A means for local antirheumatic therapy


(57) Abstract:

The invention relates to medicine, in particular to the means for local Antirheumatic therapy. The invention lies in the fact that we offer the following composition comprising dimethylsulfoxide, oxybutyrate lithium or sodium, a local anesthetic, an antihistamine, gelatin and water. The invention provides a rapid analgesic effect. In addition, local anesthetics possess the property of inhibitors of phospholipases, making a positive effect on the processes of free-radical oxidation of lipids and partially to prevent possible allergic reactions, also potentiate the analgesic and anti-inflammatory effects of the proposed tools.

The invention relates to medicine, namely to rheumatology, in particular to expand the range of local Antirheumatic therapy on the basis of the pathogenetic approach to the treatment of inflammation of the articular and periarticular tissues.

Mild synovitis and periarthritis when astrologicheskih diseases is relevant not only from a tactical point of view (reduction of pain and stiffness in affected joints), but it is strategically important, as the development process and leads ultimately to a significant restriction of functional ability of joints.

Currently known means local anti-inflammatory therapy: ointments, elementy and gels containing as the active active ingredient steroidal anti-inflammatory drug. As bases and carriers in a variety of compositions containing both hydrophilic and hydrophobic agents: glycols, propylene glycols, polyethylene oxides, cellulose ethers, lanolin, vaseline. Meanwhile, the influence of ointment bases are not indifferent to the body. Thus, the presence of the toxic effect of the ointment on the basis of sodium-carboxymethylcellulose and proposed the use of collagen for the preparation of ointments with local anesthetic substance (as the USSR 833241, class a 61 K 9/06). However, the technology of preparation of this ointment bases requires grinding of collagen in a ball mill with liquid nitrogen cooling to-150-190oC, which requires special equipment.

Regardless of the root cause that caused the inflammation, maintaining a large role disturbances of microcirculation and synovial hypoxia environment and periarticular structures. Metabolic changes associated with hypoxia, include a decrease in the rate of electron transport in the respiratory chain, separation ocil the biological membranes. In this regard, rational use of local therapy not only steroid and nonsteroidal anti-inflammatory drugs, but antihypoxants, antioxidants.

Among the substances which are widely used in local Antirheumatic therapy, antioxidant activity has sulfoxide (Bilenko, M. C. Ischemic and reperfusion injury of organs, M, 1989, S. 305).

It is also known application of dimethyl sulfoxide funds for local therapy not only as anti-inflammatory and analgesic activity, but also as an agent that improves penetration into tissues other drugs (as the USSR 1196001, the patents of the Russian Federation 2014070, 2027432, class a 61 K 9/06).

On the application of dimethyl sulfoxide based achievement anti-inflammatory and chondroprotective effects in the means for local use (RF patents 2021811, 2085194, class a 61 K 31/73). These funds contain chondroitin sulfate or fractions polysulphate, which transdermal penetration directly to the periarticular and synovial tissues at the expense of dimethylsulfoxide. Specified in these tools, lanolin, vaseline base is inert in the relationship significantly more expensive.

Known also enable Dimexidum in compositions for balneological and phytotherapy (application for invention of the Russian Federation 96108739/14). Mainly the mineral composition of this tool does not allow you to use it during the inflammation of the joint and periarticular tissues, and the low content of dimethyl sulfoxide removes the last only the role of substances that promote better penetration of mineral bischofite in the tissue.

Closest to the proposed solution and, therefore, selected as a prototype is a gel for the patent of the Russian Federation 2102980, class a 61 K 9/06, containing (wt.%): dimethyl sulfoxide (20-70), gelling component (1-5), glycerin (10-20), taurine (0,5-4,0), water (the rest). To obtain gels in this patent uses a variety of gel-forming substance is cellulose derivatives, gelatin, starch, polyvinylpyrrolidone, polyethylene glycols.

The disadvantage of the prototype can be noted that the gel-forming component plays only a passive role, as in all previous gels, the goal of treatment is selected, only the anti-inflammatory aspect.

The goal towards which sent the invention is to achieve a stronger effect local contradictory, envirovet the duration of the preservation of a satisfactory joint by improving the physico-chemical properties of the connective tissue structures of the synovial environment.

We offer a means for local Antirheumatic therapy allows to achieve local anti-inflammatory, analgesic, antioxidant and antihypoxic effects with simultaneous improvement in the structure of connective tissue formations articular and periarticular areas. The achievement of these effects is provided by the following composition (in wt. %): dimethyl sulfoxide (40-50), oxybutyrate lithium or sodium (0,2-0,4), local anesthetic (0,1-0,05), an antihistamine (0.05 to 0.1), gelatin (3-3,5), water (the rest).

The novelty of the proposed solution is that, first, the maintenance part of oxybutyrate allows to provide antihypoxic and antioxidant effect. With the introduction of lithium oxybutyrate achieved additional positive effect on metabolic processes in the affected joint due to lithium ions due to its ability to form soluble salts of uric acid, which is important for patients with impaired purine metabolism. The selected concentration of oxybutyrate 0.2-0.4 wt. % sufficient to achieve the antihypoxic and antioxidant effects, decreasing the concentration of these effects is not achieved. A further increase in the giving of the concentration of oxybutyrate may lead to the development of systemic manifestations in the form of inhibition, sleepiness. In the case of the use of lithium oxybutyrate by increasing the concentration there is the likelihood of toxic effects.

