WO2019004868A2

WO2019004868A2 - Combination of a chondroprotective agent with an nsaid

Info

Publication number: WO2019004868A2
Application number: PCT/RU2018/000345
Authority: WO
Inventors: Алексей Валерьевич ЧЕКАЛОВ
Original assignee: Общество с ограниченной ответственностью "ФБК"
Priority date: 2017-06-30
Filing date: 2018-06-28
Publication date: 2019-01-03
Also published as: RU2017123275A3; RU2017123275A; RU2742172C2; WO2019004868A3

Abstract

The invention relates to an oral agent containing diacerein, chondroitin and glucosamine, and to the use of same to treat osteoarthritis of the peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontitis and/or for accelerating callus formation in fractures.

Description

COMBINATION OF HONDROPROTECTIVE MEANS WITH NSAID

TECHNICAL FIELD

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 to accelerate the formation of callus during fractures.

BACKGROUND

Diacerein (C AS 13739-02-1) is a nonsteroidal anti-inflammatory drug, an anthraquinoline derivative, a diacetylated reina derivative. Metabolizing to the active metabolite Rein, inhibits the activity of interleukin-1, which plays an important role in the development of inflammation and degradation of cartilage in osteoarthritis. Inhibits the action of other cytokines (including interleukin-6, TNF). The action develops in 2-4 weeks. It has analgesic and anti-inflammatory activity when taken orally. After ingestion is rapidly absorbed from the gastrointestinal tract. With a single dose of 50 MG max in plasma - 3.15 mg / l, Ttah - 144 min. Bioavailability is increased by 25% when taken with food. With repeated use in connection with the accumulation of the drug Schakh In plasma increases. Completely deacetylated to reina. Rein binding to plasma proteins (albumin) is almost 100%. TT - 255 min. Excreted by the kidneys in unchanged form (20%), as glucuronide (60%), as sulfate - 20%.

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

Chondroitin

Glucosamine (CAS 3416-24-8, synonyms: 2-Amino-2-deoxy-beta-0-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, acts selectively 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 (collagenase and phospholipase). The structure is a monosaccharide, serves as an important precursor in the biochemical synthesis of glycosylated proteins and lipids.

Glucosamine

In the patent of the Russian Federation RU2277902C1 (published on 06/20/2006) a balm for relieving fatigue in the legs based on herbal ingredients is disclosed, characterized in that contains fructose, amaranth oil, glycerin, lysine, plant extracts, vitamin premix, vetoron (beta-carotene), germatronol (Astragherm), sodium benzoate, flavoring (orange), antioxidant (Elite-C), carboxyethylcellulose (Natrosol 250 ph.) , thickener - Jaguar C14S, ethyl alcohol, glucosamine sulfate, acetylglucosamine, sodium hyaluronate and demineralized water at a certain ratio of components. Balsam normalizes the functional state of the vascular bed, restores blood circulation in vessels and capillaries, increases the tone of the walls of blood vessels and capillaries, normalizes microcirculation processes while weakening the protective forces in inflammatory foci of vascular tissue, reduces puffiness and pain syndromes.

RF patent RU2376011C1 (published on 12/20/2009) discloses a means for caring for the area of peripheral joints and the spine, including a complex of chondroprotectors, characterized in that it includes a liposomal concentrate with an antioxidant complex containing soybean phospholipids, ethyl alcohol, troxerutin, sorbitol, glycerol , dihydroquercetin, vitamin PP (nicotinamide), 2-ethyl-6-methyl-3-hydroxypyridine succinate, 1-hydroxy hermatrane, 6-ethoxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline, tocopherol linoleate, magnesium ascorbyl phosphate, preservative and water deion izirovannuyu; microemulsion concentrate of silicone fluids containing silicone fluids, vegetable oils, soybean phospholipids, ethoxylated vitamin E, glycerin, sorbitol, 2-ethyl-6-methyl-3-hydroxypyridine succinate, 1-hydroxy hermatran, preservative and deionized water; 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. Dalton and complex perfumed thickener containing deionized water, glycerin, preservative thickener and fragrance at a certain content of components, where the complex of chondroprotectors can be a mixture of chondroitin sulfate (chloride), glucosamine sulfate (chloride), acetyl glucosamine at a certain content of components. Means in the form of a nutritional cream-balm is designed to slow the progression of osteoarthritis, osteochondrosis, stimulate the recovery of articular cartilage, prevent further destruction of cartilage tissue, normalize the composition and production of intraarticular fluid, improve its lubricating properties, improve mobility and function of the affected joints, enhance

