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] A PHARMACEUTICAL PRODUCT FOR THE TREATMENT OF ARTHROLOGICAL DISEASES

[0002] FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

[0003] The invention relates to the field of medicine, in particular to medicinal products for the treatment of arthrological diseases.

[0004] LEVEL OF TECHNOLOGY

[0005] According to the World Health Organization, musculoskeletal disorders are the leading cause of disability worldwide. These conditions limit mobility and motor skills, leading to premature retirement from work and reduced ability to perform social functions.

[0006] Degenerative joint disease, or osteoarthritis (OA), is the most common form of joint disease, with the knee joint most frequently affected. Each year, more than four million new patients seek medical attention due to knee pain. An estimated 10% of the population over 55 years of age exhibit signs of knee deterioration, with approximately 25% of these patients experiencing significant problems that impact their quality of life. According to the WHO Global Burden of Disease report, knee OA is a leading cause of disability: the fourth leading cause among women and the eighth leading cause among men. Osteoarthritis can affect anyone, regardless of gender, age, race, or skin color. The primary manifestations of OA include disruption of articular cartilage structure, subchondral bone remodeling, and osteophyte formation (joint ossification).The disease has a chronic, progressive course, with exacerbations most often occurring under the influence of mechanical factors, and destructive changes progressively increasing. OA occurs not only in the elderly but also in the working-age population, often leading to decreased mobility and even disability, the socioeconomic cost of which is very high. The onset of OA is closely linked to age: before age 50, the disease is more common in men, and after age 50, in women, resulting from estrogen deficiency during menopause. The incidence of the disease in women and men becomes equal around age 80.

[0007] Supporting joint function is based on chondromodulatory therapy, which currently widely uses medications based on sodium chondroitin sulfate, a mucopolysaccharide derived from animal tissue. This medication effectively influences metabolic processes in the patient's connective tissue, including cartilage, stimulating and normalizing the biosynthesis of glycosaminoglycans.

[0008] Chondroitin sulfate (CS) is a high-molecular heteropolysaccharide that belongs to the group of glycosaminoglycans, linear unbranched polymers.

[0009] The structure of the cholesterol molecule determines its polyanionic properties and its role in transporting water, amino acids, and lipids in avascular areas of cartilage. Long chains of cholesterol, which are part of the extracellular matrix, determine the most important biomechanical properties of cartilage tissue. Chlorhexidine is a structural modulator that is not only synthesized by the body but also, after administration, integrates into cartilage structures, stimulating synthesis and inhibiting destruction. Its timely administration and regular use ensure the inhibition, stabilization, and prevention of destructive processes in the joint. The main function of cholesterol in the body is to retain water and nutrients in cartilage and facilitate the movement of molecules through it. This is a crucial property, as cartilage lacks blood to support metabolism. Chlorhexidine also acts as a chondroprotector.The water it retains within the cartilage provides good cushioning and absorbs shock, which ultimately increases the strength of the connective tissue.

[0010] HS is a natural component of articular cartilage that plays a vital role in maintaining the necessary osmotic pressure, allowing the matrix and collagen fibers to stretch. This substance has anti-inflammatory activity, primarily affecting the cellular component of inflammation, stimulating the synthesis of hyaluronic acid and proteoglycans, and inhibiting the action of proteolytic enzymes.

[0011] Chondroitin sulfate preparations

[0012] There are currently a significant number of cholesterol-containing drugs on the market. They are divided into three main groups:

[0013] 1. Topical agents. 2. Oral agents.

[0014] 3. Parenteral agents.

[0015] The 1st group includes:

[0016] Chondroitin ACOS ointment is for external use. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. Repeat if necessary.

[0017] Chondroitin Ointment is a topical medication. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. Repeat if necessary.

[0018] Osteoregin ointment is for external use. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The treatment course is 2-3 weeks. Repeat if necessary.

[0019] Ambene Chondro Gel is a topical medication. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The course of treatment lasts from 2-3 weeks to 2-3 months. Repeat if necessary.

[0020] Sustamhondro ointment is used topically. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The course of treatment lasts from 2-3 weeks to 2-3 months. Repeat if necessary.

[0021] Artravir Trivium ointment is for topical use. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, repeat the course after consulting a doctor.

[0022] Artrafik ointment is for external use. Apply 2-3 times daily to the skin over the affected area and rub in for 2-3 minutes until completely absorbed. The course of treatment is 2-3 weeks. If necessary, repeat the course after consulting a doctor.

