Pharmaceutical composition for use in the treatment and regeneration of the musculoskeletal system, the pharmaceutical composition and the method of treatment with use thereof

Abstract

The invention relates to a pharmaceutical composition, a method of treatment utilizing thereof, and a pharmaceutical composition for use in the treatment of disease of the musculoskeletal system, which, as an active ingredient, comprises autologous platelet-rich plasma; a local anesthetic selected from lignocaine, ropivacaine, bupivacaine, benzocaine, chloroprocaine; an anti-edematous compound selected from betamethasone, triamcinolone, methylprednisolone, triamcinolone, methylprednisolone acetate; hyaluronic acid; somatotropin and strophanthin; wherein the pharmaceutical composition is intended to be administered in an effective dose to the treated target site of the musculoskeletal system of a subject, which is a mammal, more preferably a human.

Description

[0001] Pharmaceutical composition for use in the treatment and regeneration of the musculoskeletal system, the pharmaceutical composition and the method of treatment with use thereof

[0002] TECHNICAL FIELD

[0003] The object of the invention is a pharmaceutical composition for use in the treatment and regeneration of the musculoskeletal system, in particular changes caused by degenerative arthritis, the pharmaceutical composition and the method of treatment utilizing thereof.

[0004] STATE OF ART

[0005] Compositions for the regeneration of damage to the musculoskeletal system and their applications are known in the state of the art.

[0006] Document US8871199 discloses a method of improving tissue regeneration by obtaining platelets from a patient, preparing a platelet lysate, administering a hyperosmolar agent in an amount that induces a local inflammatory process, and then administering the platelet lysate to the site of tissue damage. Said composition may be administered during arthroscopy or percutaneously in an outpatient setting.

[0007] Document US20050100536 presents a method of producing a platelet-rich plasma composition, i.e. PRP, and its use in treating connective tissue damage. The method comprises determining the damaged tissue and then injecting the composition into the site of damage or its vicinity.

[0008] Document US20130243879 discloses a platelet-rich plasma composition, a method of its preparation and its use for treating connective tissue damage. The composition may contain contrast agents to facilitate monitoring of the target site of administration of the composition.

[0009] The publication (Rahimzadeh, 2016) indicates the potential use of a platelet-rich plasma composition with somatotropin (4 IU per injection) for the treatment of rheumatoid arthritis administered under ultrasound guidance. The document also discloses the possibility of using hyaluronic acid in a composition for the treatment of degenerative arthritis.

[0010] There are also known documents showing the effective action of homeopathic preparations such as Zeel T in the form of a series of 10 injections into joints with degenerative inflammation of the knee joint, which resulted in clinical improvement of the patients' health condition (Gottwald, 2000). Document PL426950A1 discloses a set of pharmaceutical compositions and a device for administering the set of pharmaceutical compositions, as well as a method of administering the set of compositions and use in the regeneration of the musculoskeletal system. The invention also discloses optimal concentrations of PRP in a composition with a concentration of analgesics and anti-edematous drugs. The composition includes platelet-rich plasma (PRP), hyaluronic acid, lignocaine, which is a local anesthetic, suspended in a physiological saline solution for injection. The document discloses the possibility of administering the composition to key points / core points , the so-called CP (Core Points), using ultrasound navigation before PRP administration in order to determine the exact point of administration at which the treatment will be most effective. CP are the result of spatial analyses and reflect disease cells. The aforementioned solution provides a composition for use in regenerative treatment using "nano-surgery and tissue bio-engineering in individual disease entities in the musculoskeletal system" in vivo (as an alternative to extensive surgical procedures in selected disease entities), reducing both: pain and the time it takes to regain physical fitness compared to standard PRP treatments and surgical procedures. However, despite the effects, the revealed effectiveness of the composition for the regeneration of diseased lesions ranged from 50 to 75% depending on the disease entity and the site of the diseased lesion. Additionally, despite the attempts, the assessment of pain complaints at specific time points after the administration of the composition still indicated that the patients experienced pain. Therefore, there is a need to find compositions that demonstrate higher effectiveness in reducing pain, increasing the range of joint movement after the procedure, and ensuring a shorter time to return to full mobility after the procedure.

[0011] Use of PRP (platelet-rich plasma) for the treatment of connective tissue injuries is known. PRP is most often administered in a surgical or outpatient setting. PRP is administered together with a local anesthetic, in particular lignocaine, ropivacaine, bupivacaine, benzocaine, chloroprocaine (Bausset, 2014) and an anti-edematous compound such as betamethasone, triamcinolone, methylprednisolone, triamcinolone, methylprednisolone acetate. However, despite the progress in the field of methods for the regeneration of the musculoskeletal system, there is still a need to develop compositions that will enable more effective treatment of patients suffering from musculoskeletal disorders such as injuries and rheumatoid arthritis.

[0012] There are also known 3D ultrasound examination techniques in diagnostics and treatment using Core Points assigned to a given segment of the musculoskeletal system. However, the state of the art lacks methods that ensure high repeatability of determining Core Points in patients suffering from different diseases and that take into account the etiology of the disease in determining Core Points.

[0013] Strophantin is a cardiac glycoside used to strengthen heart muscle contractions and stabilize heart rhythm. DISCLOSURE OF THE INVENTION

[0014] In light of the described state of the art, the aim of the present invention is to overcome the indicated inconveniences observed with the known compositions for the treatment of the musculoskeletal system, especially to ensure the acceleration of the regeneration process of the patient's musculoskeletal system. The inconveniences concern, among others, the feeling of moderate pain after the injection procedure of the composition, variable effectiveness in regeneration depending on the disease entity.

[0015] The aim of the present invention is to solve the technical problem of developing a composition having properties enabling higher efficiency of regeneration of the musculoskeletal system in comparison to compositions known in the state of the art and ensuring a faster return to mobility after the procedure while reducing pain.

[0016] The essence of the invention

[0017] The object of the invention is a pharmaceutical composition for use in the treatment and regeneration of diseases of the musculoskeletal system, which comprises as an active ingredient: autologous platelet-rich plasma concentrated from 0.5 to 15 times; a local anesthetic selected from lignocaine, ropivacaine, bupivacaine, benzocaine, chloroprocaine in an amount of 0.01 to 15% w / v; an anti- edematous compound selected from betamethasone, triamcinolone, methylprednisolone, triamcinolone, methylprednisolone acetate in an amount of 0.001 to 10% w / v; hyaluronic acid in an amount of 0.05 to 20% w / v; somatotropin 0.001% to 7 w / v; and strophanthin 1x10-5 % to 1% w / v; wherein the pharmaceutical composition is intended to be administered in an effective dose to the treated target site of the musculoskeletal system of a subject, which is a mammal, more preferably a human, wherein the disease of the musculoskeletal system is an inflammation, damage, trauma, degenerative change of the musculoskeletal system.

[0018] In the preferred pharmaceutical composition for use, the strophanthin is in the form of an extract from Strophantus combe.

[0019] In the preferred pharmaceutical composition for use, the local anesthetic is lignocaine.

[0020] In the preferred pharmaceutical composition for use, the anti-edematous compound is betamethasone.

[0021] The pharmaceutical composition for use preferably comprises: autologous platelet-rich plasma from 0.5 to 15 times concentrated, preferably 1 to 10 times concentrated; lignocaine 0.01 to 15% w / v, more preferably 0.1-0.2%. w / v; betamethasone 0.001 to 10% w / v, more preferably 0.05-1% w / v; hyaluronic acid 0.05 to 20% w / v, more preferably 0.1-5% w / v; somatotropin 0.001% do 7 w / v; strophanthin lxl0'5% to 1% w / v, more preferably 5xl0'5% to 0.1% w / v. The pharmaceutical composition for use preferably further comprises autologous stem cells of the treated subject, wherein preferably the stem cells are derived from adipose tissue, more preferably they are mesenchymal stem cells, more preferably the autologous stem cells of the treated subject are administered in an effective dose of 1-1000 thousand / ml, more preferably 35-750 thousand / ml.

[0022] In the preferred pharmaceutical composition for use, the disease of the musculoskeletal system affects a joint, more preferably a degenerative change in the joint caused by degenerative arthritis.

