Instructions for use of the liquid prosthesis Versan Fluid for the treatment of joints

Active physical activity does not go unnoticed. Sooner or later, the joints remind themselves of pain, limited mobility, and interfere with leading a normal lifestyle. If arthrosis develops, you will have to forget about sports forever. This was the case before – before the advent of intra-articular liquid endoprostheses. The drugs effectively eliminate unpleasant symptoms and stop degenerative processes. The only problem is which of the many to choose? Let's consider imported endoprostheses "Synvisk" (USA), "Versan Fluid" and "Noltrexin" made in Switzerland.

Brief description of the drug

Versan Fluid is a synovial fluid prosthesis with pronounced anti-inflammatory, analgesic and restorative properties. The drug is recommended for the treatment of acute and chronic osteoarthritis. Injections are made directly into the joint, the medicine relieves discomfort, restores normal mobility, and prevents further destruction of cartilage tissue.

ATX code

M09AX01 – Hyaluronic acid

Tradename

Versan Fluid

International nonproprietary name

Hyaluronic acid

Pharmacological group

Means that replace synovial and tear fluid.

Release form and packaging

The Swiss-made drug, which has undergone clinical trials in Russia and has received approval for intensive care, is available in the form of a clear, colorless liquid for injection , packaged in disposable plastic syringes with a volume of 2.5 ml.

Each syringe is packaged in a plastic contour cell and a cardboard box, which contains detailed instructions for use in Russian. Needles are not included and must be purchased separately.

Packaging of the drug Versan Fluid

Compound

The main active component of the drug is hyaluronic acid . Each syringe contains 25 mg of purified sodium hyaluronate solution. In addition to this, the solution for injection includes:

• disodium phosphate dodecahydrate;
• sodium chloride;
• sodium dihydrogen phosphate dihydrate;
• sterile purified water.

Manufacturer

Valentis AG, Switzerland

Benefits of dietary supplements

Complex No. 7, like other drugs of the brand, meet its Gold Standard. For SOLGAR, impeccable quality is the main criterion in its work.

The company has its own scientific center where research and development is carried out. Only fresh raw materials that meet strict state standards are used.

All components of the exclusive Gold Standard system:

• High-quality products - raw material suppliers provide certificates, data from all inspections, and this is a mandatory requirement.
• With its own research and development center, the brand develops cutting-edge innovations and not only uses classic technologies.
• Quality control – more than 130 different tests are used to control a set of parameters. Only products that meet advanced standards receive the Solgar Gold Label.
• Deep water purification – SOLGAR uses an advanced water purification system that operates by reverse osmosis type.
• Modern ventilation - using HEPA filters that filter 99.9% of polluting particles present in the air.
• Cleanliness - after the release of each new batch, the equipment is disassembled into parts, disinfected and only then used again.
• KOSHER and Halal certified – these indicate the highest production standards.
• Vegetarian capsules - the Solgar brand was one of the first to use them on the world market.
• No allergens in the composition - gluten, salt, sugar, dairy products, dyes, etc.
• Branded packaging - dark bottles that protect additives from fluctuations in humidity, temperature, and bright sunlight.

But the main advantage of the dietary supplement is its effectiveness, which reviews of Solgar for joints speak better than any advertisement.

Pharmacodynamics: mechanism of action and effect

The main active component of the injection solution is purified hyaluronic acid . It is an important component of tissues and intra-articular fluid. Its quality depends on sodium hyaluronate: saturation, viscosity. With a deficiency of acid, the synovial fluid thins out and the joint does not receive the necessary lubrication. When moving, its parts rub against each other, deforming the cartilage tissue. Every movement causes pain and inflammation occurs. The internal cavities are filled with effusion, and swelling forms in the joint area.

The hyaluronic acid contained in the composition (molecular weight 650000~1200000 Da) is extracted from microorganisms. This product is intended for single use. Hyaluronic acid is a natural polysaccharide that is an important structural element of the skin, subcutaneous and connective tissue (for example, synovial fluid). Hyaluronic acid, found in all living organisms, is identical and has a high level of biocompatibility. Each milliliter of the drug contains 10 mg of sodium hyaluronate diluted in saline solution.