[0023] Chondroglucide gel is a topical medication. Apply a thin 4 cm (2 g) layer of the gel to intact skin over the affected area 2-3 times daily, then rub in for 2-3 minutes until absorbed. Treatment duration is 1 month. A repeat course may be recommended by a physician. The main problem with topical agents is their low bioavailability and short duration of action. Therefore, topical agents are often used in conjunction with parenteral medications. When used alone, patients are forced to frequently repeat courses, which have low therapeutic efficacy.

[0024] The 2nd group includes:

[0025] The medication "Structum" is for oral administration. Take 1 capsule (500 mg) twice daily. The recommended course of treatment is 6 months.

[0026] Ambene Chondro is an oral medication. The recommended dose is 2 capsules (250 mg) twice daily or 1 capsule (500 mg) twice daily. The recommended course of treatment is 6 months.

[0027] Chondroitin Velpharm is an oral medication. Prescribed at a dose of 1 g (2 capsules of 250 mg or 1 capsule of 500 mg) twice daily. The recommended course of treatment is 6 months.

[0028] Artrafik is an oral medication. The prescribed dose is 1 g / day, 500 mg twice daily, or 2 capsules of 250 mg twice daily. The recommended course of treatment is 6 months.

[0029] The medicinal product "ARTRAVIR®-TRIVIUM®" is for oral administration. The prescribed dose is 1 g per day – 2 capsules of 250 mg or 1 capsule of 500 mg twice daily. The recommended initial treatment duration is 6 months.

[0030] Chondroitin-AKOS capsules. For oral administration. Prescribed at 1 g per day – 2 capsules twice daily. The recommended initial treatment duration is 6 months.

[0031] Chondroitin-VERTEX capsules. Prescribed at 1 g per day – 2 capsules twice daily. The recommended initial course of treatment is 6 months.

[0032] Chondroxide tablets. Taken orally, 0.5 g (2 tablets) twice daily. The recommended initial course of treatment is 6 months.

[0033] Combination medications containing chondroitin sulfate and glucosamine are also available in tablet and capsule form. These medications include Artra (tablets), Artravir - Trivium Complex (capsules), Artrafik Pro (capsules), and Tazan (tablets). These medications offer a combined effect due to the presence of two active ingredients. However, the course of treatment is similar to that of medications with a single active ingredient and should last at least 6 months. Repeated courses are also necessary.

[0034] Thus, oral medications, like ointments and gels, have low bioavailability. According to various literature sources, it ranges from 8 to 13%. They also often contain low-quality ingredients. These medications are recommended for prophylactic use. Treatment with these medications is long (at least 6 months), expensive, and short-lived. Repeat courses are necessary, as the medication's effect lasts no more than 3 months after completing the full course.

[0035] The 3rd group includes:

[0036] Mucosat solution for intramuscular and intra-articular injection. 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. A course of treatment consists of 25-30 injections. If necessary, repeat courses can be administered after 6 months. For callus formation, a course of treatment is 3-4 weeks (10-14 injections every other day).

[0037] Artogystan solution for intramuscular injection. Administered intramuscularly, 100 mg every other day. If well tolerated, the dose is increased to 200 mg, starting with the fourth injection. A course of treatment consists of 25-35 injections. If necessary, a repeat course of treatment can be administered after 6 months.

[0038] Chondrogard solution for intramuscular and intra-articular administration. Administer 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 consists of 25-30 injections. If necessary, a repeat course of treatment can be administered after 6 months. For osteoarthritis of large joints, a combination of intra-articular and intramuscular administration 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 are administered with a 1-day interval between injections (every other day). Depending on the joint size, up to 2 ml of Chondrogard can be injected into the joint cavity.

[0039] Injectran solution for intramuscular and intra-articular administration. Administer 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 consists of 25-30 injections. If necessary, a repeat course of treatment can be administered after 6 months. For osteoarthritis of large joints, a combination of intra-articular and intramuscular administration is possible. Up to 5 intra-articular injections of 2 ml are administered with a 3-day interval between injections, and 16 intramuscular injections of 2 mg are administered with a 1-day interval between injections (every other day). Depending on the joint size, up to 2 ml of Injectran can be injected into the joint cavity.

[0040] Mucosat solution for intramuscular and intra-articular administration. The drug is administered intramuscularly at a dose of 100 mg (1 ml) every other day. If well-tolerated, the dose is increased to 200 mg (2 ml), beginning with the fourth injection. A course of treatment consists of 25-30 injections. If necessary, repeat courses can be administered after 6 months.

[0041] To form bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0042] For osteoarthritis of large joints, a combination of intra-articular and intramuscular administration 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 are administered with a 1-day interval between injections (every other day).

