RU2742172C2 - Combination of a chondroprotective agent with an nsaid - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to treatment of osteoporosis. Disclosed is the use of agent containing from 10 to 200 mg of diacerein, from 200 to 1000 mg of chondroitin and from 200 to 1000 mg of glucosamine for treating osteoporosis.

EFFECT: invention enables cartilage regeneration.

1 cl, 2 ex

Description

FIELD OF TECHNOLOGY

The present invention relates to a combined agent based on diacerein, chondroitin and glucosamine for oral use in the treatment of osteoarthritis of the peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontal disease and / or for accelerating the formation of callus in fractures.

LEVEL OF TECHNOLOGY

Diacerein (CAS 13739-02-1) is a non-steroidal anti-inflammatory drug, an anthraquinoline derivative, a diacetylated rhein derivative. Metabolized to the active metabolite of rhein, it inhibits the activity of interleukin-1, which plays an important role in the development of inflammation and cartilage degradation in osteoarthritis. Inhibits the action of other cytokines (including interleukin-6, TNFα). The action develops in 2-4 weeks. It has analgesic and anti-inflammatory activity when taken orally. After oral administration, it is rapidly absorbed from the gastrointestinal tract. With a single dose of 50 mg C _max in plasma - 3.15 mg / l, T _max - 144 minutes. Bioavailability increases by 25% when taken simultaneously with food. With repeated administration in connection with the cumulation of the drug, C _max in plasma increases. Fully deacetylated to rhein. The binding of rhein to plasma proteins (albumin) is almost 100%. T _1/2 - 255 min. It is excreted by the kidneys unchanged (20%), in the form of glucuronide (60%), in the form of sulfate - 20%.

Chondroitin (CAS 9007-27-6) is a biological polymer that acts as a flexible connecting matrix between protein strands in cartilage.

Glucosamine (CAS 3416-24-8, synonyms: 2-Amino-2-deoxy-beta-D-glucopyranose) is a substance produced by the cartilage tissue of the joints, is a component of chondroitin and is part of the synovial fluid, has chondroprotective properties, selectively acts on articular cartilage, is a specific substrate and stimulator of the synthesis of hyaluronic acid and proteoglycans, inhibits the formation of peroxide radicals and enzymes that damage cartilage tissue (collagenases and phospholipases). It is a monosaccharide in structure and serves as an important precursor in the biochemical synthesis of glycosylated proteins and lipids.

RF patent RU 2277902 C1 (publ. 20.06.2006) discloses a balm for relieving fatigue in the legs based on plant components, characterized in that it contains fructose, amaranth oil, glycerin, lysine, plant extracts, vitamin premix, vetoron (beta carotene), hermatronol (Astragerm), sodium benzoate, flavor (orange), antioxidant (Elite-C), carboxyethyl cellulose (Natrosol 250 farm.), thickener - Jaguar C14S, ethyl alcohol, glucosamine sulfate, acetylglucosamine, sodium hyaluronate and water a certain ratio of components. The balm normalizes the functional state of the vascular bed, restores blood circulation in the vessels and capillaries, increases the tone of the walls of blood vessels and capillaries, normalizes the processes of microcirculation while weakening the defenses in the inflammatory foci of vascular tissue, reduces swelling and pain syndromes.

RF patent RU 2376011 C1 (publ. 20.12.2009) discloses a means for caring for the area of peripheral joints and spine, including a complex of chondroprotectors, characterized in that it includes a liposomal concentrate with an antioxidant complex containing soy phospholipids, ethyl alcohol, troxerutin, sorbitol , glycerin, dihydroquercetin, vitamin PP (nicotinamide), 2-ethyl-6-methyl-3-hydroxypyridine succinate, 1-hydroxy germatran, 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline , tocopherol linoleate, magnesium ascorbyl phosphate, preservative and deionized water; microemulsion concentrate of organosilicon liquids containing organosilicon liquids, vegetable oils, soy phospholipids, oxyethylated vitamin E, glycerin, sorbitol, 2-ethyl-6-methyl-3-hydroxypyridine succinate, 1-hydroxy germatran, preservative and deionized water; an emulsion with a complex of nourishing vegetable oils; diethylene glycol monoethyl ether; 20-50% aqueous solution of bile; sodium hyaluronate mol. weighing 50-100 thousand Daltons and a complex perfumed thickener containing deionized water, glycerin, a thickener preservative and a fragrance at a certain content of components, where the chondroprotective complex can be a mixture of chondroitin sulfate (chloride), glucosamine sulfate (chloride), acetyl glucosamine at a certain content of components. The agent in the form of a nourishing balm cream is designed to slow down the progression of osteoarthritis, osteochondrosis, stimulate the restoration of articular cartilage, prevent further destruction of cartilage tissue, normalize the composition and production of intra-articular fluid, improve its lubricating properties, improve the mobility and function of the affected joints, activate blood circulation in the affected area joint, improve the nutrition of the articular cartilage area and have an anti-inflammatory effect.