[0023] In the preferred pharmaceutical composition for use in the musculoskeletal disease, the disease is a spinal, wrist joint, elbow joint, shoulder joint, ankle joint, hip joint, knee joint, foot joint, metatarsal joint, Achilles tendon, coccygeal joint of the spinal segments disease, wherein preferably for (i) the spine disease includes a single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits at the lumbar, thoracic and cervical level, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord injury; (ii) wrist joint disease includes degenerative change in the elbow joint, Triangular Fibrocartilage Complex Injury, carpal tunnel syndrome, instability and damage to the ligaments of the wrist, Dupuytren's disease, hand joints, contractures of various etiologies, damage to the muscles and tendons in the wrist and hand, extensor and flexor tendinopathies, carpal tunnel syndrome, Guyon's canal syndrome, degenerative changes in the joints of the wrist and hand, joint hand contracture, hand and wrist post-traumatic soft tissue injuries, damage to the triangular cartilage; (iii) elbow joint disease includes: degenerative change in the elbow joint, ligaments and tendon damages in the elbow joint, contractures of various etiologies, muscles and tendons damages in the elbow joint, distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, ligament damage in the elbow joint; (iv) shoulder joint disease includes: degenerative changes in the ankle joint, subacromial conflict of different etiology, obliterative capsulitis of the shoulder joint, contractures of various etiologies, muscle and tendon injuries, obliterative inflammation of the capsular complex, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage; (v) ankle joint disease includes: degenerative changes in the ankle joint, instability and damage in the ligaments and tendons in the ankle joint, contractures of various etiologies, muscle and tendon damage, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon tendinopathy, extensor tendon tendinopathy, tibial tendon tendinopathy; (vi) hip joint disease includes: degenerative changes in the hip joint grade III and IV according to the K-L scale in patients qualifying for hip joint replacement and endoprosthesis implantation, acetabular-cephalic conflicts of the hip joint, contractures of various etiologies, muscle and tendon injuries, neurological syndromes, sciatica, CAM and PINCER acetabular conflict, degenerative and traumatic injuries in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, hip bursitis, piriformis syndrome, sciatic nerve neuropathy; (vii) knee joint disease includes: degenerative changes of grade III and IV according to the K-L Scale in members qualifying for knee joint replacement and endoprosthesis implantation, Patellofemoral pain syndrome, cruciate ligament of the knee joint rupture, contractures of various etiologies, only muscles and tendons, obliterative inflammation of the knee joint capsular complex, patellofemoral joint compression, contractual penalties of the lateral ligaments, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis.

[0024] Preferably, the pharmaceutical composition is administered to the target site, which is the spine, a wrist joint, an elbow joint, a shoulder joint, an ankle joint, a hip joint, a knee joint, a foot joint, a metatarsal joint, the Achilles tendon, coccygeal joints of the spinal segments.

[0025] In the preferred pharmaceutical composition for use in the musculoskeletal disease, the disease is a degenerative disease selected from the group consisting of: obliterative inflammation of the knee joint capsular complex, degenerative changes in the extensor apparatus, patellofemoral joint compression, lateral ligaments traumatic damage, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis, carpal tunnel syndrome, extensor and flexor tendons tendinopathies, obliterative inflammation of the capsular complex, Guyon's canal syndrome, degenerative changes in the wrist and hand joint, joint hand contracture, post-traumatic soft tissue injuries, triangular fibrocartilage injury and distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, ligament damage in the elbow joint, single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord damage, neurological syndromes (sciatica), CAM and PINCER acetabular conflict, obliterative inflammation of the capsular complex, degenerative and traumatic damages in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, bursitis of the hip joint, piriformis syndrome, sciatic nerve neuropathy, obliterative inflammation of the capsular complex, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage, axillary nerve entrapment, capsular-ligamentous complex damage, obliterative inflammation of the capsular complex, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon, extensor tendon, tibial tendon tendinopathy, carpal tunnel syndrome.

[0026] Preferably, the pharmaceutical composition for use is intended for administration to the target site by nanosurgery and bioengineering under ultrasound guidance, preferably by creating microincisions and microdelaminations in at least one Core Point.

[0027] Preferably, the pharmaceutical composition for use is administered to at least one, preferably two to several dozen Core Points at the target site.

[0028] The invention also relates to a pharmaceutical composition that comprises as an active ingredient autologous platelet-rich plasma in the amount of 0.01 to 15% w / v; local anesthetic selected from lignocaine, bupivacaine, bupivacaine, benzocaine, chloroprocaine in an amount of 0.001 to 10% w / v; anti-edematous compound selected from betamethasone, triamcinolone, methylprednisolone, triamcinolone, methylprednisolone acetate in the amount of 0.001 to 10% w / v; hyaluronic acid in the amount of 0.05 to 20% w / v; somatotropin in the amount of 0.001% to 7 w / v; and strophanthin in the amount of 1x10-5% to 1% w / v; wherein the pharmaceutical composition is intended for the treatment of diseases of the musculoskeletal system for local administration to the target site of treatment in a subject which is a mammal, more preferably a human; wherein preferably the disease of the musculoskeletal system is inflammation, damage, injury, degenerative change of the musculoskeletal system.

[0029] In the preferred pharmaceutical composition the strophanthin is in the form of an extract of Strophantus combe.

[0030] In the preferred pharmaceutical composition the local anesthetic is lignocaine.

[0031] In the preferred pharmaceutical composition the anti-edematous compound is betamethasone.

[0032] The pharmaceutical composition preferably comprises autologous platelet-rich plasma 0.5 to 15 times concentrated, preferably 1 to 10 times concentrated; lignocaine 0.01 to 15% w / v, more preferably 0.1-0.2%. w / v, betamethasone 0.001 to 10% w / v, more preferably 0.05-1% w / v, hyaluronic acid 0.05 to 20% w / v, more preferably 0.1-5% w / v, somatotropin 0.001% to 7 w / v, strophanthin lxl0'5% to 1% w / v, more preferably 5xl0'5% to 0.1% w / v.

[0033] The pharmaceutical composition preferably further comprises autologous stem cells of the subject, wherein preferably the stem cells are derived from adipose tissue, more preferably they are mesenchymal stem cells, more preferably autologous stem cells of the treated individual in an effective dose are administered in a concentration of 1-1000 thousand / ml, more preferably 35-750 thousand / ml.

[0034] The pharmaceutical composition is preferably intended for administration to the target site by nanosurgery and bioengineering under ultrasound guidance.

[0035] The pharmaceutical composition is preferably in liquid form.

[0036] The invention also relates to a method of treating and regenerating a musculoskeletal disease in a subject with a topically administered composition, wherein the pharmaceutical composition according to the invention is administered in an effective dose to the target site of the subject, which is a mammal, more preferably a human.

[0037] In a preferred method, the disease of the musculoskeletal system is an inflammation, damage, injury, or degenerative change of the musculoskeletal system, more preferably the disease of the musculoskeletal system affects a joint, more preferably a degenerative change of the joint caused by degenerative arthritis.

[0038] In a preferred method, the composition is administered to the target site to be treated by nanosurgery and bioengineering under ultrasound guidance.

[0039] In a preferred method, the composition is administered to the target site by nanosurgery and bioengineering under ultrasound guidance to create microincisions and microdissections in at least one Core Point.

[0040] In a preferred method, the composition is administered to at least one, preferably two to several dozen, most preferably two to twenty Core Points at the target site.

[0041] In a preferred method, the target site is spine, wrist joint, elbow joint, shoulder joint, ankle joint, hip joint, knee joint, foot joint, metatarsal joint, Achilles tendon, coccygeal joints of the spinal segments.

[0042] In a preferred method, the musculoskeletal disease is a disease of the spine, wrist joint, elbow joint, shoulder joint, ankle joint, hip joint, knee joint, foot joint, metatarsal joint, Achilles tendon, coccygeal joints of the spinal segments, wherein, preferably, for the (i) spine disease includes a single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits at the lumbar, thoracic and cervical level, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord injury; (ii) wrist joint disease includes degenerative change in the elbow joint, Triangular Fibrocartilage Complex Injury, carpal tunnel syndrome, instability and damage to the ligaments of the wrist, Dupuytren's disease, hand joints, contractures of various etiologies, damage to the muscles and tendons in the wrist and hand, extensor and flexor tendinopathies, carpal tunnel syndrome, Guyon's canal syndrome, degenerative changes in the joints of the wrist and hand, joint hand contracture, hand and wrist post-traumatic soft tissue injuries, damage to the triangular cartilage; (iii) elbow joint disease includes: degenerative change in the elbow joint, ligaments and tendon damages in the elbow joint, contractures of various etiologies, muscles and tendons damages in the elbow joint, distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, ligament damage in the elbow joint; (iv) shoulder joint disease includes: degenerative changes in the ankle joint, subacromial conflict of different etiology, obliterative capsulitis of the shoulder joint, contractures of various etiologies, muscle and tendon injuries, obliterative inflammation of the capsular complex, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage; (v) ankle joint disease includes: degenerative changes in the ankle joint, instability and damage in the ligaments and tendons in the ankle joint, contractures of various etiologies, muscle and tendon damage, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon tendinopathy, extensor tendon tendinopathy, tibial tendon tendinopathy; (vi) hip joint disease includes: degenerative changes in the hip joint grade III and IV according to the K-L Scale in patients qualifying for hip joint replacement and endoprosthesis implantation, acetabular-cephalic conflicts of the hip joint, contractures of various etiologies, muscle and tendon injuries, neurological syndromes, sciatica, CAM and PINCER acetabular conflict, degenerative and traumatic injuries in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, hip bursitis, piriformis syndrome, sciatic nerve neuropathy; (vii) knee joint disease includes: degenerative changes of grade III and IV according to the K-L scale in members qualifying for knee joint replacement and endoprosthesis implantation, Patellofemoral pain syndrome, cruciate ligament of the knee joint rupture, contractures of various etiologies, only muscles and tendons, obliterative inflammation of the knee joint capsular complex, patellofemoral joint compression, contractual penalties of the lateral ligaments, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis.