[0043] Intra-articular administration is performed under aseptic conditions by a specialist trained in intra-articular injection technique. Depending on the joint size, up to 2 ml of Mucosat can be injected into the joint cavity.

[0044] After intra-articular injection of the drug, the puncture site is lubricated with an alcohol wipe and a bactericidal plaster is applied.

[0045] Chondroitin-Apex solution for intramuscular injection. Administer 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 repeat course of treatment can be administered after 6 months. The duration of repeat courses is determined by the physician. For callus formation, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0046] Chondroitin-B 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), beginning with the fourth injection. A course of treatment consists of 25-35 injections. If necessary, a repeat course of treatment can be administered after 6 months. The duration of repeat courses is determined by the physician. For callus formation, a course of treatment is 3-4 weeks (10-14 injections every other day).

[0047] Chondroitin-Binergia solution for intramuscular and intra-articular administration. The drug is administered intramuscularly at a dose of 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), beginning with the fourth injection. A course of treatment consists of 25-35 injections. If necessary, a repeat course of treatment can be administered after 6 months.

[0048] For osteoarthritis of large joints, a combination of intra-articular and intramuscular administration is possible. Up to 5 joint injections of 2 ml each are administered with a 3-day interval between injections, and 16 intramuscular injections of 2 ml each are administered with a 1-day interval between injections (every other day).

[0049] Intra-articular injection of the drug is performed under aseptic conditions by a specialist trained in intra-articular injection technique. Depending on the joint size, up to 2 ml of the drug can be injected into the joint cavity.

[0050] After intra-articular injection of the drug, the puncture site is lubricated with an alcohol wipe and a bactericidal plaster is applied.

[0051] To form bone callus, the course of treatment is 3-4 weeks (10-14 intramuscular injections every other day).

[0052] Chondroitin sulfate solution for intramuscular injection. The drug is administered intramuscularly at a dose of 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), beginning with the fourth injection. A course of treatment consists of 25-30 injections. If necessary, repeat courses can be administered after 6 months.

[0053] To form bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0054] Chondrofast solution for intramuscular injection. The drug is administered intramuscularly at a dose of 100 mg (1 ml) every other day. If well tolerated, the dose is increased to 200 mg (2 ml), beginning with the fourth injection. A course of treatment consists of 25-30 injections. If necessary, repeat courses can be administered after 6 months.

[0055] To accelerate the formation of bone callus, the course of treatment is 3-4 weeks (10-14 injections every other day).

[0056] The medicinal product "Khonsat solution for intramuscular injection".

[0057] The drug is administered intramuscularly at a dose of 1 ml (100 mg) every other day. If well tolerated, the dose is increased to 2 ml (200 mg), beginning with the fourth injection. A course of treatment consists of 25-30 injections. If necessary, repeat courses can be administered after 6 months.

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

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

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

[0061] Parenteral chondroitin sodium sulfate preparations are most effective. This is due to its high bioavailability. After an intramuscular injection, sodium chondroitin sulfate is detectable in the synovial fluid within 15 minutes. It then enters the joint, where it reaches its peak concentration within 48 hours.

[0062] The disadvantages of these medications include similar side effects, such as allergic reactions (itching, erythema, urticaria, dermatitis, swelling) and hemorrhages at the injection site. Since the above-mentioned medications require a long treatment course (at least 25 injections), this inevitably leads to an increased incidence of these side effects. Furthermore, long courses are inconvenient for patients, as they require at least 25 days of treatment in the treatment room, and not all medical professionals are trained in administering these injections, especially intra-articular ones. This leads to patients not completing full courses of treatment, significantly reducing the effectiveness of the treatment. Furthermore, all of these medications require repeat courses at least six times a year, which further complicates treatment for patients and can lead to reluctance to continue treatment.