International application WO 2010009474 A1 (publ. 01.21.2010) discloses a composition for treating abnormal conditions in a subject in which the abnormal condition affects the musculoskeletal joints, containing at least one omega-3 fatty acid, at least one glisoaminoglycan , at least one amino sugar, at least one antioxidant, and carnitine or acetylcarnitine. The amino sugar can be selected from the group consisting of galactosamine, glucosamine, sialic acid, and N-acetylglucosamine.

Eurasian patent EA 024725 B1 (publ. 12/30/2011) discloses compositions for skin rejuvenation and for topical treatment of acne and / or post-acne scars, comprising at least one oxidant selected from hydrogen peroxide, carbamide peroxide and benzoyl peroxide; at least one photoactivator consisting of eosin Y or a combination of eosin Y and one or more dyes selected from pyronine Y, pyronine B, rhodamine B, rhodamine G, rhodamine WT, fluorescein, phloxin B, rose Bengal, merbromine, eosin B, erythrosine, methyl violet, neutral red, para-red, amaranth, carmoisin, gait of red AC, tartrazine, orange G, ponso 4R, methyl red, purpuric ammonium murexide, safranin O, alkaline fuchsin, acid fuchsin, iodyl carboxylic acid, 3,3'-digexine acidic, green indocyanin, crocetin, a-crocin (8,8-diapo-8,8-carotenoid acid), zeaxanthin, lycopene, α-carotene, β-carotene, bixin, fucoxanthin, red saffron powder, annatto extract and brown extract algae, in combination with a pharmaceutically acceptable carrier, which may additionally include glucosamine.

International application WO 2012027797 A1 (publ. 03/08/2012) discloses a sterile aqueous composition for parenteral administration containing an effective amount of pentosan polysulfate (PPS) and hyaluronic acid (HA) or their salts, modified forms or mixtures thereof, the composition having a volume of less than 30 ml and pH less than 6.0 and includes at least one chelating agent, and may also include N-acetylglucosamine, glucosamine, glucosamine sulfate or glucosamine hydrochloride.

RF patent RU 2468805 C2 (publ. 10.12.2012) discloses a composition having an analgesic, anti-inflammatory effect and improving the functional state of the musculoskeletal system, containing glucosamine sulfate, chondroitin sulfate, methylsulfonylmethane, L-proline, ascorbic acid (vitamin C) , magnesium and additionally containing zinc gluconate, citric acid, sweetener, flavoring, preservative, water in certain proportions.

RF patent RU 2547572 C2 (publ. 10.04.2015) discloses a pharmaceutical composition for the treatment of diseases of the joints and bone tissues, containing a combination of active substances consisting of glucosamine sulfate salt, chondroitin sodium sulfate salt, ibuprofen as a non-steroidal anti-inflammatory agent, auxiliary substances from the number of fillers and technological additives and additionally containing vitamins and a calcium-containing agent-filler, and the components are contained in a certain ratio, which provides an increase in the therapeutic effect of the composition without increasing the amount and severity of side effects from its use.

Known drug CHONDROGLUSID (Owner of RU OJSC SINTEZ (Russia)) in the form of a gel for external use, containing 5 g of chondroitin sodium sulfate, 2.5 g of glucosamine hydrochloride, 0.05 g of sodium disulfite, 25 g of 96% ethanol, 10 g of propylene glycol , 3 g of carbomer (carbopol), 0.2 g of methyl parahydroxybenzoate, 0.05 g of lavender oil, purified water to 100 g for the treatment of stage I-III osteoarthritis (including joints and spine).

Known drug KONDRONOVA (Owner of RU Panacea Biotech Ltd (India)) in the form of an ointment for external use, containing 25 mg of glucosamine sulfate, 50 mg of chondroitin sulfate, 0.1 mg of butylhydroxytoluene, 0.5 mg of propyl parahydroxybenzoate, 1 mg of methyl parahydroxybenzoate, 70 mg mineral oil, 80 mg of white beeswax, 100 mg of lanolin, 673.4 mg of white soft paraffin, which is indicated for the treatment of osteochondrosis, osteoarthritis of peripheral joints and the spine.

Known drug HONDROGARD (Owner of RU ZAO PharmFirma Sotex (Russia)) in the form of a solution for intramuscular administration containing 100 mg of chondroitin sodium sulfate for the treatment of degenerative-dystrophic diseases of the joints and spine: osteoarthritis of the peripheral joints, intervertebral osteochondrosis, and osteoarthritis acceleration of the formation of callus in fractures.

Known drug MUKOSAT in the form of an ointment for external use (Owner of RU LLC "DIAMED-Pharma" (Russia)), containing 0.05 g of chondroitin sodium sulfate, 0.1 g of dimethyl sulfoxide. 0.15 g of lantonine, 0.5 g of petroleum jelly and water up to 1 g for the treatment of degenerative-dystrophic diseases of the joints and spine: osteoarthritis, intervertebral osteochondrosis; and in the form of a solution for intramuscular administration (FBU "State Institute of Medicines and Good Practices") containing 100 mg of chondroitin sodium sulfate and 9 mg of benzyl alcohol for the treatment of degenerative diseases of the joints and spine: osteoarthritis, arthropathy, intervertebral osteochondrosis.