Versan Fluid replenishes the lack of synovial fluid

In an effort to reduce the load and reduce pain, the patient sharply limits physical activity. This has the opposite effect. Without receiving the necessary load, joint tissues atrophy, and the production of synovial fluid decreases. The result may be irreversible deformation of the joint, requiring urgent surgery and replacement of the affected area with a permanent prosthesis.

Application of liquid synovial fluid prosthesis Versan Fluid:

• increases the viscosity and elasticity of the joint synovium;
• improves mobility and shock-absorbing properties of the musculoskeletal system;
• reduces abrasion of cartilage tissue;
• prevents the development of arthrosis and other serious destructive joint disorders.

Pharmacokinetics

The injection is made directly into the joint, sodium hyaluronate immediately enters the tissue and immediately begins to act. The active component is distributed in the synovial fluid within 2 hours, the maximum concentration of the substance in the blood is observed after 4 hours.

The acid is completely metabolized in the liver and excreted from the body in the urine within 24 hours.

Sodium hyaluronate does not have a negative effect on internal organs, the component does not accumulate in the body. The medicine is non-toxic and belongs to the low-hazard category.

Compound

The main active ingredients of the Solgar NO.7 complex:

• BOSWELLIA SERRATA extract (plant);
• Type II collagen (without denaturation).

Both components are patented by the brand and have an effect on mediators that trigger inflammatory processes. These mediators are always present in tissues during osteoarthritis, rheumatoid arthritis, and increased physical activity.

They stop the inflammatory process and improve overall well-being. Turmeric, red pepper, and ginger warm the joints, improve their mobility, and eliminate stiffness.

Other excipients - vitamin C, alba powder.

Indications for use

Synovial fluid replacement is an effective and safe solution for joints. When used in doses, the drug is capable of:

• reduce pain during movement and at rest;
• improve the quantity and quality of synovial fluid, preventing deformation of cartilage tissue;
• increase range of motion;
• restore normal mobility to the affected joint;
• prevent internal swelling.

Versan Fluid is prescribed for degenerative changes in joints

Injections are given only as prescribed by a doctor; self-medication is excluded. Hyaluronic acid injections are recommended for:

• osteoarthritis of the hip and knee joint;
• treatment of arthrosis accompanied by effusion;
• eliminating the consequences of injuries;
• recovery after joint surgery.

The drug is indicated in ophthalmology and is used to expand the anterior chamber or separate tissues, etc. (during operations on the anterior and posterior segments of the eye), examination of the retina during and after surgery, and laser therapy (adjuvant).

Indications for use are described in detail in the instructions. During a therapeutic course, it is not recommended to use similar drugs simultaneously with Versan. It is possible to use gels and ointments for external applications; a one-time use of non-steroidal anti-inflammatory drugs will help relieve severe pain.

What to choose

We have three imported drugs in front of us - one American and two Swiss. They all come with approximately the same instructions for use, look very similar, and are designed for the treatment of arthrosis of the knee, hip and other large joints. If you don’t understand deeply, you can buy any of them at random, guided by the rule “an imported drug will not let you down.”

In fact, behind similar descriptions and characteristics, completely different liquid endoprostheses are hidden.

• By choosing Versan Fluid, you will be forced to go again and again to an orthopedist or sports traumatologist for a “new portion” (3 injections every 6 months, that is, 12 injections in 2 years).
• With Synvisk, the number of injections can be reduced to three once a year - that is, 6 injections in 2 years.
• With Noltrexin, it is enough to take a course only once every two years, while for many, only 1-2 injections in 2 years are enough!

One thing is obvious. Before choosing a liquid endoprosthesis, check its molecular weight and composition. This is much more important than beautiful packaging or a well-promoted brand.

Contraindications for Versan Fluid injections

Solution for injection is not recommended for use when:

• autoimmune diseases;
• hypersensitivity to the components of the drug;
• infectious and bacterial lesions of the skin in the injection area.

The medicine also has indirect contraindications. Elderly people, children, adolescents and patients with various chronic diseases should be treated under the constant supervision of a doctor. Injections can be given to pregnant women if the effect of therapy exceeds the possible risk. Nursing mothers can use the medicine, but milk will have to be expressed and discarded during treatment. You can resume feeding after completing the therapeutic course.