[0043] In a preferred method, the musculoskeletal disease is a degenerative change selected from the group consisting of: obliterative inflammation of the knee joint capsular complex, degenerative changes in the extensor apparatus, patellofemoral joint compression, lateral ligaments traumatic damage, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis, carpal tunnel syndrome, extensor and flexor tendons tendinopathies, obliterative inflammation of the capsular complex, Guyon's canal syndrome, degenerative changes in the wrist and hand joint, joint hand contracture, post-traumatic soft tissue injuries, triangular fibrocartilage injury and distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, ligament damage in the elbow joint, single- and multi-level discopathies with displacement and spinal stenosis without or with neurological deficits, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord damage, neurological syndromes (sciatica), CAM and PINCER acetabular conflict, obliterative inflammation of the capsular complex, degenerative and traumatic damages in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, bursitis of the hip joint, piriformis syndrome, sciatic nerve neuropathy, obliterative inflammation of the capsular complex, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage, axillary nerve entrapment, capsular-ligamentous complex damage, obliterative inflammation of the capsular complex, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon, extensor tendon, tibial tendon tendinopathy, carpal tunnel syndrome.

[0044] In the composition, betamethasone has a strong anti-inflammatory effect by reducing tissue edema and passive tissue hyperemia, and lidocaine causes local anesthesia. Thanks to the content of plateletrich plasma, the composition has a strong regenerative effect and enhances angiogenesis. Hyaluronic acid maintains the appropriate tissue pH for the regeneration process by locally increasing the pH at the site of administration. Hyaluronic acid is also a carrier for PRP and other substrates of the composition. The content of somatotropin stimulates tissues to produce somatomedin IgFl and IgF2, which enhance the process of growth and proliferation, and thus tissue healing. Strophantin stimulates the sodium-potassium pump, which regulates the concentration of Na+and K+in the extracellular matrix and in cells, increasing cell turgor. The effect of the strophanthin solution used according to the invention is caused by the active substance - strophanthin.

[0045] The pharmaceutical composition according to the invention, as demonstrated in the presented embodiments, has been successfully used for the treatment and regeneration of injuries and diseases of the musculoskeletal system as an alternative to surgical treatment.: i) hip joint replacement - endo- prosthesis implantation, ii) knee joint replacement - endo-prosthesis implantation, iii) spine diseases - discopathy and spinal stenosis at the lumbar, thoracic and cervical level, iv) acetabular-cephalic conflicts of the hip joint, v) knee joint patellofemoral impingement, vi) knee joint rupture of the cruciate ligament, vii) instability and ligament injuries and tendon injuries of the ankle joint, viii) subacromial impingement of various etiologies, ix) obliterative inflammation of the joint capsule of the shoulder joint, x) elbow joint ligament and tendon damage, xi) wrist triangular cartilage damage, xii) carpal tunnel syndrome, xiii) wrist instability and ligament damage, xiv) hand joints, xv) Dupuytren's disease, xvi) muscles and tendons in the musculoskeletal system damage, xvii) contractures of various etiologies in various segments of the musculoskeletal system.

[0046] The administered effective doses of the pharmaceutical composition according to the invention are selected by a specialist or physician depending on the advancement of the musculoskeletal system disease, the type of disease or the patient's condition, but most often they are in the range of 0.01- 200 ml, more preferably 0.05-50 ml, more preferably 0.5-45 ml, more preferably 1-40 ml of the administered composition per segment of the musculoskeletal system, i.e. the target site.

[0047] Compared to the compositions and non-surgical techniques for treating joints currently used in the world, the innovation also consists in combining the novel composition according to the invention with an adapted one to optimize its effectiveness by administering the composition to the joint using the method of nanosurgery and bioengineering treatment under ultrasound guidance, i.e. the NSBT method (NSBT, nanosurgery and bioengineering treatment underneath ultrasound guidance), which assumes the administration of the composition under ultrasound navigation to Core Points in a volume dependent on the size of the joint. Core Points (CP), are the result of spatial analyses and reflect the links in the development of the disease. For the purpose of description, the size of the joints is divided into small joints, which are: wrist joint, ankle joint, elbow joint, spine joints; and large joints, which are: knee joint, hip joint, shoulder joint. The Core Points to which the composition is administered correspond to the example points shown in PL426950A1, and are shown in FIG. 15- 22.

[0048] The produced compositions used autologous preparations, i.e. material obtained from the patient's blood and fat, which after appropriate processing and supplementation to the final composition were re-administered to the joint requiring such treatment.

[0049] The statistical significance of the treatment effect using the composition of the invention was analyzed using the Statistica 13.3 program. Due to the ordinal nature of the variables, non-parametric tests were used, i.e. the Kruskal-Wallis ANOVA test to compare the mean values between the four groups and post-hoc comparisons for the mean ranks of all pairs of groups. In multiple comparisons, the Bonferroni correction was applied to reduce the probability of making a type I error. The level of statistical significance was set at a=0.05.

[0050] Unexpectedly, it was found that by additionally using a strophanthin solution in the pharmaceutical composition according to the invention, a synergistic effect was achieved in the form of a significant reduction in pain, by reducing edematous changes caused by an excess of the intercellular matrix (p<0.001) during and after the procedures in which the compositions according to the invention were used for the treatment of degenerative changes in the joints. Moreover, the administration of the composition according to the invention resulted in a significantly (p<0.001) shorter time needed to return to daily activities after nanosurgery or bioengineering of the joints, including the knee, hip, wrist, spine, ankle, and shoulder affected by trauma. The synergistic effect of action was also observed for the improvement of the patient's range of motion, which was achieved in a shorter time (p<0.001) in each of the treated segments of the musculoskeletal system mentioned above. The demonstrated synergy also concerned the visualized reduction of tissue edema in ultrasound images observed even within 1 hour after the administration of the composition.

[0051] An additional effect and synergy of action was observed in the case of a composition additionally containing mesenchymal stem cells collected from adipose tissue (p<0.001).

[0052] BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Example implementations of the invention are presented in the figures of the drawing. FIG. 1-7 present a comparison of USG (ultrasound) images of different patients, where each figure corresponds to one segment of the musculoskeletal system, and the individual letters (A, B, C, D) denote patients in whom the image was taken at two time points: 1 - before the administration of a given composition (Via, V2a, V3a, V4a, Vlb, V2b, V3b or V4b) and 2 - i.e. 7 days after the administration of this composition, where both time points 1 and 2 refer to the same patient and the same treated joint. The arrows indicate the area of edematous changes, decreasing after the administration of the composition according to the invention.

[0054] FIG. 1 Ultrasound images (USG) of the spine joints of the patients. Patient 1 (discopathy L4 / 5) - composition Vlb: Al - before administration, A2 - after administration to the spinous process and the attachment of the deep fascia of the muscles of the spine joint; Patient 2 (discopathy C6 / 7) - composition V2b: Bl - before administration, B2 - after administration to the attachment of the deep fascia of the muscles of the spine C joint; Patient 3 - (stenosis of the L4 / 5 canal) composition V3b: Cl-before administration, C2-after administration to the superficial and deep layer of the fascial attachment of the spinous process, the intermediate layer and the muscle layer of the back muscles, the spine joint; Patient 4 (discopathy L2 / 3)-composition V4b: Dl-before administration and D2-after administration to the spinous process and muscle attachments at the level of the lumbar zone of the spine joint.

[0055] FIG. 2 Ultrasound photographs of the elbow joint of different patients. Patient 5 (tendovaginitis LHBT)- composition Via: Al before administration and A2 after administration to the tendon of the long head of biceps of the elbow joint; Patient 6 (injury to the supraspinatus tendon with subacromial impingement)- composition V2a: Bl before administration, B2 after administration to the following structures of the elbow joint: lateral part of the anterior capsular complex, medial fascia of the long head of biceps tendon, fascia of the brachial muscle, medial part of the anterior capsular complex; Patient 7 (tear of the common flexor attachment of golfer's elbow)- composition V3a: Cl before administration and C2 after administration to the elbow joint. Patient 8 (tear of extensor tendon attachments - tennis elbow) - composition V4a: DI before administration and D2 after administration to the extensor attachment of the lateral epicondyle of the humerus of the elbow joint.

[0056] FIG. 3 Ultrasound photographs of the hip joint of patients. Patient 9 (degenerative changes in the hip joint)-composition Vlb: Al before administration and A2 after administration to the femoral head and capsular complex of the hip joint; Patient 10 (degenerative changes in the labrum of the hip joint)-composition V2b: Bl before administration and B2 after administration to the labrum of the hip joint; Patient 11 (CAM-type acetabular impingement of the hip joint)-composition V3b: Cl before administration and C2 after administration to the following structures of the hip joint: lateral capsular complex, central capsular complex, lateral capsular complex, central capsular complex; Patient 12 (Pincer-type acetabular impingement of the hip joint) - composition V4b: DI before administration and D2 after administration of the composition to the proximal attachment of the capsular complex of the hip joint.