In the prior art, there is no information about a combined agent based on diacerein, chondroitin and glucosamine for oral use in the treatment of osteoarthritis of peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontopathy and / or for accelerating the formation of callus in fractures.

The proposed agent has an anti-inflammatory effect. Stimulates the regeneration of cartilage tissue. Inhibits the synthesis and activity of IL-1, which plays an important role in the development of inflammation, degradation and subsequent destruction of cartilage in osteoarthritis, mainly due to diacerein, which is part of the composition. Slows down the formation of metalloproteinases (collagenases), which are involved in the process of damage to cartilage tissue. The recommended course is at least 4 months, up to 6 months. With prolonged use, it stimulates the synthesis of proteoglycans and does not affect the synthesis of prostaglandins. Takes part in the synthesis of connective tissue, helping to prevent the destruction of cartilage and stimulating tissue regeneration. Another action is the protection of damaged cartilage from metabolic destruction caused by NSAIDs and GCS, as well as its own moderate anti-inflammatory effect due to the glucosamine included in the composition. Contains an additional substrate for the formation of a healthy cartilage matrix. Stimulates the formation of hyaluronon, the synthesis of proteoglycans and collagen type II, and also protects hyaluronon from enzymatic degradation by suppressing the activity of hyaluronidase; maintains the viscosity of synovial fluid, stimulates cartilage repair mechanisms and inhibits the activity of those enzymes that break down cartilage (elastase, hyaluronidase). In the treatment of osteoarthritis, it relieves the symptoms of the disease and reduces the need for NSAIDs.

The combined agent according to the invention, due to the components included in its composition, has a synergistic effect of the active substances included in the agent.

SUMMARY OF THE INVENTION

The present invention relates to a new agent for oral use in the treatment of osteoarthritis of peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontal disease and / or for accelerating the formation of callus in fractures, containing diacerein, chondroitin and glucosamine.

In one embodiment, an agent of the invention may be a capsule. In one embodiment, an agent of the invention may be a sachet. In one embodiment, the agent of the invention may be a tablet.

In one embodiment, the agent according to the invention may further comprise auxiliary substances. The excipients can be stearic acid, magnesium stearate and / or manganese sulfate, sodium chloride, aspartame, sorbitol, citric acid and / or carbovax 4000, disubstituted calcium phosphate, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellulose, titanium dioxide (E171) and / or triacetin.

In one embodiment, an agent of the invention may contain: diacerein from about 10 to about 200 mg, chondroitin from about 200 to about 1000 mg, glucosamine from about 200 to about 1000 mg.

In addition, the present invention also relates to a new use of an agent containing diacerein, chondroitin and glucosamine for the treatment of osteoarthritis of the peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontal disease and / or for accelerating the formation of callus in fractures.

DETAILED DESCRIPTION OF THE INVENTION

There is a need in the art to provide alternatives to commercially available oral administration agents. Expansion of the arsenal of such means at the expense of the claimed means will allow to overcome the existing difficulties known to those skilled in the art and to reach a new level of joint treatment.

Osteoarthritis (osteoarthritis) is a degenerative-dystrophic disease of the joints, the cause of which is damage to the cartilage tissue of the articular surfaces. The term "osteoarthritis" unites a group of diseases of various etiologies, but with similar biological, morphological and clinical outcomes, in which the pathological process involves not only the articular cartilage, but the entire joint, including the subchondral bone, ligaments, capsule, synovial membrane and periarticular muscles. The main clinical symptoms of osteoarthritis are pain and joint deformity, leading to functional failure. At the heart of degenerative dystrophic changes in arthrosis is the primary damage to the cartilage followed by an inflammatory reaction, therefore arthrosis is often called arthrosis-arthritis. Osteoarthritis is always associated with deformation of bone tissue, in connection with which it is also called osteoarthritis or deforming arthrosis.

Osteoarthritis is the most common form of joint damage and one of the main causes of disability, causing a deterioration in the quality of life and significant financial costs, especially in the elderly. Most often, osteoarthritis affects the joints of the hand, the first metatarsophalangeal joint of the foot, joints of the cervical and lumbar spine, knee and hip joints. However, in terms of the severity of dysfunction of the musculoskeletal system, the first place is taken by the hip, knee and ankle joints, as well as the shoulder joint.

Osteoarthritis is a consequence of mechanical and biological causes that disrupt the formation of cells in the articular cartilage and subchondral bone. It can be initiated by many causes, including hereditary, evolutionary, metabolic, and traumatic. Osteoarthritis affects all joint tissues. The disease is manifested by morphological, biochemical, molecular and biomechanical changes in cells and matrix, which lead to softening, disfiguring, ulceration and a decrease in the thickness of the articular cartilage, as well as to osteosclerosis with a sharp thickening and compaction of the cortical layer of the subchondral bone, the development of subchondral cysts and cysts. Clinically, osteoarthritis is manifested by arthralgias, pain and limitation of movement, recurrent synovitis, local inflammation in various tissues of the joint.