s blood circulation in the area of the affected joint, improve the nutrition of the articular cartilage and have an anti-inflammatory effect.

In the international application WO2010009474 A 1 (publ. 01/21/2010) a composition is disclosed for treating abnormal conditions in a subject in which an abnormal condition affects musculoskeletal joints, containing at least one omega-3 fatty acid, at least one glizoaminoglykan , at least one amino sugar, at least one antioxidant, and carnitine or acetylcarnitine. The aminosugar may be selected from the group consisting of galactosamine, glucosamine, sialic acid, and Ν-acetylglucosamine.

The Eurasian patent EA024725B1 (published on 12/30/2011) discloses compositions for skin rejuvenation and for the topical treatment of acne and / or scars after acne, including 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 pyronin Y, pyronin B, rhodamine B, rhodamine G, rhodamine WT, fluorescein, phloxin B, rose Bengal, merbromine, eosin B, erythrosine, metilvioleta, neutral red, parakrasnogo, amaranth, karmoizina, gait red AC, tartrazine, orange G, Ponceau 4R, methyl red, purpurovokislogo ammonium murexide, Safranin O, alkali fuchsin, acid fuchsin, iodide 3,3'-digeksilkarbotsianina, carmine kitty green, indocyanine green, crocetin, α-crocin (8,8-diapo-8,8-carotenoid acid), zeaxanthin, lycopene, a-carotene, β-carotene, bixin, fucoxanthin, red saffron powder, annato extract and brown extract algae, in combination with a pharmaceutically acceptable carrier, which may additionally include glucosamine.

In the international application WO2012027797 A 1 (published on March 8, 2012) a sterile aqueous composition for parenteral administration is disclosed containing an effective amount of pentosan polysulfate (PPS) and hyaluronic acid (NA) or their salts, modified forms or mixtures thereof, and the composition has a volume less than 30 ml and pH less than 6.0 and includes at least one chelating agent, and may also include α-acetylglucosamine, glucosamine, glucosamine sulfate or glucosamine hydrochloride.

In the patent of the Russian Federation RU2468805C2 (publ. 10.12.2012) a composition is disclosed that has anesthetic, anti-inflammatory effect and improves 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 agent, preservative, water at certain ratios.

In the RF patent RU2547572C2 (publ. 10.04.2015) a pharmaceutical composition for the treatment of diseases of the joints and bone tissues is disclosed, containing a combination of active substances consisting of glucosamine sulfate salt, chondroitin sodium sulfate salt, ibuprofen as a non-steroidal anti-inflammatory agent, excipients among fillers and technological additives and additionally containing vitamins and calcium-containing agent-filler, and the components are contained in a certain ratio, which ensures usi the treatment of the therapeutic effect of the composition without increasing the number and severity of side effects from its use.

Known drug HONDROGLUKSID (Owner of RU SYNTEZ OJSC (Russia)) in the form of a gel for topical 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, water purified to 100 g for the treatment of osteoarthrosis stage I-III (including joints and spine).