[0063] Use of iron

[0064] The role of iron in metabolism

[0065] Iron helps support many vital bodily functions, affecting energy levels, concentration, gastrointestinal function, the immune system, and body temperature regulation. Its deficiency or excess immediately impacts well-being. Iron is an essential component of hemoglobin, the constituent of red blood cells. Hemoglobin contains approximately two-thirds of the body's iron. It combines with oxygen, and red blood cells carry it from the lungs throughout the body. This mineral is also a component of many elements responsible for cholesterol metabolism, the conversion of calories into energy, the fight against toxins, and is involved in stopping inflammation. Iron enhances the immune system's function, and red blood cells use it to transport carbon dioxide to the lungs for recycling. It is also essential for maintaining healthy cells, skin, hair, and nails.Iron metabolism disorders can have a variety of clinical manifestations, including anemia (a decrease in hemoglobin concentration and / or red blood cell count) and hemochromatosis (a hereditary disorder that causes iron accumulation in tissues). Iron in the human body is a component of many enzymes and proteins essential for metabolic processes, including the breakdown and utilization of toxins, cholesterol metabolism, and the conversion of calories into energy. It also helps the body's immune system fight off invaders. A dose of elemental iron no more than 20 mg / kg body weight is nontoxic, 20 to 60 mg / kg body weight is slightly and moderately toxic, and >60 mg / kg body weight can cause symptoms of severe poisoning. Various iron compounds are used in medicine, including ferrous sulfate, ferrous fumarate, iron 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. A vitamin and mineral complex. Contains iron in the form of ferrous sulfate, folic acid, and vitamin B12. Used as a preventative measure for conditions associated with increased vitamin and iron requirements.

[0069] Ferroplex tablets. Contain iron as ferrous sulfate, vitamins B12, 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 B12. Prescribed for: iron-, folate-, and B12-deficiency anemia caused by prolonged bleeding (including blood loss due to surgery); diets and impaired iron absorption from the gastrointestinal tract; to improve physical development;

[0071] Maltofer tablets. Contain iron hydroxide. Used to treat anemia caused by iron deficiency and to prevent iron deficiency.

[0072] Totema is an oral solution. Contains iron gluconate dihydrate, manganese, and copper. It is used to prevent and treat iron deficiency anemia.

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

[0074] Ferrum Lek is a solution for intramuscular injection. Contains iron hydroxide. It is used to treat anemia.

[0075] Sorbifer Durules tablets contain ferrous sulfate and ascorbic acid. They are 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, additionally containing iron and having high efficiency, which includes the active substance - sodium chondroitin sulfate.

[0080] The stated objectives are achieved by creating a means for the treatment of 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 of high efficacy, enhanced regeneration and accelerated growth of cartilage tissue, and increased cartilage thickness. It has been found that the introduction of a certain amount of iron into compositions containing sodium chondroitin sulfate leads to a shorter treatment course, increased rate of cartilage regeneration, and reduced side effects.

[0082] The use of the agent according to the invention leads to the normalization of metabolic processes, acceleration of the removal of swelling 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 supplements.

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

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

[0086] The amount of iron compound used in 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 appropriate for the intended purposes. The claimed product contains an effective amount of sodium chondroitin sulfate. An effective amount is defined as the amount that produces 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 specific case, the amount of sodium chondroitin sulfate in the product may range from 250 mg to 1000 mg. In a specific case, the amount of sodium chondroitin sulfate in the product may range 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 manufacturing form 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 auxiliary substances selected from the group: dimethyl sulfoxide, propylene glycol, carbomer, trolamine, macrogol, edetate, neroli and lavender oils, lanolin, petrolatum.

[0115] The tablet formulation may additionally contain glucosamine hydrochloride. The glucosamine hydrochloride to sodium chondroitin sulfate weight ratio may range from 0.5 to 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 stated medication is intended for the treatment of arthrological diseases. The dosage and daily dose of sodium chondroitin sulfate depend on the form of the medication.

[0126] For injectable and lyophilized products, the dosage is 100 mg / ml of sodium chondroitin sulfate, with a daily dose of 200 mg. It is administered intramuscularly every other day.

[0127] For tablets and capsules, the dosage of sodium chondroitin sulfate is 500 mg. The daily dose is 1000 mg. Take 2-3 capsules / tablets orally per day.

[0128] For ointments and gels, the dosage of sodium chondroitin sulfate is 5.0 g per 100 g. It is applied externally to the affected joints 2-3 times a day.

[0129] These conditions 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 associated with systemic lupus erythematosus, dermatomyositis and other systemic diseases, psoriatic arthritis, post-traumatic injuries to articular cartilage, ligaments, and menisci. BRIEF DESCRIPTION OF DRAWINGS

[0130] Fig. 1 - Graph of changes in articular cartilage thickness in animals of Group No. 1 (G1). Fig. 2 - Graph of changes in articular cartilage thickness in animals of Group No. 2 (G2). Fig. 3 - Graph of changes in articular cartilage thickness in animals of Group No. 3 (G3). Fig. 4 - Graph of changes in articular cartilage thickness in animals of Group No. 4 (G4). Fig. 5 - Graph of changes in articular cartilage thickness in animals of Group No. 5 (G5). Fig. 6 - Graph of changes in articular cartilage thickness in animals of Group No. 6 (Gb).