Osteoarthritis is primary and secondary. If the cause of the development of the disease is not established, then such arthrosis is usually called primary, or idiopathic. Secondary osteoarthritis has an obvious cause: it develops after trauma, with metabolic disorders, endocrine diseases, as an outcome of a degenerative-necrotic process (aseptic necrosis of the femoral head, osteochondritis dissecans (Koenig's disease), Perthes disease), as an outcome of an inflammatory process (purulent inflammation of the joint , rheumatoid arthritis, arthritis with systemic lupus erythematosus, with tuberculosis).

Risk factors for primary osteoarthritis are: hereditary predisposition, overweight, old age, specific professions. In addition, the incidence of osteoarthritis depends on gender and race / ethnicity. Genetic factors include: hereditary disorders and mutations of type II collagen, other hereditary diseases of bones and joints, congenital joint developmental disorders (dysplasias). Non-genetic (non-inherited) multiple factors, such as age, osteoporosis, leave their mark on the development and progression of osteoarthritis; overweight; violation of the endocrine balance of the body, including a decrease in the secretion of estrogen (postmenopausal period); metabolic disorders in the body; deficiency in the body of trace elements; developmental disorders (dysplasia) and acquired diseases of bones and joints; neurodystrophic manifestations of the pathological process in the lumbosacral (lumbar-iliac muscle syndrome), or in the cervical spine (humeral-scapular periarthritis); inflammatory process in the joint.

The following risk factors for osteoarthritis are environmental factors: hypothermia; violation of ecological balance; the action of chemical toxins; joint injury, repetitive microtrauma; joint surgery (eg, meniscectomy); occupation and physical activity at work.

Regardless of the cause, there are 3 stages of arthrosis. At the first or initial stage of arthrosis, there are no pronounced morphological disorders of the joint tissues. Changes relate only to the function of the synovial membrane, to the biochemical composition of the synovial fluid, which, due to diffusion, nourishes the cartilage and menisci of the joint. The joint loses its ability to withstand the stress it is accustomed to, and overloading the joint is accompanied by inflammation and pain.

In the second stage of the disease, we see the incipient destruction of the articular cartilage and menisci. The bone reacts to the load of the articular platform with marginal growths - osteophytes.

The second stage inevitably turns into the third - the stage of severe arthrosis. Its signs are pronounced bone deformation of the joint support site, which changes the axis of the limb. Insufficiency, shortening of the ligaments of the joint leads to pathological mobility of the joint or, in combination with the rigidity of the joint capsule, to a sharp restriction of natural movements - contractures. Chronic inflammation and chronic pain usually accompany stages 2 and 3.

In the initial stage of the disease, the muscles that perform movements in the joint are weakened, but, in general, not changed. In the second stage, muscle dysfunction is observed due to a violation of reflex neurotrophic regulation. In the third stage of the disease, the loading of the joint and motor activity are sharply disturbed, due to contractures and violation of the limb axis, the amplitude of muscle contraction changes, and the normal points of attachment of the muscle-tendon complex change. This is accompanied by shortening or stretching of the muscle, a decrease in the ability to fully contract. Trophic disorders in joint disease concern not only muscles, but also all tissues of the limb.

The pathogenesis of this disease is based on a violation of the function and structure of the cartilage of the joint. Articular cartilage is a highly specialized tissue consisting of a matrix and chondrocytes embedded in it. The matrix contains two main macromolecules, glycosamines (proteoglycans) and collagen. The high concentration of proteoglycans in the cartilage keeps the collagen network under tension, thus contributing to an even distribution of the load that acts on the cartilage, and ensuring the restoration of shape after the load has ceased. With the loss of even a small amount of glycosamines, the resistance of the cartilage matrix to physical stress decreases, and the cartilage surface becomes susceptible to damage. In the earliest stages of arthrosis, the cartilage becomes thicker than normal, but as it progresses, it becomes thinner. Cartilage becomes soft and loose, and deep ulcers appear on it, usually only in the most stressed part of the joint.

Normally, under periodic loads, for example, when walking, the cartilaginous plate is deformed and returns to its previous shape, performing the function of a kind of pump that expels decay products and "absorbs" nutrients and building materials. Compression and restoration of shape under loading is the main condition for the regeneration of damaged cartilaginous tissue. However, excessive or prolonged loading of the joint adversely affects the function of the articular cartilage and aggravates the course of arthrosis.

The cartilage and menisci of the joint are nourished only by the synovial fluid. The "health" of the sliding and shock-absorbing structures of the joint depends on the quantity and quality of the fluid secreted by the synovium.

The synovial membrane performs an important function of filtering the building material of cartilage - hyaluronic acid, it prevents the latter from being washed out of the joint cavity. Violation of the biochemical composition of the synovial fluid in the event of injury or inflammation of the joint actually leads to the development of a disease called osteoarthritis.