Known medicament KONDROnova (Holder RC Panacea Biotec Ltd. (India)) in the form of ointments for external application containing 25 mg glucosamine sulfate, chondroitin sulfate, 50 mg, 0.1 mg of BHT, 0.5 mg propyl parahydroxybenzoate, methyl parahydroxybenzoate 1 mg, 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 RP CJSC FarmFirma Soteks (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 peripheral joints, intervertebral osteochondrosis and osteoarthritis and osteoarthrosis of osteoarthritis, osteoarthrosis of peripheral joints, intervertebral osteochondrosis and osteoarthritis and osteoarthrosis of osteoarthritis of osteoarthritis of the peripheral joints accelerate the formation of callus in fractures.

Known drug MUKOSAT in the form of an ointment for external use (Owner RU OOO "DIAMED-pharma" (Russia)) containing 0.05 g chondroitin sodium sulfate, 0.1 g of dimethyl sulfoxide. 0.15 g of lanthonine, 0.5 g of vaseline and water up to 1 g for the treatment of degenerative-dystrophic diseases of the joints and spine: osteoarthrosis, intervertebral osteochondrosis; and in the form of a solution for intramuscular injection (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: osteoarthrosis, arthropathy, intervertebral osteochondrosis.

In the prior art there is no information about the combined tool 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 to accelerate the formation of callus during fractures.

The proposed tool has 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. Slows the formation of metalloproteinases (collagenases), which are involved in the process of cartilage damage. Recommended course of not less than 4 months, up to 6 months. With prolonged use 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 processes of cartilage destruction and stimulating tissue regeneration. Another action is to protect the damaged cartilage from metabolic destruction caused by NSAIDs and GCS, as well as its own moderate anti-inflammatory effect due to the glucosamine. Contains an additional substrate for the formation of a healthy cartilage matrix. Stimulates the formation of hyaluronon, the synthesis of proteoglycans and type II collagen, and also protects hyaluronon from enzymatic degradation by suppressing the activity of hyaluronidase; maintains the viscosity of synovial fluid, stimulates the mechanisms of cartilage repair 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 tool according to the invention due to the components in its composition, has a synergistic effect included in the tool of active substances.

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

In one embodiment, the agent according to the invention may be a capsule. In one embodiment, the agent according to the invention may be a sachet. In one embodiment, the agent according to the invention may be a tablet.

In one embodiment, the agent according to the invention may additionally contain auxiliary substances. The auxiliary substances can be stearic acid, magnesium stearate and / or manganese sulfate, sodium chloride, aspartame, sorbitol, citric acid and / or carbovax 4000, calcium phosphate disubstituted, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmalloser and a sample of croscarmellostellar drawing. dioxide (E171) and / or triacetin.

In one embodiment, 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 peripheral joint osteoarthrosis, intervertebral osteochondrosis, osteoarthrosis and osteoporosis, periodontal disease and / or to accelerate the formation of bone callus during fractures.

DETAILED DESCRIPTION OF THE INVENTION

In this field of technology there is a need for the provision of alternatives available on the market for oral administration. The expansion of the arsenal of such funds at the expense of the stated funds will allow to overcome the existing difficulties known to specialists in this field of technology, and to reach a new level of joint treatment.

Osteoarthritis (osteoarthritis) is a degenerative-dystrophic disease of the joints, caused by damage to the cartilage tissue of the articular surfaces. The term “osteoarthrosis” unites a group of diseases of various etiologies, but with similar biological, morphological and clinical outcomes in which not only the articular cartilage is involved in the pathological process, but the entire joint, including the subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles. The main clinical symptoms of osteoarthritis are pain and deformity of the joints, leading to functional failure. The basis of degenerative dystrophic changes in arthrosis is the primary damage to the cartilage, followed by an inflammatory reaction, so arthrosis is often called arthrosis-arthritis. Arthrosis is always associated with deformation of the bone tissue, and therefore 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, the joints of the cervical and lumbar spine, knee and hip joints. However, the severity of dysfunction of the musculoskeletal system, the first place is occupied 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 articular cartilage cells and subchondral bone. It can be triggered by many causes, including hereditary, evolutionary, metabolic, and traumatic. Osteoarthritis affects all tissues of the joints. The disease is manifested by morphological, biochemical, molecular and biomechanical changes in cells and matrix, which lead to softening, wrinkling, ulceration and reduction of the thickness of articular cartilage, as well as osteosclerosis with a sharp thickening and compaction of the cortical layer of the subchondral bone, osteophytes, and I’ll get to have fun. Osteoarthrosis is clinically manifested by arthralgia, soreness and restriction of movements, recurrent synovitis, local inflammation in various tissues of the joint.