[0131] IMPLEMENTATION OF THE INVENTION

[0132] Examples of the preparation of various formulations with sodium chondroitin sulfate and iron, which are not exhaustive.

[0133] Example 1. Preparation of gel

[0134] A preparation in the form of a gel, including sodium chondroitin sulfate, purified water, and which additionally contains iron in a relative quantity of 1 mg / kg to 40 mg / kg based on the weight of sodium chondroitin sulfate, can be obtained using various excipients.

[0135] Option 1:

[0136] 100 kg of the drug 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 liters of purified water. Then solution No. 2 is prepared: dissolving 39.98 g of methyl parahydroxybenzoate in 8 liters of ethanol. To obtain solution No. 3, mix in 72.51 liters 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 (based on 2 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: Dr. Paul Lohmani GmbH, Germany). The solutions are then mixed until a gel mass is formed. Flavorings are added (wt / vol%): lavender oil - 39.98 g; orange flower oil (neroli oil) - 19.99 g.

[0137] Option 2:

[0138] 100 kg of the drug 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: dissolving 41.08 g of nipagin in 6.16 l of ethanol. To obtain solution No. 3, mix 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 (equivalent to 8 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: Dr. Paul Lohmann GmbH, Germany). Solutions 1, 2, and 3 are then mixed until a gel forms. Flavorings are added: lavender oil – 41.08 g; orange blossom oil (neroli oil) – 20.54 g.

[0139] Option 3:

[0140] To prepare 100 kg of the product, prepare solution #1 by adding 749.58 g of carbomer to 35.98 liters of purified water and stirring. Then prepare solution #2 by dissolving 29.98 g of methyl parahydroxybenzoate in 4497.48 ml of ethanol. Solution No. 3 is obtained by stirring 54.52 l of purified water, 1,500 g of sodium chondroitin sulfate, 149.92 g of glucosamine hydrochloride, 299.83 g of methylsulfonylmethane, 3 g of sodium metabisulfite, 1,500 g of propylene glycol, 749.58 g of carbomer, 1% iron gluconate solution - 12.10 ml (based on containing 10 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer of the substance Dr. Paul Lohmann GmbH, Germany) while heating to a temperature of 70 °C. The solutions are then stirred for several hours until a gel mass is formed. If necessary, add fragrance in the amount of 14.99 g.

[0141] Example 2. Preparation of ointment

[0142] 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.

[0143] Option 1:

[0144] 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 stir, then cool 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) is 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.

[0145] Option 2:

[0146] Vaseline (35.71 kg), anhydrous lanolin (15.31 kg), stearic acid (3.06 kg), and pentol (5.10 kg) are melted at 70±2°C, stirred, and then cooled to 55±2°C (ointment base). Sodium chondroitin sulfate (5.10 kg) is dissolved in 20.35 l of distilled water. Sodium diclofenac (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 Dr. Paul Lohmani 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.

[0147] Option 3:

[0148] To produce 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 a mixer. Heat the mixture to 60-65 °C and stir until smooth. During mixing, add 15.03 g of dimethyl sulfoxide in small portions. Dissolve 1.51 kg of sodium chondroitin sulfate in 20.1 L of purified water. Add 48.63 ml of 1% ferrous gluconate solution (containing 40 mg of elemental iron per 1 kg of sodium chondroitin sulfate; manufacturer: Dr. Paul Lohmani GmbH, Germany) to the solution while stirring. The resulting solution is added to the ointment base, brought to 100 kg with purified water, and stirred until completely homogenized.

[0149] Example 3. Preparation of lyophilisate

[0150] The drug 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.

[0151] The injection solution prepared from the said lyophilisate using apyrogenic water contains Na-salt of chondroitin sulfate in a therapeutic dosage of 9.0-11.5 wt%.

[0152] The drug can be obtained, for example, in the following way:

[0153] Option 1:

[0154] Dissolve 10.2 kg of a substance containing 90-115% sodium chondroitin sulfate in 89.77 L of pyrogen-free water for injection. Add 30 g of sodium disulfite with stirring. Adjust the pH to 6.0 to 7.5 with sodium hydroxide solution, then add 141.67 mg of ferrous gluconate dihydrate (containing 1 mg of elemental iron per 1 kg of sodium chondroitin sulfate; manufacturer: Pfizer Inc., Germany). Perform sterilizing filtration, dispense into 1 ml ampoules, and sublimate using a known method. The ampoules containing the lyophilized drug are sealed.

