Pharmaceutical agent for treating joint diseases

Abstract

The invention relates to the field of medicine, and more particularly to medicinal agents for treating joint diseases. An agent for treating joint diseases includes an effective amount of chondroitin sodium sulphate and at least one adjuvant or carrier, and further contains iron in a relative amount of from 1 mg / kg to 40 mg / kg, calculated on the basis of the mass of chondroitin sodium sulphate.

Description

[0001] PHARMACEUTICAL PRODUCT FOR TREATMENT

[0002] ARTHROLOGICAL DISEASES

[0003] FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

[0004] The invention relates to the field of medicine, in particular to medicinal products for the treatment of arthrological diseases.

[0005] LEVEL OF TECHNOLOGY

[0006] According to the World Health Organization, musculoskeletal diseases are the leading cause of disability worldwide. Such diseases limit mobility and motor skills, leading to premature termination of work activity, reducing the ability to perform social functions.

[0007] Degenerative joint disease or osteoarthritis (OA) is the most common form of joint disease, with the knee joint most commonly affected. More than four million new patients seek medical attention each year because of knee pain. An estimated 10% of the population over 55 years of age have signs of knee dysfunction, with about 25% of these having serious problems that affect the patient’s quality of life. According to the WHO Global Burden of Disease report, knee OA is one of the leading causes of disability: the fourth leading cause in women and the eighth leading cause in men. Osteoarthritis can affect anyone, regardless of gender, age, race, or skin colour. The main manifestations of OA are the disruption of the structure of articular cartilage, remodelling of the subchondral bone, and the formation of osteophytes (ossification of the joints).The course of the disease is chronic, progressive, exacerbation most often occurs under the influence of mechanical factors, destructive changes progressively increase. OA occurs not only in old age, but also in the working population, often leading to a decrease in mobility, up to disability, the socio-economic price of which is very high. The appearance of OA is closely related to age: up to 50 years, the disease is more common in men, after 50 years in women, which is the result of a lack of estrogens during menopause. At the same time, the frequency of the disease in women and men becomes the same at about 80 years of age.

[0008] The basis for maintaining joint function is chondromodulating therapy, which today widely uses drugs based on sodium salt of chondroitin sulfate - a mucopolysaccharide obtained from animal tissues. The drug effectively affects metabolic processes in the patient's connective tissue, including cartilage, stimulating and normalizing the biosynthesis of glycosaminoglycans.

[0009] Chondroitin sulfate (CS) is a high-molecular heteropolysaccharide that belongs to the group of glycosaminoglycans, linear unbranched polymers.

[0010] The structure of the CS molecule determines its polyanionic properties and participation in the processes of transport of water, amino acids and lipids in avascular areas of cartilage. Long chains of CS, which are part of the extracellular matrix, determine the most important biomechanical properties of cartilage tissue. CS is a structural modulator that is not only synthesized by the body, but also after administration integrates into the structures of cartilage tissue, stimulating its synthesis and inhibiting destruction. Its timely administration and regular use ensure inhibition, stabilization and prevention of the development of destructive processes in the joint. The main function of CS in the body is to retain water and nutrients in the cartilage and ensure the movement of molecules through the cartilage tissue. This is an essential property, since there is no blood in the cartilage to ensure metabolism. CS is also a chondroprotector.The water it retains in the thickness of the cartilage creates good cushioning and absorbs shock, which ultimately increases the strength of the connective tissue.

[0011] HS is a natural component of articular cartilage, playing an important role in maintaining the necessary osmotic pressure, due to which the matrix and collagen threads stretch. This substance has anti-inflammatory activity, affecting mainly the cellular component of inflammation, stimulates the synthesis of hyaluronic acid and proteoglycans, and inhibits the action of proteolytic enzymes.

[0012] Chondroitin sulfate preparations

[0013] There are currently a significant number of drugs with HS on the market. They are divided into three main groups:

[0014] 1. Topical agents. 2. Oral agents.

[0015] 3. Parenteral agents.

[0016] The 1st group includes:

[0017] The medicinal product "Chondroitin AKOS ointment". It is used externally. Apply 2-3 times a day to the skin above the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, the course of treatment is repeated.

[0018] The medicinal product "Chondroitin ointment". It is used externally. Apply 2-3 times a day to the skin over the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, the course of treatment is repeated.

[0019] The medicinal product "Osteoregin ointment". It is used externally. Apply 2-3 times a day to the skin above the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, the course of treatment is repeated.

[0020] The medicinal product "Ambene Chondro gel". It is used externally. Apply 2-3 times a day to the skin over the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is from 2-3 weeks to 2-3 months. If necessary, the course of treatment is repeated.

[0021] The medicinal product "Sustamhondro ointment". It is used externally. Apply 2-3 times a day to the skin over the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is from 2-3 weeks to 2-3 months. If necessary, the course of treatment is repeated.

[0022] The medicinal product "Artravir Trivium ointment". It is used externally. Apply 2-3 times a day to the skin over the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, the course of treatment is repeated after consulting a doctor.

[0023] The medicinal product "Artrafik ointment". It is used externally. Apply 2-3 times a day to the skin over the lesion and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, the course of treatment is repeated after consulting a doctor.

[0024] The medicinal product "Chondroglyuksid gel". It is used externally. The gel is applied 2-3 times a day in a thin layer of a 4 cm strip (2 g) to the intact skin over the affected area, then rubbed in until absorbed for 2-3 minutes. The duration of use of the drug is 1 month. A repeated course may be recommended by a doctor. The main problem with topical agents is their low bioavailability and short duration of therapeutic action. In this regard, topical agents are often used in conjunction with parenteral agents. With monotherapy, patients are often forced to use repeated courses, while the therapeutic effectiveness of such courses is low.

[0025] The 2nd group includes:

[0026] The drug "Structum". The drug is for oral administration. Take 1 capsule (500 mg) 2 times a day. The recommended course of treatment is 6 months.

[0027] The drug "Ambene Chondro". The drug is for oral administration. Prescribed 2 capsules (250 mg) 2 times a day or 1 capsule (500 mg) 2 times a day. The recommended course of treatment is 6 months.

[0028] The medicinal product "Chondroitin Velpharm". The drug is for oral administration. Prescribed 1 g (2 capsules of 250 mg or 1 capsule of 500 mg) 2 times a day. The recommended course of treatment is 6 months.

[0029] The drug "Artrafik". The drug is for oral administration. Prescribed 1 g / day, 500 mg 2 times / day or 2 capsules 250 mg 2 times / day. The recommended course of treatment is 6 months.