Secondly, the use of gelatin has a double aim - acceptable non-toxic of gelling and as substances that improve the physical and chemical condition of the connective tissue formations in the area of the affected joints, since gelatin is a product of partial hydrolysis of the major structural protein of connective tissue - collagen. The use of gelatin is available in any conditions and does not require special manufacturing costs. The amount of gelatin in the indicated concentrations of 3-3 .5 wt.% just enough to form a gel with optimal consistency properties, by increasing the concentration of the drug becomes inconvenient to use because of the excessive density of the colloid, at a lower concentration decreases the receipt quantity of collagen hydrolysate to connective tissue formations joints.

Third, the presence in this structure of local anesthetic provides rapid analgesic effect, in addition, local anesthetics possess the property of inhibitors of phospholipases, making a positive effect on the processes surgerychicago effect after a short period of time after application of the gel on the skin. Lower concentrations require longer time to reduce the pain, therefore, the analgesic effect occurs already from the effects of dimethyl sulfoxide. Increasing the concentration does not lead to increased analgesic effect.

Fourthly, the introduction of the antihistamine drug can partially prevent possible allergic reactions to the sulfoxide and other components of the gel, and also potentiates the analgesic and anti-inflammatory effects of the proposed tools.

The novelty of the proposed tools testifies to the creative nature of the decision, that is, speaks about the relevance of the proposed solutions to the criterion of "non-obviousness".

Example 1. Patient P., aged 47.

Diagnosis: Bilateral gonarthrosis, x-ray phase 2, reactive synovitis of the right knee joint, FTS 2 tbsp.

Companion: Obesity 2 degrees.

Pain in the knee joints of the mechanical rhythm was noted for 2 years before going to the doctor. Pain at rest in the right knee joint, joint swelling first appeared in April 1998, and therefore appealed to the rheumatologist. Upon examination of the knee was determined neznachitelny pain in the projection of the joint space and the lower medial Intesa. The amplitude of motion of the right knee joint was limited to 20 degrees due to the pain, the circumference of the right knee joint 44 see Left knee without signs of inflammation, palpation painless, the amplitude of movements in full, the circumference 42 cm

If ultrasonography revealed the presence of irregularities of the articular cartilage in both knees with a length of 9 mm to the right and 10 mm to the left, the thickness of the articular cartilage is not reduced in the right knee joint is determined by the effusion volume of 15 ml.

Performed remote computer thermography feet area revealed diffuse hyperthermia character in the projection of the right knee joint area of 420 K. E., weighted average temperature in this zone 30.7 degrees.

On radiographs of the knee in two projections is defined by a narrowing of joint cracks in the medial departments, the subchondral osteosclerosis, smoothness mimedecode exaltation.

Appointed gel according to the following recipe: demixed (40 wt%), lithium oxybutyrate (0.4 wt.%), diphenhydramine (0,05 wt.%), novocaine (0.08 wt.%), distilled water (the rest). Performed application 2 times a day.

After 2 weeks, when viewed from otmechennyh joints, pain on palpation periarticular points, still has a small pain on palpation of the joint cavity. Ultrasound of the knee amount of fluid in the cavity of the right knee joint 2 ml, left - 1 mil On thermal image indicates a significant decrease in the area and intensity of hyperthermia in the region of the right knee joint.

For the period subsequent monitoring of the patient (2 years) synovitis of the right knee joint not had anticipated. The patient continues to regularly use the gel as needed (usually in the evening after considerable physical exertion). The use of intra-articular injection of corticosteroids in this patient was not used even once.

Example 2. Patient K., 56 years old.

Diagnosis: Poliosteoartroz, nodular form, slowly progressive course, radiographic stage 3, recurrent synovitis of both knee joints, multiple periarthritis of both knee joints, FTS 2 tbsp.

Companion: Hypertension stage 2, outside of deterioration.

Suffering from osteoarthritis for more than 5 years, in connection with frequently recurrent synovitis during the year prior to treatment in Department the effect from intraarticular injection of kenalog was short, remained phenomena of periarthritis of the knee. In January 1999 for long-term systematic application in the form of applications assigned to the gel of the following composition: Dimexidum 45 wt.%, gelatin 3.5 wt.%, lidocaine 0.1 wt. % lithium oxybutyrate 0.2 wt.%, diphenhydramine is 0.05 wt.%, distilled water (the rest). At the control examination in April 1999, the patient had no episodes of recurrence of synovitis of the knee, making active movements, reducing the stiffness of the joints. Objectively recorded stabilization parameters on the level of discharge from hospital. In November 1999 after considerable physical exertion the patient noted an increase in the volume of the right knee joint, the appearance of a pain at rest, and therefore was hospitalized. In the hospital made one injection of kenalog in the right knee joint. For further treatment assigned to the proposed remedy. To date, the patient's condition is satisfactory, the recurrence of synovitis is not marked.

The proposed tool for local Antirheumatic therapy can be treated on an outpatient basis, as required for making the components available and the dash is nimoth".

A means for local Antirheumatic therapy containing dimethyl sulfoxide, gelatin and distilled water, characterized in that it contains oxybutyrate lithium or sodium, local anesthetic and antipruritic agent in the following ratio of ingredients, wt. %:

Dimethyl sulfoxide - 40-50

Gelatin - 3-3,5

Oxybutyrate lithium or sodium - 0,2-0,4

Local anesthetic - 0,1-0,05

Antihistaminic agent - 0,05-0,1

Distilled water - the Rest


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