[0155] Option 2:

[0156] Dissolve 10.4 kg of a substance containing 90-115% sodium chondroitin sulfate in 89.57 L of pyrogen-free water for injection, and add 30 g of sodium disulfite with stirring. Adjust the pH to 6.0 to 7.5 with sodium hydroxide solution, then add 722.19 mg of ferrous gluconate dihydrate (containing 5 mg of elemental iron per 1 kg of sodium chondroitin sulfate; manufacturer: Novartis AG, Switzerland). Perform sterilizing filtration, dispense into 1 ml ampoules, and sublimate using a known method. The ampoules containing the lyophilized drug are sealed.

[0157] Option 3:

[0158] Dissolve 10.3 kg of a substance containing 90-115% sodium chondroitin sulfate in 89.67 L of pyrogen-free water for injection. Add 30 g of sodium disulfite with stirring. Adjust the pH to 6.0 to 7.5 with sodium hydroxide solution, then add 1144.37 mg of ferrous gluconate dihydrate (containing 8 mg of elemental iron per 1 kg of sodium chondroitin sulfate; manufacturer: Novartis AG, Switzerland). Perform sterilizing filtration, dispense into 1 ml ampoules, and sublimate using a known method. The ampoules containing the lyophilized drug are sealed.

[0159] Example 4. Preparation of solution

[0160] 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.

[0161] Option 1:

[0162] Preparation of solution "A": Dissolve 10.42 kg of sodium chondroitin sulfate (based on the active ingredient content) in 52.08 L of water for injection, heated to 50°C. After the chondroitin sulfate is completely dissolved, cool the solution to a temperature no higher than 35°C.

[0163] Preparation of solution "B": Add 36.46 liters of water for injection 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 ferrous gluconate dihydrate (containing 4 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: Novartis AG, Switzerland).

[0164] Preparation of solution "G". Add 35 liters of solution "B" to solution "A" with constant stirring, along with 0.1 M NaOH to a pH of 6-6.5 and water for injection to bring the volume to 100 liters. The solution is analyzed for the content of the essential substances and its pH, and adjusted if necessary. Solution "G" is sterilized and filtered into a sterile container. The solution is dispensed into 1.0 ml ampoules and sealed.

[0165] Option 2:

[0166] Preparation of solution "A": Dissolve 10 kg of sodium chondroitin sulfate (calculated as absolutely dry substance) in 40 liters of injection water heated to 50°C. After the sodium chondroitin sulfate is completely dissolved, cool the solution to room temperature, bring the volume to 40 liters with injection water, and sterilize-filter.

[0167] Preparation of solution "B": Add 25 liters of water for injection 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. Manufacturer: Pfizer Inc., Germany).

[0168] Preparation of solution "B". Dissolve 0.05 g of sodium hydroxide in 24 l of water for injection.

[0169] Preparation of solution "G." Sterilely filter 50 L of solution "B" into sterile solution "A" while constantly stirring. Then, 15-20 minutes after adding solution "B," while continuing to stir, sterilely filter 25 L of solution "B." Stirring is continued for 15-20 minutes after adding solution "B."

[0170] Preparation of the drug. The required amount (up to 100 liters) of water for injection is added to the sterile container containing solution "G" through a sterilizing filter.

[0171] Filling the solution. The solution is poured into 1 ml ampoules. The ampoules are sealed.

[0172] Option 3:

[0173] A pre-prepared reactor is loaded with 90.7 liters of water for injection at a temperature of 24°C. 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 (the process is then carried out with constant bubbling of the solution with nitrogen).

[0174] With the stirrer running (200-300 rpm), add 181.41 g of sodium disulfite to the reactor and stir for at least 10 minutes until completely dissolved. Then, add 9.07 kg (based on the main ingredient) of sodium chondroitin sulfate to the reactor in portions and stir for at least 60 minutes until completely dissolved.

[0175] Next, 45.35 g of methyl parahydroxybenzoate is added to the reactor, stirred for at least 20 minutes, and a sample is taken. The pH of the resulting solution is measured and, if necessary, adjusted 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 (containing 14 mg of elemental iron per 1 kg of sodium chondroitin sulfate, manufactured by Pfizer Inc., Germany) is added while stirring. The solution is then brought to the calculated volume (20 L) with water for injection and stirred for at least 15 minutes.

[0176] After analysis and adjustments (if necessary), the solution is sterilized and filtered and dispensed into 1 ml ampoules. Example 5. Preparation of tablets

[0177] Option 1: Tablet containing chondroitin sulfate and glucosamine hydrochloride.