[0030] The medicinal product "ARTRAVIR®-TRIVIUM®". The drug is for oral administration. Prescribed at 1 g per day - 2 capsules of 250 mg or 1 capsule of 500 mg 2 times a day. The recommended duration of the initial course of treatment is 6 months.

[0031] The medicinal product "Chondroitin-AKOS". Capsules. The drug is for oral administration. Prescribed at 1 g per day - 2 capsules 2 times a day. The recommended duration of the initial course of treatment is 6 months.

[0032] The medicinal product "Chondroitin-VERTEX". Capsules. Prescribed at 1 g per day - 2 capsules 2 times a day. The recommended duration of the initial course of treatment is 6 months.

[0033] The medicinal product "Chondroxide". Tablets. Taken orally 0.5 g (2 tablets) 2 times a day. The recommended duration of the initial course of treatment is 6 months.

[0034] Also known are complex preparations produced in the form of tablets and capsules containing chondroitin sulfate and glucosamine. Such preparations include "Artra" (tablets), "Artravir - Trivium complex" (capsules), Artrafik Pro (capsules), Tazan (tablets). These preparations have a complex effect due to the presence of two active substances in the composition. However, the course of treatment is similar to the course of preparations with one active substance and should be at least 6 months. Repeated courses are also necessary.

[0035] Thus, oral agents, as well as preparations in the form of ointments and gels, have low bioavailability. According to various literary sources, it is from 8 to 13%. Also, they often use a low-quality substance. These products are recommended for use as a preventive measure. The course of treatment when using such products is characterized by a long duration (at least 6 months), high cost and short duration of action: repeated courses are necessary, since after completing the full course, the effect of the drugs lasts no more than 3 months.

[0036] The 3rd group includes:

[0037] The medicinal product "Mukosat solution for intramuscular and intra-articular administration". The drug is administered intramuscularly, 1 ml every other day. If well tolerated, the dose is increased to 2 ml, starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, repeated courses can be carried out after 6 months. For the formation of bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0038] The medicinal product "Artogistan solution for intramuscular injection". It is used intramuscularly, 100 mg every other day. If well tolerated, the dose is increased to 200 mg, starting with the fourth injection. The course of treatment is 25-35 injections. If necessary, a repeat course of treatment can be carried out after 6 months.

[0039] The medicinal product "Chondrogard solution for intramuscular and intra-articular administration". It is used intramuscularly, 100 mg every other day. If well tolerated, the dose is increased to 200 mg, starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, a repeat course of treatment can be carried out after 6 months. In case of osteoarthritis of large joints, a combination of intra-articular and intramuscular administration methods is possible. Up to 5 intra-articular injections of 200 mg are carried out with a 3-day break between injections and 16 intramuscular injections of 200 mg with a 1-day interval between injections (every other day). Depending on the size of the joint, up to 2 ml of the drug "Chondrogard" can be injected into the joint cavity.

[0040] The medicinal product "Injectran solution for intramuscular and intra-articular administration". It is used intramuscularly, 1 ml every other day. If well tolerated, the dose is increased to 2 ml, starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, a repeat course of treatment can be carried out after 6 months. In case of osteoarthritis of large joints, a combination of intra-articular and intramuscular administration methods is possible. Up to 5 intra-articular injections of 2 ml are carried out with a 3-day break between injections and 16 intramuscular injections of 2 mg with a 1-day interval between injections (every other day). Depending on the size of the joint, up to 2 ml of the drug "Injectran" can be injected into the joint cavity.

[0041] The medicinal product "Mucosat solution for intramuscular and intraarticular administration". The drug is administered intramuscularly at 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, repeated courses can be carried out after 6 months.

[0042] To form bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0043] In osteoarthrosis of large joints, a combination of intra-articular and intramuscular administration methods is possible. Up to 5 intra-articular injections of 200 mg are administered with a 3-day interval between injections and 16 intramuscular injections of 200 mg with a 1-day interval between injections (every other day).

[0044] Intra-articular administration of the drug is carried out under aseptic conditions by a specialist trained in the technique of intra-articular administration. Depending on the size of the joint, up to 2 ml of the drug Mucosat can be injected into the joint cavity.

[0045] After intra-articular administration of the drug, the puncture site is lubricated with an alcohol wipe and a bactericidal plaster is applied.

[0046] The medicinal product "Chondroitin-Apex solution for intramuscular injection". Intramuscularly, 1 ml every other day. If well tolerated, the dose is increased to 2 ml, starting with the 4th injection. The course of treatment is 25-30 injections. If necessary, a repeated course of treatment can be carried out after 6 months. The duration of repeated courses of treatment is determined by the doctor. For the formation of bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0047] The medicinal product "Chondroitin-B solution for intramuscular injection". Intramuscularly, 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-35 injections. If necessary, a repeated course of treatment can be carried out after 6 months. The duration of repeated courses of treatment is determined by the doctor. For the formation of bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0048] The medicinal product "Chondroitin-Binergia solution for intramuscular and intraarticular administration". The drug is administered intramuscularly at 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-35 injections. If necessary, a repeat course of treatment can be administered after 6 months.

[0049] In osteoarthrosis of large joints, a combination of intra-articular and intramuscular administration methods is possible. Up to 5 joint injections of 2 ml are administered with a 3-day interval between injections and 16 intramuscular injections of 2 ml with a 1-day interval between injections (every other day).

[0050] Intra-articular administration of the drug is carried out under aseptic conditions by a specialist trained in the technique of intra-articular administration. Depending on the size of the joint, up to 2 ml of the drug can be injected into the joint cavity.

[0051] After intra-articular administration of the drug, the puncture site is lubricated with an alcohol wipe and a bactericidal plaster is applied.

[0052] To form a bone callus, the course of treatment is 3-4 weeks (10-14 intramuscular injections every other day).

[0053] The medicinal product "Chondroitin sulfate solution for intramuscular injection". The drug is administered intramuscularly at 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, repeated courses can be carried out after 6 months.

[0054] To form bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0055] The medicinal product "Chondrofast solution for intramuscular injection". The drug is administered intramuscularly at 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, repeated courses can be carried out after 6 months.

[0056] To accelerate the formation of bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0057] The medicinal product "Khonsat solution for intramuscular injection". The drug is administered intramuscularly at 1 ml (100 mg) every other day. If well tolerated, the dose is increased to 2 ml (200 mg), starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, repeated courses can be carried out after 6 months.

[0058] To form bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0059] The medicinal product "Chondromed-Lekpharm solution for intramuscular injection" The medicinal product is administered intramuscularly at 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-35 injections. If necessary, a repeat course of treatment can be administered after 6 months.

