrology of infants and young children. The high penetration of this therapeutic complex into tissue is due to both the hydrophilicity of soft tissues and some immaturity of bone, which has a significant cartilaginous component. The ointment is used to solve problems of the joint and ligamentous apparatus, and to treat skin diseases with an inflammatory component. In nephrology, the complex with aminophylline is relevant in conjunction with the drugs tizol-heparin and tizol-proserin to stimulate kidney development in the neonatal period, in neurology - for the treatment of perinatal hypoxia.

All these methods developed as an alternative to electrophoresis; the obvious advantages of using the ointment externally suggest the further development of new promising methods on this basis.

Mode of application

An ointment, the components of which are tizol with aminophylline, is applied topically, externally. According to the instructions, a thin layer is applied to a previously cleaned area of ​​skin or joint surface 3 times a day. Do not rub in; wait until the ointment is completely absorbed (15–20 minutes). The duration of treatment is usually 10–15 days, depending on the doctor’s prescription. As part of complex therapy in pediatric nephrology - application of ointment to the neck and spine for 5-10 minutes, the course is also 10-15 days.

Materials/publications

R.M.
Balabanova, T.P. Fedina State University Institute of Rheumatology of the Russian Academy of Medical Sciences, Moscow
Purpose. To evaluate the effectiveness, tolerability and safety of 1% Tizol gel in monotherapy and in combination with diclofenac (0.5%) and hydrocortisone (0.05%) for rheumatoid arthritis (RA).

Material and methods. The study included 88 RA patients with exudate in the affected joints. Using the randomization method, patients were divided into 3 groups: Group I (3 persons) received local treatment with 1% Tizol gel, II - a complex preparation that included 1% Tizol, diclofenac (0.5%) and hydrocortisone (0.05%). Group III (28 people) was a control group and received a local 1% gel, the active ingredient of which was diclofenac (manufactured by Hiperion S.A., Romania). The drugs were applied in a thin layer to the entire surface of the inflamed joint three times a day for 14 days. The effect was assessed before and after the course of treatment by the severity of pain syndrome (VAS) in mm, the circumference of the joint under study and the degree of joint dysfunction (WOMAC index). Laboratory examination included complete blood count, liver enzyme levels and clinical urine analysis.

Results. Local therapy for RA contributed to a decrease in pain, the circumference of the assessed inflamed joint, an increase in range of motion and a decrease in the dose of NSAIDs. A good effect prevailed and was significantly significant in the first two groups of patients (53% and 60%, respectively). The local therapeutic effect of the drug in group I, according to patients, lasted an average of 2.5 hours. Local therapy was well tolerated in all patients, without systemic side effects.

Conclusions. 1% Tizol Gel and its combination with diclofenac (0.5%) + hydrocortisone (0.05%) are effective for local therapy of patients with RA, significantly reducing pain and inflammation in the affected joint. The drugs can be used in the treatment of inflammatory joint diseases, especially in patients with concomitant diseases of the gastrointestinal tract, arterial hypertension, as well as when it is impossible to take NSAIDs orally and/or the need to reduce their dose.

Key words: rheumatoid arthritis, local therapy, Tizol gel

The clinical picture of rheumatoid arthritis (RA) is manifested primarily by an inflammatory articular syndrome caused by synovitis and damage to periarticular tissues. Patients with RA require continuous therapy with non-steroidal anti-inflammatory drugs (NSAIDs), the mechanism of action of which is associated with the suppression of the activity of cyclooxygenase (COX) - a key enzyme in the metabolism of arachidonic acid - a precursor of prostaglandins (PG) - a mediator of pain and inflammation [1,2].

All “standard” drugs of this class have common positive and negative properties. The use of NSAIDs, even short-term and in small doses, is often limited due to the high risk of adverse reactions, having an adverse effect on the gastrointestinal tract (dyspepsia, erosion and ulcers of the mucous membrane, which may be complicated by bleeding), kidneys (delay sodium, increased blood pressure) [3]. At the same time, alternative routes of administration of NSAIDs (parenteral, rectal) do not protect patients from the possibility of developing gastroenterological and other side effects due to systemic action. Therefore, in recent years, special attention has been drawn to the problem of the safe use of NSAIDs. The use of new generation drugs—selective COX-2 inhibitors, with a lower potential for side effects, has not allowed us to finally solve the problem of the safety of therapy [4]. NSAIDs used locally in the form of ointments, creams and gels have a certain effectiveness and lack of general toxicity. Local application of drugs has virtually no contraindications and is acceptable at any age, regardless of the presence of concomitant diseases, being a significant addition to the systemic prescription of NSAIDs. In some cases, local NSAIDs can reduce the dose of the oral form of the latter. Favorable results are obtained by applying a local agent 3-4 times during the day in an optimal therapeutic dose, taking into account the severity of the inflammatory process, the size of the affected joint and the condition of the skin [5].