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

Risk factors for primary osteoarthritis are: genetic predisposition, overweight, advanced age, specific occupations. In addition, the incidence of osteoarthritis depends on gender and race / ethnicity. Genetic factors include: hereditary disorders and mutations of collagen type II, other hereditary diseases of bones and joints, congenital disorders of joint development (dysplasia). Imprint on the development and progression of osteoarthritis non-genetic (non-inherited) multiple factors, such as: age, osteoporosis; overweight; disruption 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; impaired development (dysplasia) and acquired diseases of bones and joints; neurodystrophic manifestations of the pathological process in the lumbosacral (syndrome of the lumbar-iliac muscle), or in the cervical spine (shoulder-scapular periarthritis); inflammatory process in the joint.

The following risk factors for osteoarthritis are environmental factors: hypothermia; ecological imbalance; the action of chemical toxins; joint injury, recurring 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 tissues of the joint. The changes relate only to the function of the synovial membrane, to the biochemical composition of the synovial fluid, which, due to diffusion, nourishes cartilage and menisci of the joint. The joint loses its ability to withstand its usual load, and the joint overload is accompanied by inflammation and pain.

In the second stage of the disease, we see the beginning destruction of articular cartilage and menisci. The bone responds to the load of the articular area with marginal growths — osteophytes.

The second stage inevitably turns into the third stage of severe arthrosis. Its signs are pronounced bone deformity of the joint supporting area, which changes the axis of the limb. The failure, shortening of the ligaments of the joint leads to the pathological mobility of the joint or in combination with the stiffness of the articular bag— to a sharp restriction of natural movements — contractures. Chronic inflammation and chronic pain syndrome usually accompany stage 2 and 3.

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

The basis of the pathogenesis of this disease is the 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 immersed in it. The matrix contains two major macromolecules, glycosamines (proteoglycans) and collagen. The high concentration of proteoglycans in the cartilage keeps the collagen network under tension, thus contributing to the even distribution of the load that affects the cartilage, and ensuring the recovery of the shape after the load is terminated. With the loss of even a small amount of glycosamines, the resistance of the cartilage matrix to the effects of exercise decreases, and the surface of the cartilage becomes susceptible to damage. In the very early stages of arthrosis, the cartilage becomes thicker than normal, but as it progresses, it becomes thinner. The cartilage becomes soft and loose, deep ulcers appear on it, usually only in the most loaded part of the joint.

Normally, with periodic loads, for example, when walking, the cartilage plate deforms and returns to its former form, performing the function of a kind of pump that provides for pushing out decomposition products and “sucking” nutrients and building material. Compression and recovery of the form under loading is the main condition for the regeneration of damaged cartilage tissue. However, excessive or prolonged loading of the joint adversely affects the function of the articular cartilage and aggravates the course of arthrosis.

Nutrition of the cartilage and meniscus of the joint is carried out only at the expense of synovial fluid. The “health” of the sliding and damping structures of the joint depends on the quantity and quality of the fluid secreted by the synovial membrane. Yu The synovial membrane performs an important function of filtering the building material of cartilage — hyaluronic acid; it prevents the latter from leaching out of the joint cavity. Violation of the biochemical composition of synovial fluid in case of injury or inflammation of the joint actually leads to the development of a disease called osteoarthritis.