[0060] The medicinal product "ARTRAVIR-TRIVIUM solution for intramuscular injection". Administer intramuscularly 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), starting with the fourth injection. The course of treatment is 25-30 injections. If necessary, repeat courses can be carried out after 6 months.

[0061] Parenteral preparations of sodium chondroitin sulfate are the most effective. This is due to high bioavailability. After intramuscular injection, sodium chondroitin sulfate is detected in the synovial fluid after 15 minutes, then it enters the joint, where it reaches its maximum after 48 hours.

[0062] The disadvantages of such drugs include similar side effects - allergic reactions (skin itching, erythema, urticaria, dermatitis, edema), hemorrhages at the injection site. And since the above drugs have a long course of treatment (at least 25 injections), this inevitably leads to an increase in the number of these side effects. In addition, long courses are not convenient for patients, since it is necessary to visit treatment rooms for at least 25 days, not all medical specialists are trained to do these injections, especially intra-articular ones. This leads to the fact that patients do not undergo full courses of treatment, significantly reducing the effectiveness of the treatment. Also, for all the listed drugs, repeated courses are required at least 6 times a year, which also creates difficulties for patients or leads to reluctance to continue further treatment.

[0063] Use of iron

[0064] The role of iron in metabolism

[0065] Iron helps support many important functions of the body, affecting the level of vital energy, concentration, gastrointestinal processes, the immune system and the regulation of body temperature. Its deficiency or excess immediately affects well-being. Iron is an important component of hemoglobin, which consists of red blood cells (erythrocytes). Hemoglobin contains about two-thirds of the iron in the body. It combines with oxygen, and red blood cells carry it from the lungs throughout the body. This mineral is also a part of many elements responsible for cholesterol metabolism, the processing of calories into energy, the fight against toxins, and is involved in the process of stopping inflammatory processes. Thanks to iron, the immune system copes with its functions better, and red blood cells with its help send carbon dioxide to the lungs for processing. It is also necessary for maintaining the health of cells, skin, hair and nails.Iron metabolism disorders can have various clinical manifestations, including anemia (a decrease in the concentration of hemoglobin and / or the number of red blood cells in the blood) and hemochromatosis (a hereditary disease that leads to the accumulation of iron in tissues). Iron in the human body is a component of many enzymes and proteins that are necessary for metabolic processes - the destruction and utilization of toxins, cholesterol metabolism, and the conversion of calories into energy. It also helps the body's immune system cope with aggressors. A dose of elemental iron not exceeding 20 mg / kg of weight is non-toxic, from 20 to 60 mg / kg of weight is slightly and moderately toxic, and > 60 mg / kg of weight can cause symptoms of severe poisoning. Various iron compounds are used in medicine. For example, ferrous sulfate, ferrous fumarate, ferrous hydroxide, ferrous gluconate, ferric pyrophosphate and others. All iron compounds are well known to specialists and are commercially available.

[0066] Iron containing products

[0067] Currently, there are a large number of drugs that contain iron in the form of various chemical compounds.

[0068] "Ferrovit" tablets. Vitamin and mineral complex. Contains iron in the form of iron sulfate, folic acid and vitamin B 12. Used as a preventive measure for conditions accompanied by an increased need for vitamins and iron.

[0069] "Ferroplex" dragee. Contains iron in the form of iron sulfate, vitamins B 12, C and folic acid. Used to treat and prevent iron deficiency anemia.

[0070] "Ferroglobin" capsules. Contains iron in the form of ferrous fumarate, folic acid and vitamins B6 and B 12. Prescribed for: iron-, folate- and B 12-deficiency anemia caused by prolonged bleeding (including blood loss due to surgery); diets and impaired absorption of iron from the gastrointestinal tract; to improve physical development;

[0071] "Maltofer" tablets. Contains iron hydroxide. Used to treat anemia caused by iron deficiency, as well as to prevent iron deficiency.

[0072] "Totema" solution for oral administration. Contains iron gluconate dihydrate, manganese, copper. Used for the prevention and treatment of iron deficiency anemia.

[0073] "Sideral Forte" capsules. Contains iron pyrophosphate. Used as a dietary supplement as prescribed by a doctor for various iron deficiency conditions.

[0074] "Ferrum Lek" solution for intramuscular injection. Contains iron hydroxide. Used to treat anemia.

[0075] "Sorbifer Durules" tablets. Contains iron sulfate and ascorbic acid. Used to treat iron deficiency anemia.

[0076] All of the above mentioned remedies are intended for the treatment and prevention of iron deficiency conditions.

[0077] DISCLOSURE OF THE ESSENCE OF THE INVENTION

[0078] The objective of the present invention is to eliminate the disadvantages inherent in the known sodium chondroitin sulfate agents described above.

[0079] The objective of the present invention is to develop a product with sodium chondroitin sulfate in the form of solid, soft and liquid forms for the treatment of arthrological diseases, containing essential fatty acids and possessing high efficiency, which include the active substance - sodium chondroitin sulfate.

[0080] The set tasks are solved by creating a means for treating arthrological diseases, including an effective amount of sodium chondroitin sulfate and at least one auxiliary substance or carrier, characterized in that it additionally contains iron in a relative amount from 1 mg / kg to 40 mg / kg, based on the mass of the active substance - sodium chondroitin sulfate.

[0081] The technical result of the present invention consists in high efficiency of the agent, high regeneration and acceleration of growth of cartilaginous tissue and increase in cartilage thickness. It has been revealed that introduction of a certain amount of iron into the compositions including sodium chondroitin sulfate leads to reduction of the course of treatment, increase in the rate of regeneration of cartilaginous tissue and reduction of side effects.

[0082] The use of the agent according to the invention leads to the normalization of metabolic processes, acceleration of the removal of edemas in case of injuries and / or injections and a high process of tissue regeneration in the area of ​​injury and / or injection, and improvement of tissue blood supply.

[0083] In the context of the present invention, iron is understood to mean elemental (atomic) iron in divalent or trivalent form as part of various chemical compounds used for the manufacture of medicines and biologically active additives.

[0084] The choice of a specific iron compound is determined by the specific dosage form.

[0085] In the context of the present invention, iron salts or their solutions in a pharmaceutically acceptable solvent can be used, for example, iron sulfate, iron fumarate, iron hydroxide, iron gluconate, iron pyrophosphate. This list is not exhaustive. These salts are well known and commercially available.

[0086] The amount of iron compound used in the composition of the product is determined by the required amount of iron per kg of sodium chondroitin sulfate and can be calculated by a specialist.

[0087] The agent according to the present invention includes iron in a relative amount from 1 mg / kg to 40 mg / kg based on the weight of the active substance - sodium chondroitin sulfate.