In case of hemorrhage into the joint cavity, Versan Fluid injections are contraindicated

Instructions for use: method and dosage

• Injections are placed directly into the joint.
• The injection must be given by a doctor or nurse, because with self-administration there is a high risk of complications.
• The standard course includes 1 injection per week . After 7 days, the injection is repeated, a total of 3 injections are included in the course .
• If several joints need to be restored, injections are given to each area separately.

will need a thin disposable needle 18–25 G. The syringe is removed from the package so that its sterility is not compromised. If the drug was stored in the refrigerator, it can be warmed in the palms of your hands to room temperature. The fluid is injected slowly and carefully so that the patient does not experience pain. It is important to prevent damage to soft tissue.

During the therapy period, 3 syringes are used, 1 syringe every week, by injection into the affected joint of an adult patient. The fluid is intended for injection into the joint. The dosage and injection time are determined depending on the symptoms experienced by the patient. The entire contents of the syringe are injected in one dose; reuse of the remainder is prohibited.

During the injection, the patient should lie in a comfortable position. After the injection, he needs complete rest for 24 hours. If a limb is swollen, red, and painful, you can apply an ice pack to the affected joint.

During the course of treatment, the patient should avoid increased physical activity. A low-calorie diet with plenty of vegetables, fruits and other sources of natural fiber is recommended. It is necessary to give up alcohol and smoking. It has been observed that patients with normal weight who are not obese tolerate injections more easily, and the effectiveness of therapy increases.

You can repeat the course after 6 months. Usually, after 3 injections, a lasting therapeutic effect is achieved, the patient feels better, motor activity increases, and the risk of further deformation of the cartilage tissue is significantly reduced. In the intervals between injections, you can use strengthening gels and ointments, drink vitamin complexes with calcium and collagen.

Versan Fluid injections are performed directly into the joint cavity

Osteoarthritis of the knee joint

Osteoarthritis (OA) is the most common disease of synovial joints, caused by the action of biological and mechanical factors that upset the balance between the processes of degradation and synthesis of chodrocytes, extracellular matrix of articular cartilage and subchondral bone, which are the main cause of chronic pain syndrome, causing gait disturbances, disability and significant deterioration in the quality of life of patients. Osteoarthritis occurs predominantly in 65-85% of people in the older age group (over 65-65 years old). The general trend towards an increase in the proportion of older people in the population is accompanied by an increase in the prevalence of osteoarthritis, significant financial costs for its treatment and disability of patients, which determines the high socio-economic significance of this problem.

There are predispositions to the development of OA, which can be divided into modifiable and non-modifiable. Modifiable factors include: obesity, injury, disruption of the biomechanics of movements in a particular joint, habitual overload of the joints. Non-modifiable risk factors for development include: age, gender, heredity, race, congenital diseases, endocrine and metabolic disorders.

There are two forms of OA: idiopathic (when the exact cause of the disease is unknown) and secondary (when the cause is known).

The development of osteoarthritis always begins with pathological microscopic changes in cartilage tissues, which are not clinically manifested, while the period of subclinical manifestations can vary in duration - from 2 to 6 years. Cartilage tissue is damaged under the influence of mechanical or metabolic changes, it becomes thinner, with the formation of ulcers. Subsequently, the meniscus, ligamentous apparatus, periarticular bursa and proliferation of adjacent bone structures occur in the process. The narrowing of the joint space is accompanied by a decrease in the production of synovial fluid, friction of the articular surfaces and additional secondary destruction of cartilage tissue.

Inflammatory markers (cytokines, tumor necrosis factor) contribute to the appearance of pain. At the early stage of OA, interleukins 1.6 (IL-1.6), tumor necrosis factor-a (TNF-a) increase the synthesis of serum CRP and amyloid A. In the later stages of OA, the presence of synovitis correlates with both plasma CRP and the level of IL-6 in synovial fluid. In addition, the intensity of pain in gonarthrosis increases with increasing levels of serum CRP, TNF-a and IL-6.

In addition, blood circulation in the joint and adjacent tissues is simultaneously impaired, which leads to the development of secondary osteoporosis. Reflex muscle disorders occur around the joint, which create an additional mechanism for the formation of pain and limitation of mobility.

In turn, a decrease in motor activity in the joint leads to a decrease in the production of synovial fluid in it, which provides nutrition to the cartilage tissue and the removal of metabolic products from the joint cavity. A “vicious circle of osteoarthritis” is formed - a decrease in the production of synovial fluid increases the degree of damage to cartilage tissue.