[0057] FIG. 4 Ultrasound photographs of the knee joint of patients. Patient 13 (degenerative changes in the knee joint) - composition Vlb: Al before administration and A2 after administration into the patellar recess of the knee joint; Patient 14 (patellofemoral impingement of the knee joint) - composition V2b: Bl before administration and B2 after administration into the patellar ligament of the knee joint; Patient 15 (ligamentous damage - MCL of the knee joint) - composition V3b: Cl before administration and C2 after administration of the composition to the following structures of the knee joint: deep fascia of the quadriceps aponeurosis in the proximal part, deep boundary plane of the patellar ligament, proximal part of the course of the MCL (tibial collateral ligament), deep fascia of the patellar ligament; Patient 16 (the medial meniscus damage of the knee joint) - composition V4b: DI before administration and D2 after administration to the paracapsular attachment of the medial meniscus of the knee joint. FIG. 5 Ultrasound photographs of the shoulder joint of patients. Patient 17 (deltoid injury / subacromial conflict) - composition Vlb: Al before administration and A2 after administration to the shoulder muscle; Patient 18 (subacromial bursitis with injury to the supraspinatus tendon - subacromial conflict) - composition V2b: Bl before administration and B2 after administration to the following structures of the shoulder joint: deep fascia of the deltoid muscle in the anterolateral part, rotator cuff, lower boundary layer of the rotator cuff in the anterior part of the joint from the joint side, upper boundary layer for the rotator cuff in the posterolateral part of the joint - from the bursa side; Patient 19 (supraspinatus tendon injury - subacromial conflict) - composition V3b: Cl before administration of the composition and C2 after administration to the rotator cuff of the shoulder joint; Patient 20 (subacromial bursitis, subacromial conflict) - composition V4b: DI before administration of the composition and D2 after administration to the anterosuperior recess of the knee joint bursa.

[0058] FIG. 6 Ultrasound photographs of the ankle joint of patients. Patient 21 (posttraumatic tarsal tunnel syndrome) - composition Via: Al before administration and A2 after administration into the tarsal tunnel of the ankle joint; Patient 22 (traumatic injury of the triquetral ligament) - composition V2a: Bl before administration and B2 after administration to the following structures of the ankle joint: capsular complex of the ankle joint - course in the medial part, external outline of the talus, deep layer of the anterior tibiotalolar ligament; Patient 23 (traumatic injury of the talonavicular joint) - composition V3a: Cl before administration of the composition and C2 after administration into the talonavel j oint; Patient 24 (traumatic injury to the capsular-ligamentous complex) - composition V4a: DI before administration and D2 after administration to the proximal attachment of the anterior talofibular ligament (AFTL) of the ankle joint.

[0059] FIG. 7 Ultrasound images of the wrist joint of patients. Patient 25 (degenerative changes in the CMC joint) - composition Via: Al before administration and A3 after administration to the carpometacarpal joint (CMC); Patient 26 (degenerative changes of the PIP joints) - composition V2a: Bl before administration and B2 after administration to the proximal interphalangeal joint (PIP); Patient 27 (degenerative changes of the DIP joints) - composition V3a: Cl before administration and C2 after administration to the distal interphalangeal joint (DIP); Patient 28 (degenerative changes of the PIP joint) - composition V4a: DI before administration and D2 after administration to the volar plate of the proximal interphalangeal joint (PIP).

[0060] FIG. 8-14 graphically present the results of the statistical analysis of the pain assessment made by patients on the VAS scale (A-B) and the remaining parameters (E, F, G) for the compositions administered in the treatment of the selected musculoskeletal system disorders. A before treatment; B immediately after administration; C after 1 hour after administration; D after 7 days after administration; E time to full recovery after the procedure; F improvement in the range of motion from the administration of the composition in days; G effectiveness of the treatment after the composition was used. FIG. 8-14 concern:

[0061] FIG. 8 results of statistical analysis of the treatment of spinal disorders with Vlb-V4b compositions;

[0062] FIG. 9 results of statistical analysis of the treatment of wrist disorders with Vla-V4a compositions;

[0063] FIG. 10 results of statistical analysis of the treatment of elbow joint diseases with Vla-V4a compositions;

[0064] FIG. 11 results of statistical analysis of the treatment of shoulder joint diseases with Vlb-V4b compositions;

[0065] FIG. 12 results of statistical analysis of the treatment of ankle joint diseases with Vlb-V4b compositions;

[0066] FIG. 13 results of statistical analysis of the treatment of hip joint diseases with the Vlb-V4b composition;

[0067] FIG. 14 results of statistical analysis of the treatment of knee joint diseases with compositions Vlb- V4.

[0068] FIG. 15-22 show ultrasound images of the musculoskeletal system elements before and after the administration of the V3a or V3b composition with the indication of Core Points. The arrows indicate the edematous area within a given Core Point. FIG. 15-22 show:

[0069] FIG. 15 foot joints and Achilles tendon. A ankle joint, B tarsal joint - longitudinal section, C foot - cross-section, D Achilles tendon - longitudinal section;

[0070] FIG. 16 wrist and metacarpal joints. A wrist - longitudinal section dorsal side, B wrist - longitudinal section palmar side, C wrist - longitudinal section palmar side, D wrist palmar side - longitudinal projection, E wrist - transverse section palmar side, F lateral compartment of the wrist - longitudinal projection, G wrist - longitudinal projection dorsal side, H hand - transverse section;

[0071] FIG. 17 elbowjoint. A cross section of the anterior compartment of the joint, B lateral compartment longitudinal projection, C medial compartment - longitudinal projection, D posterior compartment - longitudinal projection, E groove of the ulnar nerve;

[0072] FIG. 18 shoulder joint and acromioclavicular joint. A - longitudinal projection of the rotator cuff, B - transverse projection of the rotator cuff, C - longitudinal projection of the rotator cuff, D - rotator cuff in the posterolateral compartment, E - anterior central part with the tendon of the long head of the biceps muscle, F - acromioclavicular joint; FIG. 19 ankle joint. A longitudinal section of the ankle joint - dorsal side, B longitudinal section of the ankle joint - medial side, C longitudinal section of the ankle joint - lateral side, D anterior crosssection of the ankle joint compartment;

[0073] FIG. 20 hip joint. A longitudinal projection, B - transverse projection, C lateral region - longitudinal projection, D iliac crest region, E lateral compartment at the level of the femoral neck;

[0074] FIG. 21 knee joint. A longitudinal projection - quadriceps aponeurosis zone, B longitudinal projection - patellar ligament zone, C medial compartment longitudinal projection, D lateral compartment longitudinal projection, E central compartment - transverse projection at the level of the intercondylar groove, F central compartment - transverse projection at the level of the patellar ligament;

[0075] FIG. 22 spinal joint. Transverse projection on the spinous process.

[0076] The publications cited in the description and the references given therein are hereby incorporated by reference in their entirety. The following examples illustrate the invention without limiting it in any way.

[0077] EXAMPLES OF EMBODIMENTS OF THE INVENTION

[0078] The following examples are provided solely for the purpose of illustrating the invention and explaining individual aspects thereof, and are not intended to be limitative and should not be construed as encompassing its entire scope, which is defined by the appended claims.

[0079] When the examples refer to "Dil. D4, Dil. D7, Dil. D9" the number following the letter "D" refers to the number of successive dilutions of the homeopathic medicine in a ratio of 1 : 10 of the original concentration of the homeopathic medicine, where "Dil. D4" refers to 4 successive dilutions of 1 : 10 (finally 1 : 10-4), "Dil. D7" refers to 7 successive dilutions of 1: 10 (finally 10-7), "Dil. D9" refers to 9 successive dilutions of 1 : 10 (finally 10-9) of the original concentration of the homeopathic medicine. When the examples refer to "strophanthin solution", this refers to the homeopathic medicine called Strophantus Comp, with the PZN number (German Pharma-Zentral-Nummer) 01752239, containing in 1 ml the following active ingredients: Aurum metallicum (metallic gold) Dil. D9 0.1 g, Stibium metallicum (metallic antimony) Dil. D7 0.1 g, Strophanthus kombe e semine ferm 35b Dil. D4 0.1 g, as well as other ingredients such as: sodium chloride, sodium bicarbonate, water for injection, milk protein (from lactose). The strophanthin solution was standardized to contain 0.001% w / v strophanthin in the extract, but the invention is not limited to this concentration.

[0080] When the examples refer to "somatropin solution", this refers to Norditropin NordiFlex with the authorization number 25575, which is a solution for injection containing the active substance 6.7 mg of somatropin in 1 ml of solution and the following excipients: mannitol, histidine, pol oxamer 188, phenol, water for injections, hydrochloric acid (for pH adjustment) and sodium hydroxide (for pH adjustment), but may also refer to other drugs or medicinal products in the appropriate concentration, e.g. Omnitrope or another product.

[0081] When the examples refer to "lignocaine solution" this refers to any authorized medicinal product containing lignocaine / lidocaine.

[0082] When the examples refer to "betamethasone solution", this refers to the medicinal product Diprophos (license number 01216) containing the active substances of: 6.43 mg of betamethasone dipropionate (Betamethasoni dipropionas) which corresponds to 5 mg of betamethasone, and 2.63 mg of betamethasone sodium phosphate (Betamethasoni natrii phosphas) which corresponds to 2 mg of betamethasone in 1 ml of solution, and excipients: Disodium phosphate dihydrate or disodium phosphate anhydrous, Sodium chloride, Disodium edetate, Polysorbate 80, Benzyl alcohol (E 1519) (9mg / ml), Methyl parahydroxybenzoate (E 218), Propyl parahydroxybenzoate (E 216), sodium carboxymethylcellulose, macrogol, hydrochloric acid (for pH adjustment), water for injections, but may also apply to other drugs or medicinal products in the appropriate concentration containing betamethasone.