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

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

In inflammation, the joint assumes a resting or physiological position. At this position, the maximum expansion of the ligaments and the capsule of the joint is ensured. In this position, the pain in the joint is minimal. The state of the so-called muscular corset of the joint, 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, has a great influence on the pathological process. Thus, the internal wide muscle in the quadriceps of the thigh protects the knee joint from lateral instability at the time of landing on the heel when walking, and the gluteus maximus on the side of the supporting leg limits the pelvic tilt at the moment of transfer, which prevents the hip joint from overloading.

The outcome of osteoarthritis 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 dysfunction of the limb. Recently, not Waiting for the outcome of the disease, special procedures are often used to replace the joint with a prosthesis — endoprosthetics of the joint. The figure shows a typical for the terminal stage of arthrosis of the knee joint varus deformity of the knee in combination with lateral pathological instability of the knee joint. Osteoarthritis of a blocky or spherical joint, such as the hip joint, is completed by ankylosing. 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 position of flexion and adduction, 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/OcTeoapTpo3]

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

The root cause of spinal osteochondrosis is upright walking. In the process of maturation in humans, the vascular bed in the intervertebral discs is physiologically reduced, therefore their nutrition occurs diffusely. This complicates the restoration of intervertebral discs after injuries and loads. The inadequacy of the diet exacerbates osteochondrotic processes. Cartilage loses its elasticity and strength, changes its shape and texture.

Irrational and asymmetrical work of the spinal muscles negatively affects the discs, namely: with improper customary postures, with insufficient warm-up, with carrying bags on the shoulder, with the use of soft pillows and mattresses. Stimulator of pathological processes can act flatfoot. If the foot does not provide adequate cushioning of interactions with the support, the spinal column has to do the latter. Obesity also contributes to spinal osteochondrosis. Excess fat tissue, deposited in different places, complicates balance support and overloads intervertebral joints. Complications of osteochondrosis include such diseases as: protrusion, disc herniation (intervertebral hernia, spinal hernia), kyphosis, sciatica.

The causes of changes in the intervertebral discs are not fully understood. People begin to feel manifestations of osteochondrosis most often after 35 years. The development and exacerbation of this disease contribute to various back injuries, static and dynamic overload, as well as vibration. The older a person is, the more manifestations he has. But in recent years, more and more people aged 18 to 30 years complain of back pain. There are many reasons for the early manifestation of the disease: poor physical fitness, poor posture and spinal curvature, flatfoot and overweight. The main reasons: hereditary (genetic) predisposition; metabolic disorders in the body, infection, intoxication; overweight; improper nutrition (lack of micronutrients and fluids); age changes; spinal injuries (bruises, fractures); violation of posture, curvature of the spine, hypermobility (instability) of segments of the spinal column, flat feet; adverse environmental conditions; sedentary lifestyle; work associated with lifting weights, frequent changes in the position of the body (turns, bending and unbending, jerking movements); prolonged exposure to uncomfortable postures while standing, sitting, lying, lifting and carrying weights, while doing other work, which increases the pressure in the discs and the load on the spine as a whole; excessive exercise, uneven developed musculoskeletal system; overload of the spine associated with diseases of the foot, as well as the result of wearing uncomfortable shoes, high heels and pregnancy in women; abrupt termination of regular training by professional athletes; nervous tension, stressful situations; smoking.