Treatment of patients with OA includes a complex of measures consisting of a physical rehabilitation program (load limitation, correction of orthopedic disorders, physical therapy regimens), drugs with anti-inflammatory activity and drugs aimed at reducing pain and slowing down structural damage in joint tissues (SYSADOA - Symptomatic slow acting drugs for osteoarthritis). Of great importance is the impact on the metabolism of cartilage tissue in order to restore the balance between the load and the reparative capabilities of chondrocytes. For this purpose, slow-acting symptom-modifying or neuroprotective drugs are used. Currently, a large number of international and national recommendations for the treatment of OA have been proposed. According to these recommendations, in addition to the general principles of managing patients with OA, which include educational programs for weight loss and aerobic exercise, the prescription of not only paracetamol, NSAIDs, glucosamine sulfate and chondroitin sulfate, but also intra-articular administration of hyaluronic acid and topical glucocorticoids is indicated. In recent years, hyaluronic acid (HA) preparations, having a minimal risk of systemic side effects, have found widespread use in OA of the knee joints. Intra-articular therapy using GLA derivatives is approved by the world's professional rheumatology and orthopedic organizations as a symptomatic treatment for patients under 65 years of age who have not responded to non-pharmacologic treatments and simple analgesics or who have contraindications to nonsteroidal anti-inflammatory drug (NSAID) therapy (ACR, 2000, 2012 ; OARSI, 2010; EULAR 2003, ESCEO 2014).

So what is hyaluronic acid and through what mechanisms does it act on the disease?

Hyaluronan is a biological fluid that occurs in synovial fluid and is quite ubiquitous throughout the body. Hyaluronan is a polyanionic (negatively charged) polysaccharide, also known as glycosaminoglycan, which consists of alternating units of N-acetylglucosamine and sodium glucuronate molecules. The length of such a polysaccharide chain can reach 12 thousand disaccharide units, and the molecular weight is 4-6 million daltons. Biosynthesis of hyaluronan occurs on the inner surface of the cell membrane of fibroblastic differential cells with the participation of hyaluronan synthase (HAS). As the concentration of polysaccharides increases (above the saturation point), the long chains begin to overlap and become entangled, forming a cross-linked network or matrix.

In synovial joints, hyaluronan is produced by hyalocytes (mononuclear phagocytic cells) and released into the synovial fluid. Constant movement in the joint promotes the passage of hyaluronan into the acellular superficial layer of articular cartilage, where it is present in a concentration 5 times higher than in the deep layers of cartilage. Hyaluronan also penetrates into the extracellular matrix of the extracellular synovial tissue and capsule, filling the collagen matrix of the extracellular substance, where proteoglycans attach to it. The concentration of hyaluronan in normal synovial fluid is 2-4 mg/ml, which is 10 times higher than required for saturation. At such a high concentration, hyaluronan forms a continuous network of polysaccharide molecules surrounding collagen fibers. The primary function of haluronan in a healthy joint is to coat and protect the synovium and superficial collagen structure of cartilage from mechanical damage caused by friction due to flexion or body weight loading of the joint. The elastic-viscous nature of the network formed by hyaluronan allows it to adapt to applied mechanical load (both low-energy (flexion), where the hyaluronan molecules align in the direction of flow and behave like a viscous fluid, dissipating mechanical energy in the form of heat; and high-energy (impact) , exhibiting elastic properties, being absorbed to such a level that the energy is dissipated in a viscous flow.)

In addition to its rheological and mechanical functions, hyaluronan is able to physically inhibit the passage of large molecules such as fibrinogen into the joint space.

Currently, the pharmaceutical market offers more than twenty types of GLA preparations for intra-articular administration, differing in molecular weight (from 5 to 10,000 kDa), origin (natural, biosynthetic), molecular structure (linear or cross-linked), concentration (from 1 to 2%), the volume of the administered drug (from 1 to 3 ml), the number of injections per course (from one to five).

By origin they distinguish: 1) preparations obtained from cockscombs: Gialgan, Gialux, Atri Inzh, Rusvisk, Giruan Plus. 2) biosynthetic, obtained by bacterial fermentation: Ostenil, Fermatron, Sinokrom, Visco Plus, Suplazin. Preparations obtained from rooster combs can cause allergic reactions because they contain protein fragments and other pyrogens.