[0083] When the examples refer to "micro-incisions", this refers to an ultrasound-guided nano-surgical procedure that replicates surgical techniques by cutting the joint capsule complex or other anatomical structure, e.g. tendon sheath, fascial compartment, etc. in a specific shape and using 0.4 - 0.8 mm needles or nano-tools.

[0084] When the examples refer to "micro-delaminations", this refers to a nano-surgical procedure guided by ultrasound, which reflects surgical techniques and is performed by administering fluid to a specific anatomical tissue compartment in a volume specified for a given condition, i.e. in such a way that the tissue layers become separated (no more adhered).

[0085] When the examples refer to degenerative changes according to the Kallgran-Lawrence (K-L) scale, this refers to a scale that represents the advancement of radiological changes in degenerative joint disease. This scale is presented in a four-point scale, described by Roman numerals I-IV, i.e. changes I (minimal) according to K-L mean the presence of small osteophytes in the radiological image, i.e. changes II (mild) according to K-L mean the presence of medium-sized osteophytes in the radiological image, i.e. Ill (moderate) K-L changes indicate the presence of large osteophytes and narrowing of the joint space in the radiological image, i.e. IV (marked) K-L changes indicate the presence of very large osteophytes and a very narrowed or invisible joint space in the radiological image, whereby changes III and IV according to K-L are advanced degenerative changes that are currently treated surgically, and changes I and II according to K-L are changes that are not treated surgically.

[0086] Example 1 Preparation of a comparative and test compositions for administration to joints The comparative composition Via was prepared as described in the patent application PL426950A1 and supplemented with hyaluronic acid. In the composition with PL426950A1 the concentration of hyaluronic acid was not fully disclosed and for the comparative studies hyaluronic acid was used at a concentration of 0.225%, i.e. the concentration corresponding to the tested compositions.

[0087] For the purpose of conducting research in large and small joints, two types of compositions were produced for small joints - designated with the extension "a" and for large joints designated with the extension "b". The amount of active substance administered in the prepared portion was the same, but the final preparations differed in volume - so that the volume of the administered preparation was adapted to the size of the joint.

[0088] To prepare solution A, lignocaine solution, betamethasone solution, hyaluronic acid solution were placed in a sterile test tube and supplemented with physiological saline solution, with the volumes and concentrations for the individual compositions Via and Vlb being presented in Tab. 1. Somatotropin was also added to compositions V2a and Vlb, somatotropin solution and strophanthin solution were also added to compositions V3a and V3b, and stem cell suspension (solution C) was also added to compositions V4a and V4b, with the volumes and concentrations for the individual compositions Via and Vlb being presented in Tab. 1.

[0089] Both the stem cells and platelet-rich plasma used in the compositions were produced from the patient's own material, and therefore the compositions administered were autologous preparations.

[0090] The techniques for producing platelet-rich plasma as well as stem cells from adipose tissue are known both in medicine and in orthopedics. The techniques for obtaining these preparations presented below can therefore be replaced by others that serve the same purpose.

[0091] In order to prepare solution B containing platelet-rich plasma, 25 ml of peripheral blood was collected from the treated patient under sterile conditions and placed in a centrifuge tube. The blood was centrifuged in a centrifuge at a speed of 80,000xg for 8 minutes. The result of centrifugation was the separation of plasma (upper layer) from blood (lower layer) and obtaining 10 ml of plasma with a platelet density 2-10 times higher than in the patient's peripheral blood.

[0092] In order to prepare the compositions Via, Via, V3a, Vlb, Vlb, V3b, solution A and B were mixed together in a ratio of 1 : 1 to form the final compositions as indicated in Tab. 1 as "final composition" .

[0093] To prepare compositions V4a and V4b, solution C was first prepared. For this purpose, 15 ml of adipose tissue was collected from the treated patient's abdominal area using a syringe, transferred to centrifuge tubes and centrifuged at 2500 RPM for 4 min. Biological material was obtained in the form of 3.5 ml of a suspension of mesenchymal stem cells. The number of cells was counted using a counting chamber - the cell density was 700 thousand cells per 1 ml of suspension. To prepare the final concentrations of compositions V4a and V4b, the volume of solution C specified in Tab. 1 was mixed with solution A. Then, the resulting solution was mixed in an equal volume with solution B. Tab. 1 The proportions used to prepare the compositions of the invention. "Preparation of the composition" means the volume of solution of a given concentration that must be mixed together to produce the final compositions. "Final composition" means the final concentration of active substances and / or cells in the compositions used in the tests. Example 2 Method of determining Core Points for administration of the composition of the invention

[0094] To determine the Core Points for the administration of the composition according to the invention, magnetic resonance imaging, X-rays, joint nanoscopies and ultrasound examinations of the pathologically changed elements of the musculoskeletal system were first performed. Core Points were determined on the basis of repeated analyses of ultrasound images in specific disease entities and in their specific stages, taking into account the pathomechanisms of the disease development. In the next stage, based on the obtained data, the number and diameters of inflammatory foci within the joint were determined. The criterion for designating an area as a Core Point was the determination of the disturbance of the fibrillar structure of the examined structure with the deviation of echogenicity (hypo- or hyperdense) of the examined area in comparison to the normal (healthy) tissue. In the next step, a spatial analysis of the inflammatory and degeneratively changed structures of the joint complex (joint and tendon -muscle structures) was performed by constructing a 3D model of Core Points responsible for the development of the disease and they were arranged in the chain of pathomechanisms in which a given disease entity was formed. This analysis consisted in marking the position of Core Points in the 3D module and introducing the aforementioned module into one or more schemes of procedure inscribed in geometric figures in the shape of a flat figure, i.e. a trapezoid, rectangle, triangle, circle, hexagon, polygon, segment, as well as spatial figures, i.e. a cone, cylinder, sphere, cuboid, prism. The 3D model of Core Points was made to cover the entire volume of the inflammatory and degenerative focus while maintaining the margin of tissue elements directly adjacent to the diseased zone. The indicated Core Points are the places to which the composition according to the invention is administered in accordance with the method of regeneration and treatment using the nanosurgery and biotechnology method under ultrasound control. The Core Points determined for the individual segments of the musculoskeletal system are shown in FIG. 15- 22 and marked with numbers from 1 to 171 and described anatomically in Tab. 2. Tab. 2 Core Points of individual elements of the musculoskeletal system to which the compositions according to the invention were administered. _

[0095] In the next stage, the optimal number of punctures (micro-incisions and micro-dissections) into the diseased area was determined in order to administer the composition. The number of punctures depends on the number of inflammation points in the periarticular compartment designated by Core Points in terms of periarticular adhesions, as well as their extent and the thickness of the tissue layer.

[0096] Example 3 Administration of compositions to small and large joints. Treatment of musculoskeletal diseases by introducing the composition using nanosurgery and bioengineering method under ultrasound guidance (NSBT)

[0097] The studies were conducted on a group of patients with diagnosed degenerative changes. The compositions prepared as in Example 1, Via, V2a, V3a, V4a were administered to small joints, i.e. the hand, wrist, ankle joint, and the compositions Vlb, V2b, V3b, V4b were administered to large joints, i.e. the knee, hip, shoulder and spine joint.

[0098] In all examples, the composition being tested was administered to the patient as set forth in Example 3, every 7 days at 3 time points on day 1, 7, 14, for a single dose per day, for a total of 3 doses of the composition. A microdevice containing a needle was used to administer the composition. The compositions were administered under ultrasound guidance in a volume of 1 ml-40 ml to one segment of the musculoskeletal system, i.e. the target site (the volume administered to the joint depended on the size of the target site and the area of the Core Point(s) affected by inflammation), inserting the needle at an angle of 30-70° to the skin. The compositions were administered in sterile outpatient conditions using the nanosurgery and bioengineering method under ultrasound control, i.e. the NSBT method, by administering the compositions to at least one, several, usually not exceeding 14-20 Core Points. The studies were conducted on a group of 33 patients for each studied segment of the musculoskeletal system. The composition was administered with a needle, for example, in the following manner into the layer of the superficial subcutaneous fascia, and then into the layers beneath it, i.e., successively: the deep fascia zone, the muscle structure, the bone structure layer - the outer cortical layer.

[0099] The average pain intensity on the VAS scale was measured before the administration of the composition, 1 hour after the administration of the composition, 7 days after the first administration of the composition, after the end of treatment (21 days after the first administration), and the reduction of pain complaints measured 2 months after the first administration of the composition. On the VAS scale: 0 means no pain, from 1 to 3 - mild pain, from 4 to 6 - moderate pain, while from 7 starts strong pain, which progresses to very strong up to point 10, which is unbearable pain. The obtained results from the treatment for the tested compositions for the given disease entities within a given joint were presented. The obtained results were statistically calculated for a given group of patients and presented as a median along with statistical significance regarding the pain scale (VAS).