The efficiency of the circulation and diffusion of the synovial fluid is directly related to the movement in the joint and the load on the joint. Joint movement is necessary for the metabolism of the cartilage. By itself, prolonged limitation of movement in the joint leads to a deterioration in cartilage nutrition.

With arthrosis, the balance between the formation of a new building material for cartilage restoration and its destruction is disturbed. Cartilage turns from a strong, elastic structure into a dry, thin structure with a rough surface. The underlying bone becomes thicker and expands away from the cartilage, which limits movement and causes joint deformation. The joint capsule thickens - fibroses, and also becomes inflamed. The joint is filled with an inflammatory fluid that stretches the capsule and joint ligaments. Pain, and later deformation of the articular surfaces in arthrosis leads to joint stiffness and joint contractures. Morning and starting pain, as well as stiffness in the joint in patients with deforming arthrosis, in fact, is due to the low elasticity of the cartilage and the need for starting movements to restore sufficient elasticity of the cartilage. This creates a feeling of pain and stiffness.

With inflammation, the joint assumes a resting or physiological position. In this position, the maximum expansion of the ligaments and the capsule of the joint is ensured. In this position, joint pain is minimal. The state of the so-called muscle corset of the joint has a great influence on the course of the pathological process, that is, the system of muscles that not only carries out movement in the joint, but also stabilizes the joint, absorbing powerful inertial impulses during movement. So, the internal broad muscle in the quadriceps of the thigh protects the knee joint from lateral instability at the moment of landing on the heel while walking, and the gluteus medius muscle on the side of the supporting leg limits the inclination of the pelvis at the time of transfer, which protects the hip joint from overload.

The outcome of arthrosis is the complete destruction of the joint with the formation of ankylosis - complete immobility of the joint or neoarthrosis with unnatural mobility. This is accompanied by severe limb dysfunction. Recently, without waiting for the outcome of the disease, more and more special operations are used to replace the joint with a prosthesis - joint arthroplasty. The figure shows a varus deformity of the knee, typical for the terminal stage of arthrosis of the knee joint, in combination with lateral pathological instability of the knee joint. Arthrosis of a block or ball joint, such as the hip, is completed with ankylosis. In this case, the closure of the joint usually occurs in the non-physiological (vicious) position of the limb. In this case, we see the hip in the flexion and adduction position, in which the leg is shortened, and the axis of the limb and the biomechanics of the musculoskeletal system are significantly disturbed. [URL: https://ru.wikipedia.org/wiki/Osteoarthritis].

Osteochondrosis is a complex of degenerative disorders in the articular cartilage. It can develop in almost any joint, but intervertebral discs are most often affected. Depending on the localization, cervical, thoracic and lumbar osteochondrosis are distinguished.

The root cause of spinal osteochondrosis is upright posture. In the process of growing up in humans, the vascular bed in the intervertebral discs is physiologically reduced, so their nutrition occurs diffusely. This complicates the restoration of intervertebral discs after injuries and stress. Inadequacy of the diet aggravates osteochondrotic processes. Cartilage loses its elasticity and strength, its shape and consistency change.

Irrational and asymmetrical work of the muscles of the spine negatively affects the discs, namely: with incorrect habitual postures, with insufficient warm-up, when carrying bags on the shoulder, when using soft pillows and mattresses. Flat feet can act as a stimulator of pathological processes. If the foot does not provide adequate cushioning of interactions with the support, the latter has to be done by the spinal column. Obesity also contributes to osteochondrosis of the spine. Excessive adipose tissue, deposited in different places, complicates the maintenance of balance and overloads the intervertebral joints. Complications of osteochondrosis include such diseases as: protrusion, disc herniation (intervertebral hernia, spinal hernia), kyphosis, radiculitis.

The causes of changes in the intervertebral discs are not fully understood. People begin to feel manifestations of osteochondrosis most often after 35 years. Various back injuries, static and dynamic overloads, as well as vibration contribute to the development and exacerbation of this ailment. The older a person is, the more manifestations he has. But in recent years, more and more people between the ages of 18 and 30 are complaining of back pain. There are many reasons for the early manifestation of the disease: poor physical fitness, poor posture and curvature of the spine, flat feet and overweight. The main reasons are: hereditary (genetic) predisposition; metabolic disorders in the body, infection, intoxication; overweight; improper diet (lack of trace elements and fluid); age-related changes; spinal injuries (bruises, fractures); postural disorder, curvature of the spine, hypermobility (instability) of the segments of the spinal column, flat feet; unfavorable environmental conditions; sedentary lifestyle; work associated with lifting weights, frequent changes in the position of the body (turns, flexion and extension, jerking movements); prolonged exposure to uncomfortable postures in a standing, sitting, lying position, when lifting and carrying weights, when performing other work, in which the pressure in the discs and the load on the spine as a whole increase; excessive physical activity, unevenly developed musculoskeletal system; overload of the spine associated with foot diseases, as well as as a result of wearing uncomfortable shoes, high heels and pregnancy in women; abrupt cessation of regular training by professional athletes; nervous overstrain, stressful situations; smoking.