[0088] In a particular embodiment, in a relative amount of 2 mg / kg to 20 mg / kg, as well as 1 mg / kg to 18 mg / kg, as well as 1 mg / kg to 16 mg / kg, as well as 3 mg / kg to 30 mg / kg, as well as 10 mg / kg to 32 mg / kg, as well as 10 mg / kg to 35 mg / kg, as well as 17 mg / kg to 37 mg / kg, as well as 4 mg / kg to 28 mg / kg, from 1 mg / kg to 6 mg / kg, as well as 1 mg / kg to 8 mg / kg, as well as 2 mg / kg to 9 mg / kg, as well as 3 mg / kg to 10 mg / kg, as well as 5 mg / kg to 12 mg / kg, as well as 9 mg / kg to 15 mg / kg, as well as 6 mg / kg to 11 mg / kg, and also from 2 mg / kg to 7 mg / kg, and also from 8 mg / kg to 13 mg / kg, and also from 10 mg / kg to 18 mg / kg, and also from 15 mg / kg to 20 mg / kg, and also from 20 mg / kg to 27 mg / kg, and also from 25 mg / kg to 35 mg / kg based on the mass of the active substance.

[0089] The proposed iron concentrations are suitable for solving the tasks set. The claimed product includes an effective amount of sodium chondroitin sulfate. An effective amount is understood as an amount that has a therapeutic effect.

[0090] The therapeutic amount of sodium chondroitin sulfate in the claimed product corresponds to the amounts of sodium chondroitin sulfate in known products of the same purpose.

[0091] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 50 mg to 2500 mg.

[0092] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 100 mg to 2000 mg.

[0093] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 300 mg to 1500 mg.

[0094] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 500 mg to 1200 mg.

[0095] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 50 mg to 250 mg.

[0096] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 50 mg to 150 mg.

[0097] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 100 mg to 500 mg.

[0098] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 150 mg to 400 mg.

[0099] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 600 mg to 1400 mg.

[0100] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 750 mg to 1850 mg.

[0101] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 850 mg to 1650 mg.

[0102] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 900 mg to 1900 mg.

[0103] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 1000 mg to 2200 mg.

[0104] In a particular embodiment, the amount of sodium chondroitin sulfate in the product may be from 250 mg to 1000 mg. In a particular embodiment, the amount of sodium chondroitin sulfate in the product may be from 500 mg to 800 mg.

[0105] In a particular case, the amount of sodium chondroitin sulfate in the product can range from 400 mg to 900 mg.

[0106] Forms of release of the invention

[0107] The statements made in this section are not limiting and merely illustrate specific embodiments of the invention.

[0108] The agent according to the present invention can be made in solid, soft or liquid form.

[0109] The product can be used orally, by injection or locally.

[0110] Soft forms intended for topical use include creams, gels, and ointments.

[0111] Oral forms include tablets and capsules.

[0112] Injectable forms include lyophilisates and injection solutions.

[0113] Auxiliary components are selected depending on the form of manufacture and can be easily selected by specialists.

[0114] A product made in the form of a cream, gel or ointment may contain one or more essential oils selected from the group: dimethyl sulfoxide, propylene glycol, carbomer, trolamine, macrogol, edetate, neroli and lavender oils, lanolin, petrolatum.

[0115] The product, made in the form of a tablet, may additionally contain glucosamine hydrochloride. The mass ratio of glucosamine hydrochloride to sodium chondroitin sulfate may be 0.5 - 5: 1.

[0116] In a particular embodiment, the ratio of sodium chondroitin sulfate to glucosamine hydrochloride in the tablet is 1:1.

[0117] The tablet may additionally contain the following excipients, taken in relation to sodium chondroitin sulfate: calcium sulfate dibasic - 1:0.46, microcrystalline cellulose - 1:0.37 mg, sodium croscarmellose - 1:0.16, stearic acid - 1:0.14, magnesium stearate - 1:0.02.

[0118] In a particular embodiment, the tablet may be film-coated, in which case the tablet coating has the following composition, taken in relation to sodium chondroitin sulfate: hydroxypropyl methylcellulose - 1:0.07, titanium dioxide (E171) - 1:0.016, triacetin - 1:0.014 mg.

[0119] The product, made in the form of a capsule, may additionally contain auxiliary substances selected from the group: talc, stearic acid, magnesium stearate, manganese sulfate.

[0120] The capsule shell composition may include titanium dioxide and gelatin.

[0121] The product, which is made in the form of a solution, contains water.

[0122] More specifically, the product contains distilled water, injection water or apyrogenic water.

[0123] The finished parenteral product may contain a certain amount of preservatives such as benzyl alcohol, sodium benzoate, sodium metabisulfite, sodium bisulfite, methyl parahydroxybenzoate or similar.

[0124] Therapeutic efficacy

[0125] The claimed product is intended for the treatment of arthrological diseases.

[0126] The dosage and daily dose of sodium chondroitin sulfate depends on the form of the drug.

[0127] For injection and lyophilized products, the dosage is 100 mg / ml sodium chondroitin sulfate, the daily dose is 200 mg. It is administered intramuscularly every other day.

[0128] For tablets and capsules, the dosage of sodium chondroitin sulfate is 500 mg. The daily dose is 1000 mg. It is used orally, 2-3 capsules / tablets per day.

[0129] For ointments and gels, the dosage of sodium chondroitin sulfate is 5.0 g per 100 g. It is used by applying it externally to the affected joints 2-3 times a day.

[0130] These diseases include degenerative-dystrophic diseases of the joints and spine: osteoarthrosis of the peripheral joints, intervertebral osteochondrosis and osteoarthrosis, rheumatoid arthritis, gout, reactive arthritis, spondyloarthropathies, arthritis in systemic lupus erythematosus, dermatomyositis and other systemic diseases, psoriatic arthritis, post-traumatic injuries of articular cartilage, ligaments, menisci. BRIEF DESCRIPTION OF DRAWINGS

[0131] Fig. 1 - Graph of changes in the thickness of articular cartilage in animals of Group No. 1 (G1).

[0132] Fig. 2 - Graph of changes in the thickness of articular cartilage in animals of Group No. 2 (G2).

[0133] Fig. 3 - Graph of changes in the thickness of articular cartilage in animals of Group No. 3 (G3).

[0134] Fig. 4 - Graph of changes in the thickness of articular cartilage in animals of Group No. 4 (G4).

[0135] Fig. 5 - Graph of changes in the thickness of articular cartilage in animals of Group No. 5 (G5).

[0136] Fig. 6 - Graph of changes in the thickness of articular cartilage in animals of Group No. 6 (Gb).