[0100] In the ultrasound USG examination, the time of edematous changes subsided after the administration of the composition was measured. The increase in joint mobility was measured step by step after each administration of the composition. When assessing joint mobility, 100% range of motion means a return to a healthy state without any deficits in both everyday activities and sports activities.

[0101] Comparison of treatment results and changes in physiological parameters and pain sensations in treated patients for the tested compositions are presented in the tables below (Tab. 3-9). Nonparametric tests, i.e. Kruskal-Wallis ANOVA, were used for statistical analysis. Bonferroni correction was used for multiple comparisons. The statistical significance level was set at a=.05. The use of compositions V3a, V4a, in relation to Via and V2a, as well as V3b, V4b in relation to Vlb and V2b, was compared. Statistical analyses of pain intensity in the VAS scale and changes in the treated patients were presented in the form of median (lst-3rd quartile).

[0102] Example 4 The impact of the tested compositions on the regeneration of spine joints

[0103] The spinal diseases treated with the above-mentioned preparations concerned injuries, inflammations and degenerative changes of the spine, in particular: single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits at the lumbar, thoracic and cervical level, intervertebral disc diseases, muscle pain with limited efficiency and functionality, spine instability, spinal cord damage.

[0104] TAB. 3. Comparison of treatment results for the tested compositions (spine)

[0105] The results of pain intensity in the treated patients are shown in FIG. 8 A-D, and the results concerning the influence of the compositions on the improvement of the physiological parameters of the patients are shown in FIG. 8E-F. It has been shown that the effectiveness of the treatment of spinal diseases with the compositions according to the invention is higher Fig. 8 G.

[0106] Example 5 The impact of the tested compositions on the regeneration of wrist joints

[0107] Diseases of the wrist joints treated with the above-mentioned preparations concerned injuries, inflammations and degenerative changes, in particular: degenerative changes in the elbow joint, patients qualifying for surgical treatment of damage to the triangular cartilage of the wrist, patients qualifying for surgical treatment of carpal tunnel syndrome, patients qualifying for surgical treatment of instability and ligament injuries of the wrist, patients qualifying for surgical treatment of Dupuytren's disease, patients qualifying for surgical treatment of the hand joints, contractures of various etiologies, muscle and tendon damage, tendinopathies of the extensor and flexor tendons, carpal tunnel syndrome, Guyon's canal syndrome, degenerative changes in the wrist and hand joints, hand joint contractures, post-traumatic soft tissue damage, damage to the triangular cartilage, carpal tunnel syndrome.

[0108] TAB. 4 Comparison of treatment results for the tested compositions (wrist). The results of pain intensity in the treated patients are shown in FIG. 9 A-D, and the results of the influence of the composition on the improvement of the physiological parameters of the treated patients are shown in FIG. 9 E-F. It has been shown that the effectiveness of the treatment of wrist diseases with the compositions according to the invention is higher Fig. 9 G.

[0109] Example 6 The influence of the tested compositions on the regeneration of the elbow joint

[0110] The compositions were administered as shown in Example 3, at 3 time points. The diseases of the elbow joint that were treated with the above-mentioned preparations concerned injuries, inflammations and degenerative changes, in particular they concerned: degenerative changes in the elbow joint, patients qualifying for surgical treatment of ligament injuries and tendon damages in the elbow joint, contractures of various etiologies, muscle and tendon injuries, distal radioulnar joint instability, common extensor and flexor attachment (tennis elbow and golfer's elbow) tendinopathy, capsular complex of various etiologies, ligament damage in the elbow joint. Very good results were observed after just one administration of the composition in the case of diseases such as golfer's elbow and tennis elbow, however, for the treatment of other diseases, the compositions were used at 3 time points.

[0111] TAB. 5 Comparison of treatment results for the tested compositions (elbow joint).

[0112] The results of pain intensity in the treated patients are shown in FIG. 10 A-D, the results concerning the influence of the composition on the improvement of the physiological parameters of the patients are shown in FIG. 10 E. It has been shown that the effectiveness of the treatment of diseases of the elbow joint with the compositions according to the invention is higher Fig. 10F.

[0113] Example 7 The impact of the tested compositions on the regeneration of degenerative changes in the shoulder joint

[0114] Diseases of the shoulder joint treated with the above-mentioned preparations concerned injuries, inflammations and degenerative changes, in particular: degenerative changes in the ankle joint, patients qualifying for surgical treatment of subacromial impingement of various etiologies, patients qualifying for surgical treatment of obliterative capsulitis of the shoulder joint, contractures of various etiologies, muscle and tendon injuries, obliterative inflammation of the capsular complex, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial impingement of various etiologies, post- traumatic damage and degenerative changes in the acromioclavicular and sternoclavicular joints, damage to the tendons of the biceps brachii, axillary nerve entrapment, damage to the capsular- ligamentous complex.

[0115] TAB. 6. Comparison of treatment results for the tested compositions (shoulder joint).

[0116] The results of pain intensity in the treated patients are shown in FIG. 11 A-D, and the results concerning the influence of the composition on the improvement of the physiological parameters of the patients are shown in FIG. 11 E-F. It has been shown that the effectiveness of the treatment of diseases of the shoulder joint with the compositions according to the invention is higher Fig. 11 G.

[0117] Example 8 The impact of the tested compositions on the regeneration of degenerative changes in the ankle joint

[0118] Diseases of the ankle joint that were treated with the above-mentioned preparations included injuries, inflammations and degenerative changes, in particular: degenerative changes in the ankle joint, patients qualifying for surgical treatment of instability and ligament damages and tendon damages of the ankle joint, contractures of various etiologies, muscle and tendon injuries, anterior and posterior ankle joint impingement, degenerative changes of the tarsal joints, foot, Achilles tendon tendinopathy, extensor tendon tendinopathy, tibial tendon tendinopathy.

[0119] The results of pain intensity in the treated patients are shown in FIG. 12A-D, and the results regarding the effect of the composition on the improvement of the physiological parameters of the patients are shown in FIG. 12E-F. It has been shown that the efficacy of the treatment of ankle joint diseases with the compositions according to the invention is higher Fig. 12G.

[0120] Example 9 The influence of the tested compositions on the regeneration of degenerative changes in the hip joint Diseases of the hip joint treated with the above-mentioned preparations concerned injuries, inflammations and degenerative changes, in particular: degenerative changes of the hip joint grade III and IV according to the K-L Scale, patients qualifying for hip joint replacement and endoprosthesis implantation, patients qualifying for surgical treatment of acetabular-cephalic conflicts of the hip joint, contractures of various etiologies, muscle and tendon injuries, neurological syndromes (sciatica), CAM and PINCER femoroacetabular impingement, degenerative and traumatic damage in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, hip joint bursitis, piriformis syndrome, sciatic nerve neuropathy.

[0121] Tab. 8 Comparison of treatment results for the tested compositions (hip joint).

[0122] The results of pain intensity are shown in FIG. 13A-D, and the results concerning the influence of the compositions on the improvement of physiological parameters of patients are shown in FIG. 13E-F. It has been shown that the effectiveness of the treatment of hip joint diseases with the compositions according to the invention is higher Fig. 13 G.

[0123] Example 10 The impact of the tested compositions on the regeneration of degenerative changes in the knee joint

[0124] The influence of the tested compositions was conducted on a group of individuals with diagnosed degenerative changes in the knee joint over the age of 61, who were qualified for surgical treatment using knee joint endoprosthesis.

[0125] The diseases of the knee joint treated with the above-mentioned preparations concerned injuries, inflammations and degenerative changes, in particular: degenerative changes of grade III and IV according to the K-L Scale in patients qualifying for knee joint replacement and endoprosthesis implantation, patients qualifying for surgical treatment of patellofemoral pain syndrome, patients qualifying for surgical treatment of cruciate ligament of the knee joint rupture, contractures of various etiologies, muscle and tendon injuries, obliterative inflammation of the knee joint capsular complex, degenerative changes in the extensor apparatus, patellofemoral joint compression, lateral ligaments traumatic damage, anterior cruciate ligament damage, posterior cruciate ligament damage, meniscus of the knee joint damage, knee joint arthrosis.

[0126] Tab. 9 Comparison of treatment results for the tested compositions (knee joint).

[0127] The results of pain intensity are illustrated in FIG. 14 A-D, and the results concerning the influence of the compositions on the improvement of the physiological parameters of the patients are illustrated in FIG. 14 E-F. It has been shown that the effectiveness of the treatment of knee joint diseases with the compositions according to the invention is higher Fig. 14 G. The results obtained using various tested compositions indicate higher effectiveness of the new compositions according to the invention V3 and V4 than those known from the state of the art, i.e. with the addition of somatotropin and strophanthin, very good effects were achieved by adding autologous stem cells from fat cells.