According to the structure of the molecule, hyaluronates are divided into: 1) native (from the word - nature-natural) long molecules obtained by bacterial synthesis: Fermatron, Ostenil, Sinokrom, Fermatron Plus, Suplasin. 2) so-called modified, cross-linked molecules: Duralan, Fermatron S, Synvisc. (Cross-linking of HA molecules is provided by two mechanisms: physical, due to electrostatic interaction, and chemical, due to the formation of covalent bonds. Since chemical stabilization is more resistant to temperature changes, it is preferable .

Hyaluronic acid preparations, which can be divided into 3 groups, depending on molecular weight. Molecular weight is one of the main characteristics that ensures the duration of the therapeutic effect of medications for intra-articular injections.

The rate of polymer degradation depends on the molecular weight. At low molecular weight, the polymer will quickly undergo separation until the molecular weight is reduced to critical values ​​and the drug is excreted from the body in the form of monomers and short linear polymers.

In the case of a high molecular weight, the degradation of the polymer will occur slowly, and accordingly the therapeutic effect will be prolonged.

The main preparations of HA depending on the molecular weight, structure of the molecules and accompanying additives.

Molecular weights are based on data published by the manufacturer or in the scientific press.

Low molecular weight HA drugs are quite well tolerated by patients when administered intra-articularly. Low molecular weight causes rapid breakdown of HA molecules in the joint and tissues. Literature data provide grounds for intentionally using low molecular weight HA preparations (500-750 kDa) of animal origin for extra-articular injections. We are talking about localizations where there is synovial tissue and HA is naturally produced to carry out metabolic processes, in particular the synovial sheaths and synovial membranes of tendons during chronic inflammation in this area (tendinitis, tenosynovitis, bursitis).

Medium molecular weight HA preparations represent the largest group. All of them are products of bacterial fermentation and in most cases are well tolerated by patients, but just like drugs with low molecular weight, they require 3 to 5 injections per course. A distinctive feature of some drugs from this group is the possibility of their use for injection into the joint cavity immediately after arthroscopic intervention for the speedy restoration of intra-articular metabolism.

HA preparations with active accompanying additives form a separate group, since along with the described properties they acquire new qualities.

A special group consists of GC preparations with the presence of cross-linked molecules. The presence of a significant number of intermolecular cross-links makes it possible to achieve a more pronounced analgesic effect by improving the shock-absorbing properties of the synovial fluid. Innovative technologies used in the production of this group of drugs have provided unique properties. The large number of cross-links and molecular structure allow for a single injection into the joint. The half-life can approach 4 weeks, which creates the preconditions for long-term catabolism. The transition from 3-5 injections to a single injection is a significant clinical benefit.

Let's consider the evidence for a broader role for NA in the treatment of OA beyond joint shock absorption and lubrication. Exogenous HA may reduce pain transmission and blunt the inflammatory cascade through the CD44 receptor, which is associated with OA, as well as stimulate the synthesis and deposition of extracellular matrix molecules, which are suppressed and degraded in the osteoarthritic joint. The effect of HA depends on the fragment size. In particular, long-chain high molecular weight HA is anti-inflammatory and can stimulate endogenous HA production, whereas shorter chain HA fragments are pro-inflammatory and can inhibit HA production at high concentrations.

The role of GC on disease progression.

Decreased HA synthesis, increased HA degradation, and increased oxidative stress lead to a decrease in both the concentration and average molecular weight of HA present in the synovium. Several studies have shown that exposure of chondrocytes and fibroblasts to HM HA fragments (<400 kDa) can cause increased activity of proinflammatory cytokines. In addition, it has been shown that the levels of IL-18 and IL-33 increase in mouse synovial fibroblasts after exposure to HA fragments, and that HA fragments enhance the inflammatory activity of macrophages. In contrast, high molecular weight hyaluronic acid has the opposite effect on some of these systems, inhibiting mediators such as TNF-α and IL-1β. HA receptor activity may be responsible for the long-lasting pain-relieving effect of intra-articular HA therapy, although the residence time of the exogenous molecule in the joint is quite short.

Hyaluronan products have certain rheological properties that inhibit nociceptors, acting as an elastic filter. There is also a reaction to chemical sensitization of nociceptors in inflamed joint tissues, possibly related to HA concentrations. Results from a study in cats with experimental arthritis showed that intra-articular injection of high molecular weight GC reduced the activity of nociceptive primary afferents at the onset and during movement, suggesting that joint lubrication is not solely responsible for the antinociceptive effects of NA.