One of the drugs for local therapy of arthritis is Tizol gel, developed by Ural scientists and produced by OLIMP LLC (Ekaterinburg). The drug is approved by the Ministry of Health of the Russian Federation for medical use as an anti-inflammatory agent for local use [6].

Tizol gel is an aquatic complex of titanium glycerosolvate. As a metal complex compound, it has anti-inflammatory and bactericidal effects. Titanium, which is part of Tizol, is necessary for the construction of epithelial tissue, the formation of callus, and the maintenance of the processes of immunogenesis and erythropoiesis. Tizol combines well with many pharmacological drugs, which facilitates their transportation to the pathological site. The drug has a prolonged effect, the ability to stimulate tissue regeneration, and is non-toxic [7,8].

The purpose of this work was a comparative assessment of the effectiveness, tolerability and safety of Tizol gel, its combination with diclofenac (0.5%) and hydrocortisone (0.05%) when applied locally in patients with RA.

Material and methods

The study included 88 RA patients (74 women and 14 men) with clinical signs of active arthritis. The duration of the disease ranged from 0.5 to 33 years (average 9.5+7.4 years), the average age of the patients was 48.9±15.7 years. The patients were divided into three groups. Patients of group I (ZO persons) applied 1% Tizol gel in a thin layer to the area of ​​the inflamed joint three times a day. For group II (ZO persons), a gel was used in which the active ingredients were Tizol (1%), diclofenac (0.5%) and hydrocortisone (0.05%). In group III (28 people), 1% diclofenac gel was used (Hyperion S.A., Romania). During the entire treatment period (14 days), no other local therapy (medicinal, including intra-articular, and physiotherapeutic) was carried out. Systemic NSAID therapy did not change during the entire study period, as did the basic therapy, which 67 patients received: methotrexate (23), sulfasalazine (13), azathioprine (10), leflunomide (5), plaquenil (16) in therapeutic doses. A third of the patients were on a maintenance dose of prednisolone no more than 10 mg/day. Patients were examined before the start of treatment and after completion of the course of local therapy, the effect of which was assessed by the severity of pain (VAS, mm), degree of impairment of motor function (WOMAC, mm), circumference of the _______affected joint in cm. The effect of therapy was also assessed according to the patient’s opinion (good , satisfactory, no effect), time of onset of effect and duration of action of the drug after applying the gel to the skin of the inflamed joint and the presence of side effects. Monitoring of general and biochemical blood tests, general urine analysis made it possible to assess the safety of treatment.

Statistical processing was carried out using the methods of variational medical statistics (Statistica program, version 5) using Wilcoxon tests, when comparing groups - Mann-Winty, x-square and Cruz-Cala-Wallis tests.

results

All patients completed the 2-week study. In group I of patients treated with 1% Tizol gel, there was a significant improvement in all studied clinical parameters: severity of pain according to VAS, WOMAC index, volume of the inflamed joint (Table 1).

Table 1

DYNAMICS OF CLINICAL PARAMETERS IN RA PATIENTS DURING LOCAL THERAPY WITH 1% TIZOL GEL

The duration of the local therapeutic effect of Tizol after application to the skin of the joint, according to the patients, was 131±76 minutes (from 20 to 360 minutes). A good effect occurred in 16 (53%) patients, a satisfactory effect in 8 (27%), and no effect in 6 (20%). Tolerability of the drug was excellent in all cases.

In group II of patients, a combination of Tizol with diclofenac (0.05%) and hydrocortisone (0.05%) was used topically. There was also a significant decrease in the severity of pain syndrome (VAS), WOMAC index and volume of the joint under study (Table 2).

table 2

DYNAMICS OF CLINICAL PARAMETERS OF RA PATIENTS ON THE BACKGROUND OF LOCAL THERAPY OF COMBINATION AND TIZOL WITH DICLOFENAC AND HYDROCORTISONE