[0137] IMPLEMENTATION OF THE INVENTION

[0138] Examples of preparation of various formulations with sodium chondroitin sulfate and iron, which are not exhaustive.

[0139] Example 1. Preparation of gel

[0140] A preparation in the form of a gel, including sodium chondroitin sulfate, purified water, and which additionally contains iron in a relative amount of 1 mg / kg to 40 mg / kg based on the weight of sodium chondroitin sulfate, can be obtained using various auxiliary substances.

[0141] Option 1:

[0142] 100 kg of the preparation in the form of a gel are obtained by first preparing solution No. 1: 1200 g of carbomer from the total mass is stirred and added to 8 l of purified water. Then solution No. 2 is prepared: dissolving 39.98 g of methyl parahydroxybenzoate in 8 l of ethanol. To obtain solution No. 3, the following are mixed in 72.51 l of purified water, heated to a temperature of 65-75 °C: sodium chondroitin sulfate - 2 kg, dimethyl sulfoxide - 3 kg; propylene glycol - 3 kg; trolamine - 1200 g; carbomer - 799.52 g; macrogol glyceryl hydroxystearate - 159.90 g; Disodium edetate - 39.98 g, 1% iron gluconate solution - 3.22 ml (in terms of containing 2 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lomani GmbH, Germany). After which the solutions are mixed until a gel mass is formed. Flavors are added (wt / vol%): lavender oil - 39.98 g; orange blossom oil (neroli oil) - 19.99 g.

[0143] Option 2:

[0144] 100 kg of the preparation in the form of a gel are obtained by first preparing solution No. 1: 1232.54 g of carbomer is stirred and added to 8.22 l of purified water. Then solution No. 2 is prepared: 41.08 g of nipagin is dissolved in 6.16 l of ethanol. To obtain solution No. 3, the following are mixed in 74.60 l of purified water heated to a temperature of 65-75 °C: sodium chondroitin sulfate - 2.05 kg, dimethyl sulfoxide - 3.08 kg; propylene glycol - 3.08 kg; triethanolamine - 1233 g; macrogol - 164.34 g; disodium edetate - 61.63 g; 1% iron gluconate solution - 13.25 ml (in terms of containing 8 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lohmann GmbH, Germany). After which solutions 1, 2, 3 are mixed until a gel mass is formed. Flavors are added: lavender oil 41.08 g; orange blossom oil (neroli oil) - 20.54 g.

[0145] Option 3:

[0146] To prepare 100 kg of the preparation, solution No. 1 is obtained by adding 749.58 g of carbomer to 35.98 l of purified water and then mixing. Then, solution No. 2 is prepared by dissolving 29.98 g of methyl parahydroxybenzoate in 4497.48 ml of ethanol. Solution No. 3 is obtained by stirring while heating to a temperature of 70 °C in 54.52 l of purified water, 1500 g of sodium chondroitin sulfate, 149.92 g of glucosamine hydrochloride, 299.83 g of methylsulfonylmethane, 3 g of sodium metabisulfite, 1500 g of propylene glycol, carbomer - 749.58 g, 1% solution of iron gluconate - 12.10 ml (in terms of containing 10 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lohmann GmbH, Germany). After which the solutions are stirred for several hours until a gel mass is formed. If necessary, add a fragrance in the amount of 14.99 g.

[0147] Example 2. Preparation of ointment

[0148] A preparation in the form of an ointment, including sodium chondroitin sulfate, purified water, and which additionally contains iron in a relative amount of 1 mg / kg to 40 mg / kg based on the weight of sodium chondroitin sulfate, can also be obtained using various methods.

[0149] Option 1:

[0150] 35.71 kg of medical vaseline, 15.31 kg of anhydrous lanolin, 3.06 kg of stearic acid, 5.10 kg of pentol are melted at a temperature of (70±2)°C. Then mixed, then cooled to a temperature of (55±2)°C (ointment base). 5.10 kg of sodium chondroitin sulfate are dissolved in 25.46 l of distilled water. 10% dimethyl sulfoxide is prepared and mixed with a solution of sodium chondroitin sulfate. 45.26 ml of 1% iron gluconate solution (based on containing 11 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lohmani GmbH, Germany) are added to the solution of sodium chondroitin sulfate and dimethyl sulfoxide with stirring. The resulting substance is added to the ointment base, brought to 100 kg with water, homogenized, and then transferred for packaging.

[0151] Option 2:

[0152] Vaseline medical in the amount of 35.71 kg, anhydrous lanolin in the amount of 15.31 kg, stearic acid in the amount of 3.06 kg, pentol in the amount of 5.10 kg are melted at a temperature of (70 ± 2) ° C, stirred, then cooled to a temperature of (55 ± 2) ° C (ointment base). Sodium chondroitin sulfate in the amount of 5.10 kg is dissolved in 20.35 l of distilled water. Sodium diclofenac in the amount of 5.10 kg is dissolved in 10.20 l of dimethyl sulfoxide. 61.72 ml of 1% iron gluconate solution (containing 15 mg of elemental iron per 1 kg of sodium chondroitin sulfate, manufacturer of the substance Dr. Paul Lomani GmbH, Germany) are added to solutions of sodium diclofenac in dimethyl sulfoxide and chondroitin sulfate in water with stirring. The resulting substance is added to the ointment base, brought to 100 kg with purified water, homogenized, and then transferred for packaging.

[0153] Option 3:

[0154] To prepare 100 kg of ointment, first prepare the ointment base by adding 40.20 kg of petroleum jelly, 3.02 kg of stearic acid and 20.10 kg of lanolin to the mixer. Heat the mixture to 60-65 °C and stir until smooth. Add 15.03 g of dimethyl sulfoxide in small portions during mixing. Dissolve 1.51 kg of sodium chondroitin sulfate in 20.1 l of purified water. Add 48.63 ml of 1% ferrous gluconate solution to the solution while stirring (containing 40 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Substance manufacturer Dr. Paul Lohmani GmbH, Germany). Add the resulting solution to the ointment base, bring to 100 kg with purified water and stir until completely homogenized.

[0155] Example 3. Preparation of lyophilisate

[0156] The preparation contains 95-120 mg of lyophilized powder of Na-salt of chondroitin sulfate, which is obtained from sodium salt of chondroitin sulfate dissolved in apyrogenic injection water and iron from 1 mg / kg to 40 mg / kg based on the weight of sodium chondroitin sulfate.

[0157] The injection solution prepared from the specified lyophilisate using apyrogenic water contains Na-salt of chondroitin sulfate in a therapeutic dosage of 9.0-11.5 wt.%.