Recently, single intra-articular injections of NA were shown to reduce pain by more than 50% compared with saline in the bradykinin/prostaglandin E2 (PGE2) model. Use of an anti-CD44 antibody abolished the inhibitory effects of NA on LPS-mediated increase in PGE2 production and COX-2 induction , indicating that the anti-inflammatory effect of GC was CD44 receptor mediated. Additional mechanisms that may contribute to the antinociceptive effects of GCs include inhibition of arachidonic acid release from fibroblasts and activation of opioid receptors. Exposure to GCs has been shown to reduce the secretion of arachidonic acid from fibroblasts taken from patients with knee OA and is stimulated by bradykinin. The results of one study showed that, in contrast to anti-inflammatory drugs, pain reduction resulting from GC administration was associated with stimulation of cartilage regeneration. The effects of NA and loxoprofen in the joint were experimentally compared. Both HA and loxoprofen significantly reduced pain in the rabbit OA model (partial menisectomy) and also reduced PGE2 production. Hyaluronic therapy also significantly inhibited cartilage degeneration, whereas loxoprofen did not.

Inflammatory effects.

High molecular weight HA may inhibit the inflammatory processes involved in OA by interfering with the effects of HM HA fragments on CD44, RHAMM, and TLR-2 and TLR-4. Results from in vitro and in vivo studies indicate that administration of high molecular weight GC has significant anti-inflammatory effects that are mediated, at least in part, by CD44 blockade. Administration of high molecular weight hyaluronic acid leads to suppression of IL-8 and NO synthase gene expression in cells that were not stimulated by IL-1. In cells that were stimulated with IL-1, TNF-α gene expression was also suppressed. Blocking CD44 with a specific antibody inhibited the effects of high molecular weight HA on proinflammatory gene expression. Recently, high molecular weight hyaluronic acid has also been shown to suppress IL-1β production in monocyte/macrophage cultures under various inflammatory conditions. Provision of IL-1β and TNF-α by GCs has important downstream effects on the expression of proinflammatory and catabolic molecules. IL-1β induces ADAMTS through p38 mitogen-activated protein kinase and NH2-terminal kinase phosphorylation in human fibroblast-like synovocytes. ADAMTS degrade aggrecan in cartilage; High molecular weight hyaluronic acid also suppresses ADAMTS expression. IL-1β suppresses peroxime proliferation-activating receptors. (PPARγ) . ( Peroxisome proliferator-activated receptors (PPARs), ligand-activated nuclear transcription factors (NTFs) from the hormonal receptor family, regulate the metabolism of fats and carbohydrates, cholesterol and bile acids, inflammation, regeneration and differentiation/proliferation of liver cells. All PPAR isoforms ( PARα, PPARβ/δ, PPARγ) are present in the liver, Activation of PPARs receptors most effectively reduces chronic inflammatory processes and has a lesser effect on acute inflammation. PPARα not only affects lipid metabolism and transport, FA oxidation and glucose homeostasis, but also exhibits anti-inflammatory effects effects. These effects are associated with inhibition of proinflammatory cytokines, adhesion molecules and extracellular matrix proteins or stimulation of the production of anti-inflammatory molecules. In general, PPARα reduces the production of proinflammatory cytokines, which limits inflammatory reactions and atherogenesis). PPAR activity is regulated by products of lipid metabolism and other natural and synthetic activators and increases the expression of MMPs. Results from a study examining the expression of inflammatory genes in human chondrosarcoma cells induced by IL-1β show that high molecular weight hyaluronic acid increases the expression of PPARγ and decreases that of COX-2, MMP-1 and MMP-13. Additional anti-inflammatory effects of GC are achieved through the suppression of mitogen-activated protein kinases and nuclear factor signaling. In a rabbit model that induced OA through injection of sterile papain into the knee, intra-articular injection of HA resulted in a significant decrease in IL-1β and TNF-α expression and an increase in TIMP-1 expression compared with intra-articular saline controls. GC treatment also resulted in chondrocyte proliferation in this model. Exogenous HA also reduces levels of inflammatory cytokines and MMPs in tissues collected from patients with OA and other conditions associated with joint damage. In one study, subacromial synovial fibroblasts were taken from patients with rotator cuff disease and stimulated with IL-1β. The addition of GC resulted in a dose-dependent decrease in the expression of IL-1β, TNF-α and IL-6. These effects of GC were lost when CD44 was blocked by anti-CD44 antibody. Incubation with GC has also been shown to inhibit IL-1β-induced MMP activity in synovial tissue from patients.