[0128] The solution according to the invention overcomes the disadvantages of the state of the art by providing a composition with a more powerful, synergistic effect in terms of regeneration and healing in relation to those presented in the state of the art. Strophantin is a strong cardiac glycoside that has not been used in the treatment of musculoskeletal diseases. Strophantin stimulates the sodiumpotassium pump, which regulates the concentration of Na+and K+in the extracellular matrix and in cells, increasing cell turgor, and its use in combination of the invention shows an unexpected regenerative effect. The unexpected use of strophanthin in combination with somatotropin, hyaluronic acid and platelet-rich plasma (compositions V3a and V3b) turned out to statistically significantly enhance the regeneration and treatment process of injuries and diseases of the musculoskeletal system. The combination of strophanthin with somatotropin and stem cells, hyaluronic acid and platelet-rich plasma (compositions V4a and V4b) even more strongly enhanced the regenerative and healing effect.

[0129] The composition was compared to compositions known in the art, enabling the selective selection of appropriate active substances and their preferred concentrations of betamethasone, hyaluronic acid, lignocaine, PRP, and the addition of somatotropin and strophanthin showed a synergistic effect of the composition according to the invention for the regeneration and for the treatment of the musculoskeletal system.

[0130] LITERATURE:

[0131] Bausset O, Magalon J, Giraudo L, Louis ML, Serratrice N, Frere C, Magalon G, Dignat-George F, Sabatier F. Impact of local anaesthetics and needle calibres used for painless PRP injections on platelet functionality. Muscles Ligaments Tendons J. 2014 May 8;4(1): 18-23. PMID: 24932442; PMCID: PMC4049644.

[0132] Levy DM, Petersen KA, Scalley Vaught M, Christian DR, Cole BJ. Injections for Knee Osteoarthritis: Corticosteroids, Viscosuplementation, Platelet-Rich Plasma, and Autologous Stem Cells. Arthroscopy. 2018 May; 34(5): 1730-1743. doi: 10.1016 / j.arthro.2018.02.022. Epub 2018 Apr 12. PMID: 29656808.

[0133] Radice Marco; Pastorello Andrea; Pavesio Alessandra; Callegaro Lanfranco. 2004. Injectable hyaluronic acid derivative with pharmaceuticals / cells. US6699471B2.

[0134] Mishra Allan. 2005. Compositions and minimally invasive methods for treating incomplete tissue repair. US20050100536.

[0135] Mishra Allan Kumar.2013. Platelet rich plasma formulations and use thereof. US20130243879 Rahimzadeh P, Imani F, Faiz SH, Alebouyeh MR, Azad-Ehyaei D, Bahari L, Memarian A, Kim KH. Adding Intra-Articular Growth Hormone to Platelet Rich Plasma under Ultrasound Guidance in Knee Osteoarthritis: A Comparative Double-Blind Clinical Trial. Anesth Pain Med. 2016 Oct 19;6(6):e41719. doi: 10.5812 / aapm.41719. PMID: 28975078; PMCID: PMC5560632.

[0136] Wasilczyk C. 2018. Pharmaceutical composition and set of compositions, device for administration of the set of pharmaceutical compositions, method of administration of the set of compositions and use in regeneration of the locomotor system. PL426950A1.

[0137] Gottwald R. and Weiser M. Treatment of osteoarthritis of the knee with Zeel T. International Journal for Biomedical Research and Therapy. 2000. Medicina Biologica.

Claims

CLAIMS1. A pharmaceutical composition for use in the treatment of diseases of the musculoskeletal system, which, as an active ingredient, comprises: autologous platelet-rich plasma concentrated from 0.5 to 15 times; a local anesthetic selected from lignocaine, ropivacaine, bupivacaine, benzocaine, chloroprocaine in an amount from 0.01 to 15% w / v; an anti-edematous compound selected from betamethasone, triamcinolone, methylprednisolone, triamcinolone, methylprednisolone acetate in an amount of 0.001 to 10% w / v; hyaluronic acid in an amount of 0.05 to 20% w / v; somatotropin 0.001% to 7% w / v; and strophanthin 1x10'5% to 1% w / v; wherein the pharmaceutical composition is for administeration in an effective dose to the treated target site of the musculoskeletal system of a subject, which is a mammal, more preferably a human, wherein the disease of the musculoskeletal system is an inflammation, damage, trauma, degenerative change of the musculoskeletal system.

2. The pharmaceutical composition for use according to claim 1, characterized in that strophanthin is in the form of an extract of Strophantus combe.

3. The pharmaceutical composition for use according to claim 1 -2, characterized in that the local anesthetic is lignocaine.

4. Pharmaceutical composition for use according to claims 1-3, characterized in that the anti- edematous compound is betamethasone.

5. The pharmaceutical composition for use according to claims 1-4, characterized in that the composition comprises: autologous platelet-rich plasma from 0.5 to 15 times concentrated, preferably 1 to 10 times concentrated; lignocaine 0.01 to 15% w / v, more preferably 0.1 -0.2%. w / v, betamethasone 0.001 to 10% w / v, more preferably 0.05-1% w / v, hyaluronic acid 0.05 to 20% w / v, more preferably 0.1-5% w / v, somatotropin 0.001% do 7% w / v, strophanthin lxl0'5% to 1% w / v, more preferably 5xl0'5% to 0.1% w / v.

6. The pharmaceutical composition for use according to claims 1-5, characterized in that the composition further comprises autologous stem cells of the treated subject, wherein, preferably, the stem cells are derived from adipose tissue, more preferably they are mesenchymal stem cells.

7. The pharmaceutical composition for use according to claim 6, characterized in that the autologous stem cells of the treated subject in an effective dose are administered at the concentration of 1-1000 thousand / ml, more preferably 35-750 thousand / ml.

8. The pharmaceutical composition for use according to claims 1-7, characterized in that the disease of the musculoskeletal system is a joint, more preferably a degenerative change in the joint caused by degenerative arthritis.

9. The pharmaceutical composition for use according to claims 1-8, characterized in that the musculoskeletal disease is a disease of the spine, wrist joint, elbow joint, shoulder joint, ankle joint, hip joint, knee joint, foot joint, metatarsal joint, Achilles tendon, coccygeal joints of the spinal segments, wherein preferably(i) the spine disease includes a single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits at the lumbar, thoracic and cervical level, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord injury;(ii) wrist joint disease includes degenerative change in the elbow joint, Triangular Fibrocartilage Complex Injury, carpal tunnel syndrome, instability and damage to the ligaments of the wrist, Dupuytren's disease, hand joints, contractures of various etiologies, damage to the muscles and tendons in the wrist and hand, extensor and flexor tendinopathies, carpal tunnel syndrome, Guyon's canal syndrome, degenerative changes in the joints of the wrist and hand, joint hand contracture, hand and wrist post-traumatic soft tissue injuries, damage to the triangular cartilage;(iii) elbow joint disease includes: degenerative change in the elbow joint, ligaments and tendon damages in the elbow joint, contractures of various etiologies, muscles and tendons damages in the elbow joint, distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, ligament damage in the elbow joint;(iv) shoulder joint disease includes: degenerative changes in the ankle joint, subacromial conflict of different etiology, obliterative capsulitis of the shoulder joint, contractures of various etiologies, muscle and tendon injuries, obliterative inflammation of the capsular complex, distalattachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage;(v) ankle joint disease includes: degenerative changes in the ankle joint, instability and damage in the ligaments and tendons in the ankle joint, contractures of various etiologies, muscle and tendon damage, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon tendinopathy, extensor tendon tendinopathy, tibial tendon tendinopathy;(vi) hip joint disease includes: degenerative changes in the hip joint grade III and IV according to the K-L Scale in patients qualifying for hip joint replacement and endoprosthesis implantation, acetabular-cephalic conflicts of the hip joint, contractures of various etiologies, muscle and tendon injuries, neurological syndromes, sciatica, CAM and PINCER acetabular conflict, degenerative and traumatic injuries in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, hip bursitis, piriformis syndrome, sciatic nerve neuropathy;(vii) knee joint disease includes: degenerative changes of grade III and IV according to the K-L scale in members qualifying for knee joint replacement and endoprosthesis implantation, Patellof emoral pain syndrome, cruciate ligament of the knee joint rupture, contractures of various etiologies, only muscles and tendons, obliterative inflammation of the knee joint capsular complex, patellof emoral joint compression, contractual penalties of the lateral ligaments, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis.

10. The pharmaceutical composition for use according to claims 1 -9, characterized in that the target site is a spine, a wristjoint, an elbow joint, a shoulder joint, an ankle joint, a hip joint, a knee joint, a foot joint, a metatarsal joint, the Achilles tendon, coccygeal joints of the spinal segments.

11. The pharmaceutical composition for use according to claims 1-10, characterized in that the disease of the musculoskeletal system is a degenerative change selected from the group consisting of: obliterative inflammation of the knee joint capsular complex, degenerative changes in the extensor apparatus, patellof emoral joint compression, lateral ligaments traumatic damage, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis, carpal tunnel syndrome, extensor and flexor tendons tendinopathies, obliterative inflammation of the capsular complex, Guyon's canal syndrome, degenerative changes in the wristand hand joint, joint hand contracture, post-traumatic soft tissue injuries, triangular fibrocartilage injury and distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, ligament damage in the elbow joint, single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord damage, neurological syndromes (sciatica), CAM and PINCER acetabular conflict, obliterative inflammation of the capsular complex, degenerative and traumatic damages in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, bursitis of the hip joint, piriformis syndrome, sciatic nerve neuropathy, obliterative inflammation of the capsular complex, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage, axillary nerve entrapment, capsular-ligamentous complex damage, obliterative inflammation of the capsular complex, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon, extensor tendon, tibial tendon tendinopathy, carpal tunnel syndrome.