[0158] The drug can be obtained, for example, in the following way:

[0159] Option 1:

[0160] 10.2 kg of the substance containing 90-115% sodium chondroitin sulfate are dissolved in 89.77 l of apyrogenic injection water, 30 g of sodium disulfite are added with stirring. The pH is adjusted from 6.0 to 7.5 with a sodium hydroxide solution, after which 141.67 mg of iron gluconate dihydrate are added (in terms of containing 1 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance is manufactured by Pfizer Inc., Germany). Sterilizing filtration is carried out, the substance is poured into 1 mmol ampoules and sublimation is carried out in a known manner, the ampoules with the lyophilized drug are sealed.

[0161] Option 2:

[0162] 10.4 kg of the substance containing 90-115% sodium chondroitin sulfate are dissolved in 89.57 l of apyrogenic injection water, 30 g of sodium disulfite are added with stirring. The pH is adjusted from 6.0 to 7.5 with a sodium hydroxide solution, after which 722.19 mg of iron gluconate dihydrate are added (in terms of containing 5 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance is manufactured by Novartis AG. Switzerland). Sterilizing filtration is carried out, the substance is poured into 1 mmol ampoules and sublimation is carried out in a known manner, the ampoules with the lyophilized drug are sealed.

[0163] Option 3:

[0164] 10.3 kg of the substance containing 90-115% sodium chondroitin sulfate are dissolved in 89.67 l of apyrogenic injection water, 30 g of sodium disulfite are added with stirring. The pH is adjusted from 6.0 to 7.5 with a sodium hydroxide solution, after which 1144.37 mg of iron gluconate dihydrate are added (in terms of containing 8 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance is manufactured by Novartis AG. Switzerland). Sterilizing filtration is carried out, the substance is poured into 1 mmol ampoules and sublimation is carried out in a known manner, the ampoules with the lyophilized drug are sealed.

[0165] Example 4. Preparation of solution

[0166] A preparation in the form of a solution, including sodium chondroitin sulfate, purified water, and which additionally contains iron from 1 mg / kg to 40 mg / kg based on the weight of sodium chondroitin sulfate, can be obtained by the following methods.

[0167] Option 1:

[0168] Preparation of solution "A". In 52.08 l of injection water heated to 50 °C, dissolve 10.42 kg of sodium chondroitin sulfate (based on the content of the main substance). After complete dissolution of the chondroitin sulfate, cool the solution to a temperature no higher than 35 °C.

[0169] Preparation of solution "B". Add 36.46 l of injection water to 937.5 g of benzyl alcohol and stir until the benzyl alcohol is completely dissolved, add 104.17 g of sodium disulfite and 578.7 mg of iron gluconate dihydrate (in terms of containing 4 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance is manufactured by Novartis AG, Switzerland).

[0170] Preparation of solution "G". 35 l of solution "B", 0.1 M NaOH solution to pH 6-6.5 and injection water to a volume of 100 l are added to solution "A" with constant stirring. The content of the main substances and the pH of the solution are analyzed; if necessary, the solution is adjusted. Solution "G" is subjected to sterilizing filtration into a sterile container. The solution is poured into 1.0 ml ampoules and sealed.

[0171] Option 2:

[0172] Preparation of solution "A". 10 kg of sodium chondroitin sulfate (calculated as absolutely dry substance) are dissolved in 40 l of injection water heated to 50 °C. After complete dissolution of sodium chondroitin sulfate, the solution is cooled to room temperature, the volume of the solution is brought to 40 l with injection water and it is subjected to sterilizing filtration.

[0173] Preparation of solution "B". Add 25 liters of injection water to 1000 g of benzyl alcohol and stir until the benzyl alcohol is completely dissolved. Then, while stirring, add 1111.11 mg of iron gluconate dihydrate (containing 8 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance is manufactured by Pfizer Inc., Germany).

[0174] Preparation of solution “B”. 0.05 g of sodium hydroxide is dissolved in 24 l of water for injection.

[0175] Preparation of solution "G". 50 l of solution "B" are sterilely filtered into sterile solution "A" with constant stirring, and then 15-20 minutes after adding solution "B", continuing to stir the solution, 25 l of solution "B" are sterilely filtered. Stirring after adding solution "B" is continued for 15-20 minutes.

[0176] Obtaining the preparation. The missing amount (up to 100 l) of injection water is added to a sterile container with solution "G" through a sterilizing filter.

[0177] Pouring the drug solution. The solution is poured into 1 ml ampoules. The ampoules are sealed.

[0178] Option 3:

[0179] 90.7 l of water for injection at a temperature of 24 °C are loaded into a pre-prepared reactor. The water is bubbled with sterile nitrogen at an excess pressure of 0.2±0.1 bar (0.02±0.01 MPa) for at least 10 minutes (then the process is carried out with constant bubbling of the solution with nitrogen).

[0180] With the stirrer running (200-300 rpm), 181.41 g of sodium disulfite are loaded into the reactor and stirred for at least 10 minutes until completely dissolved. Then 9.07 kg (in terms of the main substance) of sodium chondroitin sulfate are loaded into the reactor in portions and stirred for at least 60 minutes until completely dissolved.

[0181] Next, 45.35 g of methyl parahydroxybenzoate are loaded into the reactor, stirred for at least 20 minutes, and a sample is taken. The pH of the resulting solution is measured, if necessary, its value is brought to 6.8 with 1 M sodium hydroxide solution, the solution is stirred for at least 10 minutes, then 1763.32 mg of iron gluconate dihydrate (in terms of containing 14 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance is manufactured by Pfizer Inc., Germany) are added while stirring, then the solution is brought to the calculated volume (20 l) with water for injection and stirred for at least 15 minutes.

[0182] After analysis and adjustment (if necessary), the solution is subjected to sterilizing filtration and poured into 1 ml ampoules. Example 5. Preparation of tablets

[0183] Option 1: Tablet containing chondroitin sulfate and glucosamine hydrochloride.

[0184] The composition in the form of a tablet can be manufactured as follows: 48.96 kg of sodium chondroitin sulfate, 48.96 kg of glucosamine hydrochloride, 2.67 g of iron sulfate (in terms of containing 20 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The substance manufacturer is Dr. Paul Lomani GmbH, Germany) are mixed in a drum mixer. The resulting mixture is molded and pressed, then dried to the required residual moisture and calibrated. Then it is enclosed in a hard shell with the following composition: hydroxypropyl methylcellulose - 116.52 g, titanium dioxide - 26.44 g, triacetin - 23.50 g, calcium sulfate - 763.06 g, microcrystalline cellulose - 615.91 g, croscarmellose - 266.34 g, stearic acid - 233.05 g, magnesium stearate - 33.29 g.