Patients suffering from osteochondrosis complain of constant aching pain in the back, which is often joined by numbness and a feeling of aching limbs. In the absence of adequate treatment, weight loss and atrophy of the extremities occur. The main symptoms are: constant aching back pain, numbness and aches in the limbs; increased pain during sudden movements, physical exertion, weight lifting, coughing and sneezing; decreased movement, muscle spasms; in osteochondrosis of the cervical spine: pain in the arms, shoulders, headaches; Perhaps the development of so-called vertebral artery syndrome, which consists of the following complaints: noise in the head, dizziness, flashing "flies", colored spots before the eyes, combined with a burning, pulsating headache. The cause of vertebral artery syndrome may be its spasm in response to both direct irritation of its sympathetic plexus due to bone growth, disc herniation, arthrosis of the intervertebral joint, and reflex reaction due to irritation of any spinal receptors. The presence of vertebral artery syndrome may aggravate the course of coronary or cardiovascular disease, if present; in osteochondrosis of the thoracic spine: pain in the chest (as the "number" in the chest), in the region of the heart and other internal organs; in osteochondrosis of the lumbosacral spine: lower back pain radiating to the sacrum, lower limbs, sometimes to the pelvic organs; damage to the nerve roots (with herniated intervertebral discs, bone growths, spondylolisthesis, spondylarthrosis): shooting pain and impaired sensitivity, hypotrophy, hypotension, weakness in the innervated muscles, reduced reflexes.

The establishment of a preliminary diagnosis is carried out at 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 may manifest themselves as pain syndrome, deformity or limited mobility. The spine is examined in the position of the patient standing, sitting and lying, both at rest and in motion. The level of damage to the spine is determined by counting the number of vertebrae from certain anatomical landmarks or according to a special scheme. When viewed from the back pay attention to the posture, the structural features of the trunk, mark the line of spinous processes (median groove of the back) the lower corners of the blades, the iliac crest, the side contours of the waist and the neck position shoulder girdles deviation mezhyagodichnoy furrow from vertical reveal protrusion spinous processes, Pay attention to the relief of the muscles located near the spine. Feeling the spine allows you to supplement the inspection data (the presence or absence of deformity), to determine the location, degree and nature of pain. When palpating, muscle tension located near the spine is also noted, since most injuries and diseases of the spine are accompanied by an increase in muscle tone. Spinal flexion is used to determine the amplitude of movements in different parts of the spine. Radiography, computed tomography and magnetic resonance imaging, which determine the level of the lesion, determine the diagnosis, specify the latent pathology, determine the main role in the study of the spine. These diagnostics allow the attending physician to determine the tactics of treatment and choose the most effective methods of treatment. [URL: bp 8: //glv11are <11a.og \ U1k1 / Osteochondrosis]

Spondyloarthrosis is a particular form of osteoarthritis, which is a heterogeneous form of diseases that differ in clinical picture and outcome, based on the defeat of all components of the joint - cartilage, subchondral bone, ligaments, capsule and periarticular muscles. The most frequent localization of osteoarthritis are arthrosis of the knee and hip joints, and also the spine. In the latter case, both the joints between the vertebral bodies and the arcuate-like (faceted) joints of the vertebral segments are affected.

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

A) The early occurrence of arthrosis is promoted by such anomalies as the presence of transitional lumbosacral vertebrae; 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 occurrence of recurrent back pain) is played by the violation of articular tropism, i.e. asymmetrical arrangement of arcuatal joints.

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

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

“Transitional vertebra” - in addition to facet tropism anomalies, the change in the number of moving vertebrae at the lumbar level is most significant among the causes of pain. Lumbarization of the first sacral vertebra increases the “lever arm” for the lower back and causes an increased load on the lumbosacral articulation. Sacralisation of the fifth lumbar vertebra is unlikely to be the cause of pain if the vertebra is firmly connected to the sacrum. However, if sacralization is one-sided, the load on the vertebra becomes abnormal. The most common form of sacralization is when one is transverse. the process of the fifth lumbar vertebra is enlarged and connected to the sacrum by the joint. The axis of movement on the side of the joint is displaced 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 opposite side of sacralization.

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

"Spina bifida occulta" - refers to the cleft of the lumbar vertebrae. Anomaly is so common that it can be considered as a variant of the anatomical norm.

B) Injury is a very common cause of lower back pain. Often it is facilitated by insufficient physical condition of the individual. Most muscle sprain and lumbar pain can be prevented by controlling body weight, daily exercise and regular athletic activity (depending on age and physical condition). Athletes and young healthy people rarely damage 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 exertion, it is often excessive for them. Thus, a person sitting at a desk five days a week cannot count on a successful game of tennis.