Patients suffering from osteochondrosis complain of constant aching back pain, which is often accompanied by numbness and aching in the limbs. In the absence of adequate treatment, weight loss and atrophy of the limbs occurs. The main symptoms: constant aching back pain, feeling of numbness and aches in the limbs; increased pain with sudden movements, physical exertion, lifting weights, coughing and sneezing; decreased range of motion, muscle spasms; with osteochondrosis of the cervical spine: pain in the arms, shoulders, headaches; development of the so-called vertebral artery syndrome is possible, which consists of the following complaints: noise in the head, dizziness, flashing "flies", colored spots in front of the eyes in combination with a burning throbbing headache. The cause of the vertebral artery syndrome can be its spasm in response to both direct irritation of its sympathetic plexus due to bony growths, disc herniation, arthrosis of the intervertebral joint, and a reflex reaction due to irritation of any receptors of the spine. The presence of vertebral artery syndrome can aggravate the course of coronary or cardiomuscular pathology, if present; with osteochondrosis of the thoracic spine: pain in the chest (like a "stake" in the chest), in the region of the heart and other internal organs; with osteochondrosis of the lumbosacral spine: lower back pain, radiating to the sacrum, lower extremities, sometimes to the pelvic organs; defeat of the nerve roots (with herniated intervertebral discs, bone growths, spondylolisthesis, spondyloarthrosis): shooting pain and impaired sensitivity, hypotrophy, hypotension, weakness in the innervated muscles, decreased reflexes.

Establishment of a preliminary diagnosis is carried out during the initial examination of the patient. The examination is usually carried out by a neurologist in connection with the patient's complaints about local changes, which can be manifested by pain, deformity or limited mobility. The spine is examined with the patient standing, sitting and lying down, both at rest and in motion. The level of spinal lesion is determined by counting the number of vertebrae from certain anatomical landmarks or according to a special scheme. When examining the back, pay attention to the posture, structural features of the trunk, mark the line of spinous processes (median groove of the back), lower angles of the shoulder blades, crests of the iliac bones, lateral contours of the waist and neck, position of the shoulder girdle, deviation of the intergluteal groove from the vertical, reveal protrusion, protrusion of the spinous processes pay attention to the relief of the muscles located next to the spine. Feeling the spine allows you to supplement the examination data (presence or absence of deformity), to determine the localization, degree and nature of pain. When palpating, the tension of the muscles located next to the spine is also noted. most injuries and diseases of the spine are accompanied by increased muscle tone. Spinal flexion is used to determine the range of motion in various parts of the spine. The main role in the study of the spine is assigned to radiography, computed tomography and magnetic resonance imaging, with the help of which the level of damage is determined, the diagnosis is clarified and concretized, and hidden pathologies are revealed. Diagnostic data allow the attending physician to determine the tactics of treatment and choose the most effective treatment methods. [URL: https://ru.wikipedia.org/wiki/Osteochondrosis]

Spondyloarthrosis is a particular form of osteoarthritis, which is a heterogeneous form of diseases, different in clinical presentation and outcomes, which are based on the defeat of all the constituent elements of the joint - cartilage, subchondral bone, ligaments, capsule and periarticular muscles. The most common localization of osteoarthritis is arthrosis of the knee and hip joints, as well as the spine. In the latter case, both the joints between the vertebral bodies and the facet (facet) joints of the vertebral segments are affected.

Spondyloarthrosis is not only a disease of the elderly, although in the latter case it is observed in 85-90%. In young people, arthritic changes in the spine can develop after 25-30 years, which is facilitated by congenital anomalies of the spine, hypermobility of the vertebral segments and, of course, trauma.

A) Anomalies such as the presence of transitional lumbosacral vertebrae contribute to the early onset of arthrosis; lumbarization, i.e. the presence of the 6th lumbar vertebra due to the upper sacral segment or, conversely, sacralization, i.e. fusion of the 5th lumbar vertebra with the sacrum. An important role (in the appearance of recurrent back pain) is played by a violation of articular tropism, i.e. asymmetric location of the facet joints.

The linear arrangement of the facet joints deserves special attention. In the cervical region, the facets are located horizontally (transversely), with a very slight posterior-inferior deviation. In the thoracic region, the facet joints are located at a lower level (in relation to the vertebral body) and can be compared with the location of the nerve root (horizontal in the neck and going downwards on the thoracic). In the lumbar spine, the facet joints are located sagittally at the first and second vertebrae and almost coronary (i.e. parallel to the coronary suture or - trying to take a perpendicular position to the lateral surface of the vertebral body) in the 3-5th vertebrae. Sometimes the facet joint is located on one side in the sagittal plane, and on the other side in the coronary plane. Such anomalies of "tropism" occur in many people and are considered a predisposing factor for additional rotational load on them.

Small anomalies are so widespread that they can be recorded in almost every second person.