[0185] Option 2: A tablet containing chondroitin sulfate.

[0186] The composition in the form of a tablet can be manufactured as follows: weighed sodium chondroitin sulfate - 64.67 kg, iron sulfate - 4.76 g (in terms of containing 27 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lomani GmbH Germany), calcium stearate - 1.29 kg; kollidon - 3.10 kg; povidone-KZ0 - 2.51 kg, microcrystalline cellulose - 25.47 kg; magnesium hydrogen carbonate pentahydrate - 2.95 kg are mixed in a drum mixer. The resulting mixture is molded and pressed, then dried to the required residual moisture content and calibrated.

[0187] Option 3: Tablet containing chondroitin sulfate and glucosamine hydrochloride.

[0188] The composition in the form of a film-coated tablet can be manufactured as follows: 48.49 kg of sodium chondroitin sulfate, 48.49 kg of glucosamine hydrochloride, 4.62 g of iron sulfate (in terms of containing 35 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lomani GmbH, Germany), 1116 g of methylsulfonyl, 775.83 g of cellulose, 465.50 g of calcium hydrogen phosphate dihydrate, 279.30 g of stearic acid, 193.96 g of sodium croscarmellose, 38.79 g of magnesium stearate, 15.52 g of colloidal silicon dioxide are mixed. The resulting mixture is molded and pressed, then dried to the required residual moisture content and calibrated. Then it is enclosed in a shell, which may have the following composition: hypromellose 1.84 g, polydextrose - 31.03 g, titanium dioxide 150 mg, talc - 30 mg, maltodextrin - 20 mg, triglycerides 2.33 g, E110 - 3.88 g.

[0189] Example 6. Preparation of capsules

[0190] Option 1: Capsules containing 160 mg sodium chondroitin sulfate per capsule.

[0191] The composition can be prepared in the following way: 7.11 g of iron fumarate (in terms of containing 25 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Teva Pharmaceutical Industries Ltd., Israel) are mixed with 4.3 g of lactose, 569.77 g of polyvinylpyrrolidone and 244.19 g of sodium croscarmellose,

[0192] Grind in a ball mill. Add 15 liters of distilled water to the resulting mixture, stir the mass and add 697.67 g of sodium dodecyl sulfate. Stir the mass until it is homogeneous. Then granulate and dry at 36-40 °C, grind and sift through a 0.5 µm sieve. Mix the granulate with 93.02 kg of sodium chondroitin sulfate and 1.16 kg of magnesium stearate.

[0193] Option 2: Capsules containing 200 mg sodium chondroitin sulfate per capsule.

[0194] The composition can be prepared as follows: 8.52 g of iron fumarate (in terms of containing 30 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The manufacturer of the substance is Teva Pharmaceutical Industries Ltd., Israel) are mixed with 4.64 g of lactose, 696.7 g of polyvinylpyrrolidone and 278.68 g of sodium croscarmellose. Grind in a ball mill. 18-20 l of distilled water are added to the resulting mixture, the mass is stirred and 557.36 g of sodium dodecyl sulfate are added. The mass is stirred until homogeneous kkoonnns ... The granulate is mixed with 92.89 kg of sodium chondroitin sulfate and 928.94 g of magnesium stearate.

[0195] Option 3: Capsules containing 180 mg sodium chondroitin sulfate per capsule.

[0196] The composition can be manufactured as follows: 10.43 g of ferrous fumarate (in terms of containing 37 mg of elemental iron per 1 kg of sodium chondroitin sulfate. The manufacturer of the substance is Dr. Reddy's Ltd., India) are mixed with 4.15 kg of lactose, 1.08 kg of polyvinylpyrrolidone and 215.03 g of sodium croscarmellose. Grind in a ball mill. 18-20 l of distilled water are added to the resulting mixture, the mass is stirred and 614.38 g of sodium dodecyl sulfate are added. The mass is stirred until a homogeneous consistency is obtained. Then the mixture is granulated and dried at 36-40 °C, crushed and sifted through a 0.7 μm sieve. The granulate is mixed with 92.15 kg of sodium chondroitin sulfate and 1.79 kg of magnesium stearate.

[0197] The final quality control of the preparations in all the described forms of release was carried out using the methods described in the State Pharmacopoeias, normative and information-methodical ddookkuummeennttaahh. There are several methods (titrimetric, colorimetric, spectrometric) for quantitative determination of the content of elemental iron. The most sensitive (accurate) methods are spectrometric. Within the framework of this invention, atomic absorption spectrometry (OFS 1.2.11.0005.18 SP RF) and atomic emission spectrometry with inductively coupled plasma (OFS.1.2.1.1.0004.15 SP RF) were used.

[0198] The examples presented above show that the preparation of drugs can be implemented in different dosage forms using various methods and auxiliary substances, which do not influence the final result, since the functional role of the agent for the treatment of arthrological diseases and the achievement of the declared technical result is determined by the active substance based on sodium chondroitin sulfate with the addition of iron from 1 mg to 40 mg per 1 kg of sodium chondroitin sulfate.

[0199] Research

[0200] Animal studies were conducted to evaluate the therapeutic efficacy of the inventive agents. The study was conducted by comparing 6 preparations of different release forms. For each release form, preparations were manufactured that corresponded to one of the manufacturing options. Preparations of similar release forms, differing in composition by the absence of iron, were used as comparison preparations.

[0201] Drugs involved in the study

[0202] The list of drugs studied is given in Table 1. Table 1

[0203] Doses, duration of course, method of administration

[0204] In accordance with the guidelines for studying the overall effectiveness of pharmacological agents, the minimum dose when studying side effects should be close to the therapeutic dose.

[0205] Based on data on therapeutic doses and metabolic coefficients for each study drug and comparison drugs, the following course of administration and daily doses (mg / kg) were established:

[0206] Table 2

[0207] Experimental groups

[0208] To conduct the studies, the drugs and animals were divided into 6 groups depending on the form of release, which in turn were divided into two groups (the drug under study and the comparison drug):

[0209] Table 3 Animals for research

[0210] The determination of the indicators was carried out on rabbits.

[0211] The experiments were performed on Chinchilla rabbits aged 12-14 months, weighing 2.7 ± 0.5 kg.

[0212] The randomization method was used to distribute animals into groups. The absence of external signs of disease and homogeneity of groups by body weight (±10%) were considered as criteria for acceptability of randomization.

[0213] Quarantine

[0214] The quarantine period for all animals was 14 days. During the quarantine, each animal was examined daily (behavior and general condition), and animals were observed in cages twice a day (morbidity and mortality).

[0215] Before the study, animals that met the inclusion criteria were randomly assigned to groups. Animals that did not meet the criteria were excluded from the study during quarantine.