12. The pharmaceutical composition for use according to claims 1-11, characterized in that the composition is intended for administration to a target site by nanosurgery and bioengineering method under ultrasound guidance, preferably by creating micro-incisions and micro-dissections in at least one Core Point.

13. The pharmaceutical composition for use according to claims 1-12, characterized in that the composition is administered to at least one, preferably two to several dozen Core Points in the target site.

14. A pharmaceutical composition characterized in that the composition comprises as an active ingredient autologous platelet-rich plasma in the amount of 0.01 to 15% w / v; a local anesthetic selected from lignocaine, bupivacaine, bupivacaine, benzocaine, chloroprocaine in an amount of 0.001 to 10% w / v; an anti-edematous compound selected from betamethasone, triamcinolone, methylprednisolone, triamcinolone, methylprednisolone acetate in the amount of 0.001 to 10% w / v;hyaluronic acid in the amount of 0.05 to 20% w / v; somatotropin in the amount of 0.001% to 7% w / v; and strophanthin in the amount of lxl0'5% to 1% w / v; wherein the pharmaceutical composition is for the treatment of diseases of the musculoskeletal system for local administration to the target site of treatment in a subject which is a mammal, more preferably a human; wherein, preferably, the disease of the musculoskeletal system is inflammation, damage, injury, degenerative change of the musculoskeletal system.

15. The pharmaceutical composition according to claim 14, characterized in that the strophanthin is in the form of an extract of Strophantus combe.

16. The pharmaceutical composition according to claims 14-15, characterized in that the local anesthetic is lignocaine.

17. The pharmaceutical composition according to claims 14-16, characterized in that the anti- edematous compound is betamethasone.

18. The pharmaceutical composition according to claims 14-17, characterized in that the composition comprises autologous platelet-rich plasma 0.5 to 15 times concentrated, preferably 1 to 10 times concentrated; lignocaine 0.01 to 15% w / v, more preferably 0.1 -0.2%. w / v, betamethasone 0.001 to 10% w / v, more preferably 0.05-1% w / v, hyaluronic acid 0.05 to 20% w / v, more preferably 0.1-5% w / v, somatotropin 0.001% to 7% w / v, strophanthin lxl0'5% to 1% w / v, more preferably 5xl0'5% to 0.1% w / v.

19. A pharmaceutical composition according to claims 14-18, characterized in that the composition further comprises autologous stem cells of the treated subject, wherein, preferably, the stem cells are derived from adipose tissue, more preferably they are mesenchymal stem cells.

20. The pharmaceutical composition according to claims 14-18, characterized in that the autologous stem cells of the treated subject in an effective dose are administered at the concentration of 1-1000 thousand / ml, more preferably 35-750 thousand / ml.

21. The pharmaceutical composition according to claims 14-20, characterized in that the composition is intended for administration to a target site by nanosurgery and bioengineering method under ultrasound guidance.

22. The pharmaceutical composition according to claims 14-21, characterized in that the composition is in liquid form.

23. A method of treating a musculoskeletal disease in a subject with a composition for topical administration, wherein the pharmaceutical composition according to claims 14-22 is administered in an effective dose to the target site of the subject, which is a mammal, more preferably a human.

24. The method according to claim 23, wherein the disease of the musculoskeletal system is inflammation, damage, injury, degenerative change of the musculoskeletal system, more preferably the disease of the musculoskeletal system concerns a joint, more preferably a degenerative change of the joint caused by degenerative arthritis.

25. The method according to claims 23-24, wherein the composition is administered to the treatment target site by nanosurgery and bioengineering method under ultrasound guidance.

26. The method according to claims 23-25, characterized in that the composition is administered to the target site by nanosurgery and bioengineering method under ultrasound guidance to create micro-incisions and micro-delaminations in at least one Core Point.

27. The method according to claims 23-26, wherein the composition is administered to at least one Core Point, preferably two to several dozen, most preferably two to twenty Core Points at the target site.

28. The method according to claims 23-27, wherein the target site is the spine, the wrist joint, the elbow joint, the shoulder joint, the ankle joint, the hip joint, the knee joint, the foot joint, the metatarsal joint, the Achilles tendon, coccygeal joints of the spine sections.

29. The method according to claims 23-28, wherein the musculoskeletal disease is a disease of the spine, wristjoint, elbowjoint, shoulder joint, anklejoint, hip joint, knee joint, footjoint, metatarsal joint, Achilles tendon, coccygeal joints of the spine sections, wherein preferably:(i) the spine disease includes a single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits at the lumbar, thoracic and cervical level, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord injury;(ii) wrist joint disease includes degenerative change in the elbow joint, Triangular Fibrocartilage Complex Injury, carpal tunnel syndrome, instability and damage to the ligaments of the wrist, Dupuytren's disease, hand joints, contractures of various etiologies, damage to the musclesand tendons in the wrist and hand, extensor and flexor tendinopathies, carpal tunnel syndrome, Guyon's canal syndrome, degenerative changes in the joints of the wrist and hand, joint hand contracture, hand and wrist post-traumatic soft tissue injuries, damage to the triangular cartilage;(iii) elbow joint disease includes: degenerative change in the elbow joint, ligaments and tendon damages in the elbow joint, contractures of various etiologies, muscles and tendons damages in the elbow joint, distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, ligament damage in the elbow joint;(iv) shoulder joint disease includes: degenerative changes in the ankle joint, subacromial conflict of different etiology, obliterative capsulitis of the shoulder joint, contractures of various etiologies, muscle and tendon injuries, obliterative inflammation of the capsular complex, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage;(v) ankle joint disease includes: degenerative changes in the ankle joint, instability and damage in the ligaments and tendons in the ankle joint, contractures of various etiologies, muscle and tendon damage, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon tendinopathy, extensor tendon tendinopathy, tibial tendon tendinopathy;(vi) hip joint disease includes: degenerative changes in the hip joint grade III and IV according to the K-L Scale in patients qualifying for hip joint replacement and endoprosthesis implantation, acetabular-cephalic conflicts of the hip joint, contractures of various etiologies, muscle and tendon injuries, neurological syndromes, sciatica, CAM and PINCER acetabular conflict, degenerative and traumatic injuries in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, hip bursitis, piriformis syndrome, sciatic nerve neuropathy;(vii) knee joint disease includes: degenerative changes of grade III and IV according to the K-L scale in members qualifying for knee joint replacement and endoprosthesis implantation, Patellof emoral pain syndrome, cruciate ligament of the knee joint rupture, contractures of various etiologies, only muscles and tendons, obliterative inflammation of the knee joint capsular complex, patellof emoral joint compression, contractual penalties of the lateral ligaments, anterior cruciateligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis.

30. The method according to claims 23-29, wherein the disease of the musculoskeletal system is a degenerative change selected from the group consisting of: obliterative inflammation of the knee joint capsular complex, degenerative changes in the extensor apparatus, patellofemoral joint compression, lateral ligaments traumatic damage, anterior cruciate ligament damage, posterior cruciate ligament damage, knee joint meniscus damage, knee joint arthrosis, carpal tunnel syndrome, extensor and flexor tendons tendinopathies, obliterative inflammation of the capsular complex, Guyon's canal syndrome, degenerative changes in the wrist and hand joint, joint hand contracture, post-traumatic soft tissue injuries, triangular fibrocartilage injury and distal radioulnar joint instability, common extensor and flexor attachment (tennis and golfer's elbow) tendinopathy, capsular complex of various etiologies, distal attachment of the biceps and triceps tendon tendinopathy, muscle and tendon syndromes of the arm and forearm, radial nerve in the lateral septum entrapment, interosseous nerve in arcade of Froshe entrapment, median nerve under the biceps tendon entrapment, ligament damage in the elbow joint, single- and multi-level discopathies with displacement and spinal stenosis (or without) or with neurological deficits, intervertebral disc disease, spinal muscle pain with limited efficiency and functionality, spinal instability, spinal cord damage, neurological syndromes (sciatica), CAM and PINCER acetabular conflict, obliterative inflammation of the capsular complex, degenerative and traumatic damages in the hip joint girdle muscles, deep gluteal syndrome, hip joint arthrosis, femoral nerve under the inguinal ligament entrapment, inguinal ligament syndrome, adductor syndrome, bursitis of the hip joint, piriformis syndrome, sciatic nerve neuropathy, obliterative inflammation of the capsular complex, subacromial bursitis, damage and degenerative changes in the rotator cuff, subacromial conflict of different etiology, posttraumatic damage and degenerative change in the acromioclavicular and sternoclavicular joints, biceps tendons damage, axillary nerve entrapment, capsular-ligamentous complex damage, obliterative inflammation of the capsular complex, anterior and posterior ankle joint conflict, degenerative changes in the tarsal joint, foot, Achilles tendon, extensor tendon, tibial tendon tendinopathy, carpal tunnel syndrome.

Images