Table 3

DYNAMICS OF CLINICAL AND LABORATORY PARAMETERS IN RA PATIENTS DURING LOCAL THERAPY WITH 1% DICLOFENAC GEL

A good effect was observed in 18 (60%) patients, a satisfactory effect in 10 (33%), and no effect in 2 (7%) patients. No adverse reactions were identified. In the group of patients who used diclofenac gel (group III), the severity of pain according to VAS and the volume of inflamed joints significantly decreased (Table 3). The drug was effective in 26 patients (93%), but a good effect was noted only in 4 (14%) cases, in 22 (79%) it was satisfactory, and in 7% local treatment was ineffective. There were also no adverse reactions in this group of patients. A comparative assessment of the effectiveness of various types of treatment is presented in table. 4. In group I, therapy was effective in 80% of cases, in groups II and III - in 93% of patients (p <0.05). However, in the diclofenac group the effect was predominantly (in 79% of cases) satisfactory, while in groups I and II a good effect prevailed. The effect of local therapy on the severity of pain according to VAS and joint function (WOMAC index) was comparable in groups I and II. The volume of inflamed joints significantly decreased in all groups, and the severity of the effect did not differ between groups (p = 0.7). The effect of Tizol lasted for an average of 2.5 hours after application to the skin. The duration of action of Tizol in combination with diclofenac and hydrocortisone was on average 3.5 hours, diclofenac gel - 2 hours. During treatment, in 4 patients of group I, in 6 patients of group II and in one patient from group III, it was possible to reduce the daily dose of NSAIDs by 25-50% (Table 5). According to patients, the effectiveness of Tizol was comparable to the effect of fastum gel (Ppatients), dollit cream, (7), voltaren gel (15), and Nise gel (13), previously used by patients. The effectiveness of the combination of Tizol with diclofenac and hydrocortisone was similar (17), and in some cases, was superior, according to patients, to the effect of Dollit cream (10), indomethacin ointment (10), and Voltaren gel (8).

Tolerability of all three types of local therapy was assessed as good. No side effects were identified during treatment. There was no effect of the drugs on the levels of hemoglobin, leukocytes, eosinophils, or transaminases in the blood serum. There were no changes in clinical urine analysis during treatment.

Thus, our results showed that 1% Tizol gel is an effective drug with analgesic and anti-inflammatory effects in local therapy of RA.

Table 4

EFFECTIVENESS OF DIFFERENT TYPES OF LOCAL THERAPY IN RA PATIENTS BY GROUPS

Table 5

COMPARATIVE ASSESSMENT OF THE EFFECTIVENESS AND TOLERABILITY OF DIFFERENT TYPES OF LOCAL THERAPY IN RA PATIENTS

During 14 days of treatment, a significant decrease in pain, volume of inflamed joints and an increase in motor function was noted, which helped reduce the daily dose of NSAIDs by 25-50% and improve the quality of life of patients. When comparing the effectiveness across groups, a good and satisfactory effect was found in 24 (80%) patients using 1% Tizol gel, and in 28 (93%) Tizol in combination with diclofenac (0.5%) and hydrocortisone (0.05%) , whereas in the group where only 1% diclofenac was used topically, the effect was mostly satisfactory in 22 (79% of patients). The drugs were equally well tolerated. Preparations containing Tizol were not inferior in effectiveness to Dollit cream, indomethacin ointment, and Nise gel. This study confirmed the therapeutic activity of 1% Tizol gel and its effectiveness in local treatment of inflamed joints in patients with RA both in inpatient and outpatient settings.

LITERATURE

1. Nasonov E.L., Nasonova V.A. Pharmacotherapy of pain: the view of a rheumatologist. Consilium medicum, 2000, 2, 12, 509-513.

2. Nasonov E.L. Anti-inflammatory therapy of rheumatic diseases. M., RMZh, 1996, 22, 1023-1025.

3. Nasonov E.L., Karateev A.E. Gastric lesions associated with non-steroidal anti-inflammatory drugs. Klin, med., 2000, 3, 4-9.

4. Nasonov E.L. Non-steroidal anti-inflammatory drugs (prospects for use in medicine). M., 2000, 262 p.

5. Chichasova N.V. Local use of analgesics for diseases of the joints and spine. Consilium medicum, 2001, 3, 5,215-217.

6. State register of medicines of the Ministry of Health of the Russian Federation. Pharmacopoeial article M., 2000, 42-3417-97.

7. Sokolova L.A. Reactive and rheumatoid arthritis: the triggering role of the infectious factor and new approaches to diagnosis, assessment of severity and treatment. Auto-ref. diss. Doctor of Medical Sciences Yaroslavl, 2002.

8. Sokolova L.A. Tizol and its use in local therapy of rheumatoid arthritis. Scientific and practical rev-matol., 2002, 3, 39-41.