"Transitional vertebra" - in addition to facet tropism anomalies, a change in the number of movable vertebrae at the lumbar level is the most significant among the causes of pain. Lumbarization of the first sacral vertebra increases the "lever arm" for the lumbar and causes increased stress on the lumbosacral articulation. Sacralization of the fifth lumbar vertebra is unlikely to cause pain if the vertebra is firmly connected to the sacrum. However, if sacralization is unilateral, the load on the vertebra becomes abnormal. The most common form of sacralization is when one transverse process of the fifth lumbar vertebra is enlarged and is connected by a joint to the sacrum. The axis of movement on the side of the joint is shifted from the sagittal plane of such a joint and the excursion on the opposite side of the vertebra increases. This can cause tension on the side opposite to sacralization.

Two anomalies - the sixth lumbar vertebra and sacralization of the fifth vertebra - are clinically significant and may be contraindications to certain professions. The diagnosis is easily established by x-ray.

"Spina bifida occulta" refers to the non-closure of the arches of the lumbar vertebrae. The anomaly is so common that it can be considered a variant of the anatomical norm.

B) Trauma is a very common cause of lower back pain. Often, it is facilitated by insufficient physical condition of the individual. Most muscle sprains and low back pain can be prevented by weight control, daily exercise and regular sports activity (depending on age and physical condition). Athletes and young healthy people relatively rarely injure the lower back, because they are in good physical shape. However, most people after 30 years of age reduce physical activity, gain weight and do not pay attention to physical exercise. When they have to deal with physical activity, it is often excessive for them. So, a person sitting at a desk five days a week cannot count on a successful tennis game.

Traumatic facet joint subluxation is one of the most common causes of lower back pain. This pathology is best diagnosed and treated by chiropractic methods.

Spondylolysis and spondylolisthesis are referred to by many as stress fractures of the "isthmus" or "inter-articular region" of the vertebra. Spondylolysis is a defect of the isthmus, spondylolisthesis is a bilateral defect with anterior slipping of the body of the affected vertebra and the transverse processes of the underlying vertebra. Thus, in spondylolisthesis, the posterior parts of the vertebra (spinous process and arches) remain in a normal position. The degree of slippage ranges from grade 1 to grade 4. 1st degree - displacement from 0 to 25% and 4th - complete anterior displacement of the vertebra. The fifth lumbar vertebra is most commonly affected, followed by the fourth lumbar vertebra.

In oblique X-ray projection, the normal vertebra appears as a "spaniel in profile". If such a "spaniel" has a "collar", one can speak of spondylolysis; if "the dog's head is separated from the body" - there is spondylolisthesis.

Spondylolisthesis is usually a minor issue, with irregular, occasional low back pain as the only symptom. However, in active teenagers, the problem can be more serious, especially as spondylolisthesis progresses. Further slipping can cause severe root compression and stabilization of the vertebral segments is required.

C) Vertebral instability is an independent nosological unit; the lumbar vertebra is displaced backward or forward in relation to the underlying vertebra. Usually occurs between the third and fourth and between the fourth and fifth lumbar vertebrae. Usually the displacement is anterior and occurs when bending.

Easily diagnosed with functional X-rays. Surgery is usually not indicated because there is often multiple instability.

The phenomenon of osteoarthritis is characterized as "wear (get tired) and cry"; it is associated with degenerative changes in articular cartilage. The facet joints in the spinal column are affected. Repeated injuries over a number of years (adolescence and young age) play a certain role, but they cannot fully explain the onset of the disease. Heredity and increased weight contribute to the disease. An analogy is drawn with the use of a car - the more and longer it is used, the more often it starts to "junk".

Under the influence of static-dynamic loads, the elastic gelatinous nucleus of the intervertebral disc, which plays a shock-absorbing role and provides the flexibility of the spine, begins to lose its physiological properties due, first of all, to depolarization of saccharides in the nucleus. In conditions of altered, increased mobility of the vertebral segment (instability), reactive changes occur in the adjacent vertebral bodies and in the joints - spondyloarthrosis accompanying osteochondrosis develops.

The vertebral segment includes not only the cartilaginous disc between the adjacent vertebrae and facet joints, but also the ligaments and muscles connecting them - the intertransverse, interspinous and rotator cuff muscles. These muscles, under the influence of impulses from the affected vertebral segment, especially from the posterior longitudinal ligament, reflexively tense; their asymmetric tension causes curvature of the spine - scoliosis, which doctors often observe in patients with spondyloarthrosis.

The main clinical manifestation of osteoarthritis is pain that occurs when moving, changing the posture of the trunk and passing at rest; but, as the disease progresses, morning stiffness appears, lasting 20-60 minutes. In the case of joint subluxation or spondylolisthesis, arthritic (inflammatory) processes and reflex muscle-tonic reactions develop, causing pain and limited mobility of the spine, lasting several weeks or months.

A specific situation is diagnosed according to clinical criteria and X-ray, in particular, computed tomography data. [Gorbacheva F.E. Spondyloarthrosis of the spine: diagnosis and treatment. M., 2007. 12 p.]