[0178] The tablet formulation can be prepared as follows: 48.96 kg of sodium chondroitin sulfate, 48.96 kg of glucosamine hydrochloride, and 2.67 g of ferrous sulfate (containing 20 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: Dr. Paul Lohmani GmbH, Germany) are mixed in a drum mixer. The resulting mixture is molded and pressed, then dried to the required residual moisture content and calibrated. Then they are 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.

[0179] Option 2: A tablet containing chondroitin sulfate.

[0180] The composition in the form of a tablet can be prepared 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 Lohmani GmbH, Germany), calcium stearate - 1.29 kg; kollidon - 3.10 kg; povidone-KZO - 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 formed and pressed, then dried to the required residual moisture content and calibrated.

[0181] Option 3: Tablet containing chondroitin sulfate and glucosamine hydrochloride.

[0182] 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 Lohmani 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.

[0183] Example 6. Preparation of capsules

[0184] Option 1: Capsules containing 160 mg of sodium chondroitin sulfate per capsule.

[0185] The composition can be prepared as follows: 7.11 g of ferrous fumarate (containing 25 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: 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. The mixture is ground in a ball mill. 15 liters of distilled water are added to the resulting mixture, the mass is stirred, and 697.67 g of sodium dodecyl sulfate is added. The mass is stirred until a homogeneous consistency is achieved. The mixture is then granulated and dried at 36-40 °C, ground, and sieved through a 0.5 µm sieve. The granulate is mixed with 93.02 kg of sodium chondroitin sulfate and 1.16 kg of magnesium stearate.

[0186] Option 2: Capsules containing 200 mg of sodium chondroitin sulfate per capsule.

[0187] The composition can be prepared as follows: 8.52 g of ferrous fumarate (containing 30 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: 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. The mixture is ground in a ball mill. 18-20 liters of distilled water are added to the resulting mixture, the mass is stirred, and 557.36 g of sodium dodecyl sulfate is added. The mass is stirred until a homogeneous consistency is achieved. The mixture is then granulated and dried at 36-40 °C, ground, and sieved through a 0.6 µm sieve. The granulate is mixed with 92.89 kg of sodium chondroitin sulfate and 928.94 g of magnesium stearate.

[0188] Option 3: Capsules containing 180 mg of sodium chondroitin sulfate per capsule.

[0189] The composition can be prepared as follows: 10.43 g of ferrous fumarate (based on 37 mg of elemental iron per 1 kg of sodium chondroitin sulfate. Manufacturer: 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. The mixture is ground in a ball mill. 18-20 liters 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 achieved. The mixture is then granulated and dried at 36-40 °C, ground, and sieved 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.

[0190] Final quality control of the drugs in all described dosage forms was carried out using the methods described in the State Pharmacopoeias, regulatory documents, and informational and methodological documents. Several methods (titrimetric, colorimetric, and spectrometric) exist for the quantitative determination of elemental iron content. Spectrometric methods are the most sensitive (accurate). In this study, atomic absorption spectrometry (OPS 1.2.11.0005.18 SP RF) and inductively coupled plasma atomic emission spectrometry (OPS 1.2.1.1.0004.15 SP RF) were used.

[0191] The examples presented above demonstrate that the preparation of drugs can be implemented in various dosage forms using various methods and excipients that do not affect the final result, since the functional role of the agent for the treatment of arthrological diseases and the achievement of the stated 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.

[0192] Research

[0193] Animal studies were conducted to evaluate the therapeutic efficacy of the compounds described in this invention. The study compared six medications in different formulations. For each formulation, medications corresponding to one of the manufacturing variants were manufactured. Comparison medications were used for similar formulations, differing in composition but lacking iron.

[0194] Drugs participating in the study

[0195] The list of drugs studied is given in Table 1. Table 1

[0196] Dosage, duration of course, method of administration

[0197] In accordance with guidelines for studying the overall effectiveness of pharmacological agents, the minimum dose when studying side effects should be close to the therapeutic dose.

[0198] 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:

[0199] Table 2

[0200] Experimental groups

[0201] 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):

[0202] Table 3 Animals for research

[0203] The determination of the indicators was carried out on rabbits.

[0204] The experiments were performed on Chinchilla rabbits aged 12-14 months, weighing 2.7 ± 0.5 kg.

[0205] A randomization method was used to assign animals to groups. The absence of external signs of disease and homogeneity of body weight across groups (±10%) were considered criteria for randomization eligibility.