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

Spondylolysis and spondylolisthesis are many of the stress fractures of the “isthmus” or “inter-articular segment” of the vertebra. Spondylolysis isthmus defect, spondylolisthesis is a bilateral defect with anterior slipping of the body of the affected vertebra and the transverse processes of the underlying vertebra. Thus, with spondylolisthesis, the posterior vertebrae (spinous process and arch) remain in the normal position. The degree of slipping ranges from 1st to 4th degree. 1st degree - offset from 0 to 25% and 4th - full forward displacement of the vertebra. The fifth lumbar vertebra suffers most often, followed by the fourth lumbar vertebra. In an oblique x-ray projection, the normal vertebra looks like a “spaniel in profile”. In the presence of such a "spaniel""collar" we can talk about spondylolysis; if "the dog's head is separated from the body" - there is spondylolisthesis.

Spondylolisthesis is usually not a significant problem, with irregular, occasional low back pain as the only symptom. However, in active teenagers, the problem can be more serious, especially with the progression of spondylolisthesis. Further slipping can cause severe compression of the roots and stabilization of the vertebral segments is required.

C) Vertebral instability is an independent nosological unit; the lumbar vertebra is shifted back or forward relative to the lower vertebra. It usually occurs between the third and fourth and between the fourth and fifth lumbar vertebrae. Usually offset forward and occurs when the slopes.

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

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

Under the influence of static-dynamic loads, the elastic gelatinous core of the intervertebral disk, which plays a cushioning role and ensures the flexibility of the spine, begins to lose its physiological properties due to, first of all, the depolarization of the saccharides of the nucleus. In conditions of a modified, increased mobility of the spinal segment (instability), reactive changes occur in the adjacent vertebral bodies and in the joints - spondylarthrosis associated with osteochondrosis develops.

The composition of the vertebral segment includes not only the cartilaginous disk between the adjacent vertebrae and the arcuate joints, but also the ligaments and muscles connecting them - intertransigal, inostinoid and rotator muscles. These muscles, under the influence of impulses from the affected vertebral segment, especially from the posterior longitudinal ligament, reflexively tense; their asymmetrical stress causes curvature spine - scoliosis, which doctors often observe in patients suffering from spondyloarthrosis.

The main clinical manifestation of osteoarthritis is pain that occurs when you move, change the posture of the body and passes 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 muscular-tonic reactions develop, causing pain and spinal mobility limiting, lasting several weeks or months.

The specific situation is diagnosed according to clinical criteria and radiological, in particular, computed tomographic data. [Gorbachev F.E. Spondyloarthrosis of the spine: diagnosis and treatment. M., 2007. 12 s]

The basis of degenerative dystrophic changes in arthrosis is the primary damage to the cartilage, followed by an inflammatory reaction, so arthrosis is often called arthrosis-arthritis. Arthrosis is always associated with deformation of the bone tissue, and therefore it is also called osteoarthritis or deforming arthrosis.

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

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

The tool according to the invention may additionally contain auxiliary substances. The auxiliary substances can be stearic acid, magnesium stearate and / or manganese sulfate, sodium chloride, aspartame, sorbitol, citric acid and / or carbovax 4000, calcium phosphate disubstituted, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmalloser and a sample of croscarmellostellar drawing. 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. peripheral joints, intervertebral osteochondrosis, osteoarthrosis and osteoporosis, periodontal disease and / or to accelerate the formation of callus in fractures.

The tool in the form of hard gelatin capsules of the present 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 particular, the agent of the present invention may comprise:

Diacerein 50 mg;

Chondroitin 400 mg;

Glucosamine 500 mg.

In particular, the agent of the present invention may additionally contain one or more of:

Stearic acid 10 mg;

Magnesium stearate 5 mg;

Manganese sulfate 1 mg.