Changes in the extracellular matrix alter the biomechanical environment of chondrocytes and lead to disease progression. The ECM is integrally involved in the development and progression of OA, and its preservation and restoration have become the focus of treatment. The results of several studies have shown that exogenous NA can increase the synthesis of ESM molecules. Exogenous HA stimulates synovial fibroblasts to produce new HA. When synovial fibroblasts from the knees of osteoarthritis rabbits were cultured with HA formulations of varying molecular weights, the amount of newly synthesized HA depended on both the concentration and molecular weight of exogenous HA. Higher molecular weight agents stimulated GA synthesis more strongly, while low molecular weight GAs suppressed GA synthesis when used in high concentrations. Two additional studies showed that intra-articular injection of HA in patients with OA increased endogenous NA production. In in vitro experiments, treatment of bovine articular chondrocytes with HA caused a significant increase in the synthesis of sulfated glycosaminoglycan and hydroxyproline, which coincided with an increase in matrix deposition of chondroitin-6-sulfate and type II collagen. Mechanical stress leading to injury has been shown to result in the loss of proteoglycans from cartilage and may play a role in the development and progression of OA, whereas administration of HA has been shown to increase proteoglycan synthesis in cartilage exposed to mechanical stress. In 2007, a review of disease-modifying drugs for OA devoted only one paragraph to HA, stating that there was no evidence that HA provided a disease-modifying effect. This conclusion was based on the observation that intra-articular injection of HA into the knee had no significant effect on radiographic progression versus intra-articular saline over 1 year of follow-up.

A 2006 Cochrane review of randomized trials concluded that viscofilling with HA (or hylan derivatives) was superior to placebo in improving pain and function over several weeks. In addition, viscosupplementation has generally demonstrated benefits over a longer period of time compared with intra-articular corticosteroid injections. Systematic reviews have also shown the safety and effectiveness of GC over non-steroidal anti-inflammatory drugs and other non-surgical treatments. It is becoming increasingly clear that NA influences a wide range of biological processes through multiple molecular pathways.

In October 2021, J Arthroplasty published one interesting study that compared injections of low-, moderate-, and high-molecular-weight hyaluronic acid during surgical delay. The study included 30,417 patients. The effectiveness of low molecular weight (MW) hyaluronic acid injections, moderate molecular weight HA (MMWHA) injections, and high molecular weight HA (HMWHA) injections for preventing or delaying knee surgery in patients with knee osteoarthritis was compared. According to the study results, there was no significant difference in the likelihood of surgery between LMWHA, MMWHA, and HMWHA users after controlling for empirically based factors.

Another study (double-blind, randomized, multicenter) (BMC Musculoskelet Disord, 2021 May 26) tested the efficacy and safety of a single injection of cross-linked sodium hyaluronate versus three injections of high molecular weight sodium hyaluronate for knee osteoarthritis.

Two hundred eighty-seven patients with osteoarthritis (Kellgren-Lawrence grades I-III) were randomized to each group. Three weeks of injections were given in both groups, but two physiological injections were preceded by cross-linked hyulronate injections to maintain double blindness. The primary endpoint was change in severe weight-bearing pain (WBP) 12 weeks after the last injection. Secondary endpoints included the Western Ontario and McMaster Osteoarthritis Index; global patient and investigator assessment; pain at rest, at night or with movement. This study showed that a single injection of cross-linked hyaluronan was as effective as three injections of high molecular weight sodium hyaluronate in reducing WBP.

In a review and analysis of 68 studies, products with an average molecular weight ≥3000 kDa provided favorable efficacy results compared with products with an average molecular weight <3000 kDa. Products with molecular weights ≥3000 kDa demonstrated significantly lower rates of discontinuation due to treatment-related side effects than their counterparts ≤1500 kDa. In addition, biological fermentation HA had a significantly lower incidence of effusion than HA obtained from poultry. Biological fermentation HA demonstrated fewer inflammatory responses at the injection site than avian-derived HA products. In the available literature, IA-GCs products with molecular weight ≥ 3000 kDa and those derived from biological fermentation show excellent clinical observations and minimal side effects.