[0216] Animal care

[0217] The animals were kept in accordance with the requirements of GOST R from 02.12.2009 53434-2009 "Principles of Good Laboratory Practice (GLP)". The animals were kept in ventilated cages "Rair Iso System", in groups of 5 animals. Sterile wood sawdust from non-coniferous trees was used as bedding. The feed was standard granulated complete feed for laboratory animals (extruded) PK-120 GOST R 51849-2001 R.5. The animals were fed according to the standards in the SSOOOOOOOVETTSSTVIIIIII with the animal species. Purified tap water was given to all animals ad libitum in standard drinkers. The animals were kept in controlled environmental conditions: air temperature 22-24 °C and relative humidity 60-70%. The lighting in the rooms was natural and artificial. A 12-hour lighting cycle was maintained in the animal holding rooms.

[0218] Observation period and recorded indicators

[0219] The observation period was 52 days.

[0220] Animals from groups A1, B1, B1, G1, D1, E1 underwent destruction 30 days before the start of the study by 6-fold injections of papain with an interval of 5 days into the cavity of the right knee joint at a dose of 50 mg per injection (1 ml of 5% solution). Upon completion of the course of administration, animals of all groups were euthanized by an overdose of ether and sent for autopsy.

[0221] The general condition of the animals was assessed by daily inspection. Weighing, rectal temperature measurement, water and food consumption were performed once every two weeks and after the end of the experiment.

[0222] Every 3 days, an ultrasound examination of the thickness of the articular cartilage of the knee joint and an assessment of the pain in the knee joint were performed.

[0223] Every 5 days, the diameter of the destroyed joint was measured to assess swelling.

[0224] Methods of performance evaluation

[0225] Articular cartilage thickness test

[0226] The thickness of the articular cartilage of the rabbit knee joint was measured using ultrasound. Measurements were taken 31 days before the start of the study and destruction of the knee joint with papain, on the first day of using the means according to the invention, then every 3 days during the course of treatment and at the end of the study on the 52nd day.

[0227] Data processing

[0228] After the study, all results were entered into a table for each indicator and subgroup. The time, degree and dynamics of complete and partial regeneration of articular cartilage were assessed.

[0229] Results of the study of articular cartilage thickness

[0230] Gel dosage form

[0231] The studies were conducted on animals of Group No. 1 (G1). The results of the study are shown in Table 4. Table 4.

[0232] The dynamics of changes in the thickness of articular cartilage is shown in the graph (Fig. 1).

[0233] Ointment dosage form

[0234] The studies were conducted on animals of Group No. 2 (G2). The results of the study are shown in Table 5.

[0235] Table 5.

[0236] The dynamics of changes in the thickness of articular cartilage is shown in the Graph (Fig. 2). Lyophilisate for intramuscular administration.

[0237] The studies were conducted on animals of Group No. 3 (GZ). The results of the study are shown in Table 6.

[0238] Table 6.

[0239] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 3).

[0240] Solution for intramuscular administration.

[0241] The studies were conducted on animals of Group No. 4 (G4). The results of the study are shown in Table 7.

[0242] Table 7.

[0243] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 4). Tablet dosage form

[0244] The studies were conducted on animals of Group No. 5 (G5). The results of the study are shown in Table No. 8.

[0245] Table 8.

[0246] The dynamics of changes in the thickness of articular cartilage is shown in the graph (Fig. 5).

[0247] Capsulated dosage form

[0248] The studies were conducted on animals of Group No. 6 (Gb). The results of the study are shown in Table 9.

[0249] Table 9.

[0250] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 6). Conclusion

[0251] The results of all studies are presented in Table 9.

[0252] Table 9.

[0253] The results of studies on all dosage forms lead to an unambiguous conclusion about significant advantages of the means according to the invention compared to the comparison drugs. The use of the claimed compositions leads to a reduction in the duration of therapy and more complete regeneration of cartilage tissue. In the case of using the means according to the invention, the courses of treatment can be significantly shortened.

[0254] Also, the preparations according to the invention showed a greater dynamics of increasing the thickness of the cartilage. This conclusion is confirmed by the graphs of the dynamics of the growth of the thickness of the cartilage. Almost all the graphs show that the means according to the invention begin to act from the very beginning of the course of treatment. This effect is especially noticeable in the graphs reflecting the dynamics of cartilage growth for the solution and lyophilisate (Fig. 3 and Fig. 4).

Claims

CLAUSE OF INVENTION 1. An agent for the treatment of arthrological diseases, comprising an effective amount of sodium chondroitin sulfate and at least one auxiliary substance or carrier, characterized in that it additionally contains iron in a relative amount of 1 mg / kg to 40 mg / kg, based on the weight of sodium chondroitin sulfate.

2. The agent according to item 1, in which the amount of sodium chondroitin sulfate is from 50 mg to 2500 mg.

3. The agent according to claim 1, wherein the amount of sodium chondroitin sulfate is from 100 mg to 2000 mg.

4. The agent according to claim 1, wherein the amount of sodium chondroitin sulfate is from 300 mg to 1500 mg.

5. The agent according to claim 1, wherein the amount of sodium chondroitin sulfate is from 500 mg to 1200 mg.

6. The agent according to claim 1, wherein the amount of sodium chondroitin sulfate is from 50 mg to 250 mg.

7. The agent according to claim 1, wherein the amount of sodium chondroitin sulfate is from 250 mg to 1000 mg.

8. The agent according to I.1, which contains iron in a relative amount from 2 mg / kg to 20 mg / kg based on the weight of sodium chondroitin sulfate.

9. The agent according to I.1, which contains iron in a relative amount from 1 mg / kg to 18 mg / kg, calculated on the weight of sodium chondroitin sulfate.

10. The agent according to I.1, which contains iron in a relative amount from 1 mg / kg to 16 mg / kg, calculated on the weight of sodium chondroitin sulfate.

11. The agent according to I.1, which contains iron in a relative amount from 3 mg / kg to 30 mg / kg based on the mass of sodium chondroitin sulfate.

12. The agent according to item 1, which contains iron in a relative amount of 10 mg / kg to 32 mg / kg based on the weight of sodium chondroitin sulfate.

13. The agent according to item 1, which contains iron in a relative amount of 10 mg / kg to 35 mg / kg based on the weight of sodium chondroitin sulfate.

14. The agent according to item 1, which contains iron in a relative amount of 17 mg / kg to 37 mg / kg based on the weight of sodium chondroitin sulfate.

15. The agent according to item 1, which contains iron in a relative amount of 4 mg / kg to 28 mg / kg based on the weight of sodium chondroitin sulfate.

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