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

The tool in the form of a sachet according to the present 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 particular, the agent of the present invention may comprise:

Composition N ° l:

Diacerein 50 mg;

Chondroitin 400 mg;

Glucosamine 500 mg.

Composition N ° 2:

Diacerein 100 mg;

Chondroitin 800 mg;

Glucosamine 1000 mg.

Composition H:

Diacerein 100 mg;

Chondroitin 1000 mg;

Glucosamine 1500 mg. In particular, the agent of the present invention may additionally contain one or more of: sodium chloride, aspartame, sorbitol, citric acid, carbowax 4000.

The tool in the form of tablets of the present 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 particular, the agent of the present invention may comprise:

Diacerein 50 mg;

Chondroitin 500 mg;

Glucosamine 500 mg.

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

EXAMPLES

The examples included in the present description are not limiting to the claimed invention and are given only for the purpose of illustrating and confirming the achievement of the expected technical results. These examples are among the many experimental data obtained by the authors of the invention, which confirm the effectiveness of the means for oral administration, which are within the scope of the invention.

Example 1. Obtaining a tool according to the invention and the means of comparison.

1. Get the tool And in capsules, containing:

Diacerein 50 mg;

Chondroitin 400 mg;

Glucosamine 500 mg.

2. Get the tool In capsules, containing:

Diacerein 50 mg;

Chondroitin 400 mg;

Glucosamine 500 mg. Example 2. The use of the means according to the invention and the means of comparison.

The preparations obtained in Example 1 were used to evaluate 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.

Investigated 28 patients suffering from osteoarthritis of the knee joint (14 men aged 45 to 70 years and 14 women aged 50 to 70 years).

Determining the stage of osteoarthritis according to its severity was performed in accordance with the scoring. The entire examined population showed a second radiological stage of the disease.

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

Analysis of the results of the study showed an improvement in clinical symptoms after the administration of both the agent A according to the invention and the agent B. However, in the case of agent A, this improvement took place after only 2 months and persisted after 5 months with a further beneficial effect on bone and joint symptoms. The magnitude of the pain scores on the scale in the case of the means A significantly decreased compared with the initial level, demonstrating that the means A not only increases the viscoelasticity of the synovial fluid, but also has a favorable effect on the pain symptom and the patient's quality of life.

Claims

CLAIM

1. A means for oral administration in the treatment of osteoarthritis of peripheral joints, intervertebral osteochondrosis, osteoarthrosis and osteoporosis, periodontal disease and / or to accelerate the formation of callus in fractures containing diacerein, chondroitin and glucosamine.

2. Means under item 1, characterized in that it is a capsule.

3. Means under item 1, characterized in that it is a sachet.

4. Means under item 1, characterized in that it is a tablet.

5. Tool 2, characterized in that it further contains auxiliary substances.

6. A means of 5, characterized in that the excipients are stearic acid, magnesium stearate and / or manganese sulfate.

7. Tool 3, characterized in that it further contains auxiliary substances.

8. Means on 7, characterized in that the excipients are sodium chloride, aspartame, sorbitol, citric acid and / or carbowax 4000.

9. Means for 4, characterized in that it further contains auxiliary substances.

10. A product according to claim 9, wherein the excipients are disubstituted calcium phosphate, microcrystalline cellulose, magnesium stearate, stearic acid, croscarmellose sodium, hydroxypropylmethylcellulose, titanium dioxide (E171) and / or triacetin.

11. Means under item 1, characterized in that it contains:

Diacerein, from about 10 to about 200 mg;

Chondroitin from about 200 to about 1000 mg;

Glucosamine from about 200 to about 1000 mg.

12. The use of tools according to any one of paragraphs. 1-11 for the treatment of osteoarthritis of peripheral joints, intervertebral osteochondrosis, osteoarthritis and osteoporosis, periodontal disease and / or to accelerate the formation of callus in fractures.