At the heart of degenerative dystrophic changes in arthrosis is the primary damage to the cartilage followed by an inflammatory reaction, therefore arthrosis is often called arthrosis-arthritis. Osteoarthritis is always associated with deformation of bone tissue, in connection with which it is also called osteoarthritis or deforming arthrosis.

The present invention relates to a new agent, or drug, or composition, or pharmaceutical composition, or preparation for oral use in the treatment of osteoarthritis of the peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontopathy and / or for accelerating the formation of callus in fractures, containing diacerein , chondroitin and glucosamine.

The agent according to the invention can be a capsule, or a sachet, or a tablet.

The agent according to the invention may additionally contain auxiliary substances. The excipients can be stearic acid, magnesium stearate and / or manganese sulfate, sodium chloride, aspartame, sorbitol, citric acid and / or carbovax 4000, disubstituted calcium phosphate, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellulose, titanium dioxide (E171) and / or triacetin.

The agent according to the invention may contain: diacerein from about 10 to about 200 mg, chondroitin from about 200 to about 1000 mg, glucosamine from about 200 to about 1000 mg.

In addition, the present invention also relates to a new use of an agent containing diacerein, chondroitin and glucosamine for the treatment of osteoarthritis of the peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontal disease and / or for accelerating the formation of callus in fractures.

The tool in the form of hard gelatin capsules according to the present invention may contain, mg:

Diacerein from about 10 to about 200 Chondroitin from about 200 to about 1000 Glucosamine from about 200 to about 1000

In particular, the agent according to the present invention may contain, mg:

Diacerein fifty Chondroitin 400 Glucosamine 500

In particular, the agent according to the present invention may further comprise one or more of, mg:

Stearic acid ten Magnesium stearate five Manganese sulfate one

In particular, the composition of the gelatin capsule is: gelatin 120 mg.

An agent in the form of a sachet according to the present invention may contain, mg:

Diacerein from about 10 to about 200 Chondroitin from about 200 to about 1000 Glucosamine from about 200 to about 1000

In particular, the agent according to the present invention may contain:

Composition No. 1:

Diacerein 50 mg Chondroitin 400 mg Glucosamine 500 mg

Composition No. 2:

Diacerein 100 mg Chondroitin 800 mg Glucosamine 1000 mg

Composition No. 3:

Diacerein 100 mg Chondroitin 1000 mg Glucosamine 1500 mg

In particular, the agent according to the present invention may additionally contain one or more of: sodium chloride, aspartame, sorbitol, citric acid, carbovax 4000.

An agent in the form of a tablet according to the present invention may contain, mg:

Diacerein from about 10 to about 200 Chondroitin from about 200 to about 1000 Glucosamine from about 200 to about 1000

In particular, the agent according to the present invention may contain, mg:

Diacerein fifty Chondroitin 500 Glucosamine 500

In particular, the agent according to the present invention may additionally contain one or more of: calcium phosphate disubstituted, microcrystalline cellulose (MCC), magnesium stearate, stearic acid, croscarmellose sodium, hydroxypropyl methylcellulose, titanium dioxide (E171), triacetin.

EXAMPLES

The examples included in the present description are not limiting of the claimed invention and are provided only for the purpose of illustration and confirmation of the achievement of the expected technical results. These examples are one of many experimental data obtained by the inventors that confirm the effectiveness of oral administration agents within the scope of the invention.

Example 1. Obtaining an agent according to the invention and a comparator.

1. Get agent A in capsules containing, mg:

Diacerein fifty Chondroitin 400 Glucosamine 500

2. Get agent B in capsules containing, mg:

Diacerein fifty Chondroitin 400 Glucosamine 500

Example 2. Use of an agent according to the invention and a comparator.

Obtained in Example 1, the funds were used to evaluate the therapeutic efficacy in patients suffering from primary osteoarthritis of the knee joint, by assessing the thickness of the cartilage, the intensity of pain and the quality of life of patients before and after treatment.

The study included 28 patients with osteoarthritis of the knee joint (14 men aged 45 to 70 years and 14 women aged 50 to 70 years).

Determination of the stage of osteoarthritis according to its severity was performed in accordance with the point assessment. The entire surveyed population showed the II X-ray stage of the disease.

When included in the group and after a few months, a history of the disease was carried out with the collection of data and the following parameters were assessed: the intensity of pain on a visual analogue scale, assessed by both the doctor and the patient; the severity of the disease using the questionnaire; the thickness of the knee joint cartilage by ultrasound scanning.

Analysis of the results of the study showed an improvement in clinical symptoms after administration of both agent A according to the invention and agent B. However, in the case of agent A, this improvement took place only after 2 months and persisted after 5 months with a further beneficial effect on osteoarticular symptoms. The pain scores for agent A decreased significantly from baseline, demonstrating that agent A not only increases the viscoelasticity of synovial fluid, but also has a beneficial effect on pain symptom and patient quality of life.

Claims (1)

The use of a product containing 10 to 200 mg of diacerein, 200 to 1000 mg of chondroitin and 200 to 1000 mg of glucosamine for the treatment of osteoporosis.