[0206] Quarantine

[0207] The quarantine period for all animals was 14 days. During this period, each animal was examined daily for behavior and general condition, and the animals were observed twice daily in their cages for morbidity and mortality.

[0208] Before the study began, animals meeting the inclusion criteria were randomly assigned to groups. Animals that did not meet the criteria were excluded from the study during the quarantine period.

[0209] Animal keeping

[0210] The animals were kept in accordance with the requirements of GOST R 53434-2009 from 02.12.2009 "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 corresponding to 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%. Lighting in the rooms was natural / artificial. A 12-hour lighting cycle was maintained in the animal holding rooms.

[0211] Observation period and recorded indicators

[0212] The observation period was 52 days.

[0213] Animals from groups A1, B1, B1, G1, D1, and E1 underwent destruction 30 days prior to the study by administering papain six times, at 5-day intervals, into the right knee joint at a dose of 50 mg per injection (1 ml of a 5% solution). Upon completion of the treatment course, animals from all groups were euthanized with an overdose of ether and sent for autopsy.

[0214] The animals' general condition was assessed through daily examinations. Weighing, rectal temperature measurements, and water and food intake were performed once every two weeks and after the end of the experiment.

[0215] Every 3 days, an ultrasound examination of the thickness of the articular cartilage of the knee joint and an assessment of knee joint pain were performed.

[0216] Every 5 days, the diameter of the destroyed joint was measured to assess swelling.

[0217] Methods of performance evaluation

[0218] Articular cartilage thickness test

[0219] Articular cartilage thickness in the rabbit knee joint was measured using ultrasound. Measurements were taken 31 days before the study and papain-induced knee joint destruction, on the first day of treatment with the inventive agents, then every 3 days throughout the course of treatment, and at the end of the study on day 52.

[0220] Data processing

[0221] After the study, all results were tabulated for each indicator and subgroup. The time, extent, and dynamics of complete and partial articular cartilage regeneration were assessed.

[0222] Results of the study of articular cartilage thickness

[0223] Gel dosage form

[0224] The studies were conducted on animals from Group 1 (G1). The results of the study are presented in Table 4. Table 4.

[0225] Group No. 1 (G1)

[0226] * 0 - 31 days before the start of the study and the onset of joint destruction by papain

[0227] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 1).

[0228] Ointment dosage form

[0229] The studies were conducted on animals from Group 2 (G2). The results are presented in Table 5.

[0230] Table 5.

[0231] Group No. 2 (G2)

[0232] The dynamics of changes in articular cartilage thickness are shown in the graph (Fig. 2). Lyophilisate for intramuscular administration.

[0233] The studies were conducted on animals from Group 3 (G3). The results are presented in Table 6.

[0234] Table 6.

[0235] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 3).

[0236] Solution for intramuscular administration.

[0237] The studies were conducted on animals from Group 4 (G4). The results are presented in Table 7.

[0238] Table 7.

[0239] O - 31 days before the start of the study and the beginning of joint destruction by papain

[0240] The dynamics of changes in articular cartilage thickness are shown in the graph (Fig. 4). Tablet dosage form

[0241] The studies were conducted on animals from Group 5 (G5). The study results are presented in Table 8.

[0242] Table 8.

[0243] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 5).

[0244] Encapsulated dosage form

[0245] The studies were conducted on animals from Group 6 (Gb). The results are presented in Table 9.

[0246] Table 9.

[0247] Group No. 6 (GB)

[0248] The dynamics of changes in the thickness of articular cartilage are shown in the graph (Fig. 6). Conclusion

[0249] The results of all studies are presented in Table 10.

[0250] Table 10.

[0251] Based on the results of studies across all dosage forms, a clear conclusion emerges regarding the significant advantages of the inventive agents over comparator drugs. The use of the claimed compositions results in a shorter treatment duration and more complete cartilage tissue regeneration. With the use of the inventive agents, treatment courses can be significantly shortened.

[0252] The formulations of the invention also demonstrated a significant increase in cartilage thickness. This conclusion is supported by the graphs showing the dynamics of cartilage thickness growth. Almost all graphs demonstrate that the agents of the invention begin to act from the very beginning of treatment. This effect is particularly noticeable in the graphs showing the dynamics of cartilage growth for the solution and lyophilisate (Figure 3 and Figure 4).

[0253] 31

[0254] CORRECTED SHEET (RULE 91)

Claims

CLAUSES OF THE INVENTION 1. A treatment for 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 claim 1, wherein 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 mass 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 based on the mass of sodium chondroitin sulfate.

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

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

12. The agent according to claim 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 claim 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 claim 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 claim 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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