Another interesting study was published in the journal Int J Mol Sci 2021 Mar 17, which compared the effectiveness and cost of treatment with stabilized hyaluronic acid (Durolane) in one injection with standard hyaluronic acid (HA) preparations in five injections for osteoarthritis (OA) of the knee. Patients were randomized into two groups: group I with intra-articular injection of NANA (Durolane®) and group II with HA (Go-ON®). Control examinations of patients were at the 1st, 2nd, 4th, 8th, 12th and 26th week after treatment. A statistically significant improvement in WOMAC score was observed in patients receiving NAHA compared to those receiving GC at week 26. In addition, the need for analgesia was significantly reduced at week 26 in the NANA-treated group. Finally, economic analysis showed an increased cost of overall treatment with HA injections. Our data supports the use of the ANAS class of products for the treatment of the knee joint

A systematic review and meta-analysis of electronic database data, including PubMed and Embase, conducted from January 1980 to November 2015 evaluated the effectiveness of 3 injections of sodium hyaluronate (Hyalgan) compared with 5 injections into the knee joint. The review included studies that assessed the effectiveness of a course of 3 or 5 weeks of intra-articular injections of Hyalgan for the treatment of OA knee pain. Clinical studies evaluating the effectiveness of a 3-week course of other US-approved hyaluronic acid products were also included. 24 studies were identified, including 2168 study participants in 30 cohorts processed. Meta-analysis results indicated that knee pain relief with a 3-week course of Gialgan was similar to a 5-week course of Gialgan (P = 0.916). The level of pain reduction from baseline pain with a 3-week course of Hyalgan is similar to a 3-week course of other HA products. There was no statistical difference between the reduction in knee pain with a 3-week course of Hyalgan compared to the reduction in OA knee pain with a 5-week course of Hyalgan or a three-week course of other HA products.

Groups of scientists conducted a meta-analysis of 20 studies with 3034 patients that compared the effectiveness of Synvisc with low molecular weight hyaluronic acids. According to the results, limited data showed a superior effect for hylan GF 20 compared to low molecular weight hyaluronic acid at 2 to 3 months after injection (assessed by VAS and WOMAC scores). There was no evidence of an increased risk of treatment-related side effects for hylan GF 20 injections.

Hylan GF 20 is a product of animal origin and consists of two fractions. Their molecular weight is 6 million Da, which is very close to healthy synovial fluid. This makes it possible to restore the viscoelastic properties of the synovial fluid to a greater extent and improve the functional state of the joint. The clinical effect of the drug has been demonstrated in numerous clinical studies: the analgesic effect of hylan GF 20 was longer lasting compared to standard NSAID therapy. - persisted in 28% of patients versus 6% of patients who took only NSAIDs and compared with intra-articular corticosteroids. — 56% of patients versus 37% of patients; this effect lasted significantly longer and also made it possible to delay endoprosthetics of the affected joint by 3.8 years. The use of hylan GF 20 for the treatment of OA has allowed patients to reduce the need for other medications. The design of the studies conducted with hylan GF 20 underscores their high degree of reliability. The clinical effectiveness of the drug is confirmed by the dynamics of laboratory parameters both in vitro and in vivo. In vitro, in a rabbit model of osteoarthritis, not only the chondroprotective effect of hylan GF 20 was shown, but also a decrease in the formation of osteophytes. It has also been found that hylan GF 20 can stimulate cartilage repair by increasing Col II and inhibits IL-1p-mediated cartilage matrix degradation by decreasing metalloproteinase activity. The chondroprotective effect of hylan GF 20 was also confirmed by the dynamics of serum levels of Coll2-1 and Coll2-1 NO2, which are biomarkers of OA. Three intra-articular injections of 2 ml of Synvisc led to a statistically significant decrease in their levels, while their dynamics were more pronounced in patients with stages III-IV of OA according to Kellgren.

Side effects with intra-articular administration of GC drugs rarely develop - on average in 1-13% of patients and are, as a rule, local in nature. Most often, pain occurs at the injection site. Any intra-articular injections may be accompanied by an inflammatory response, but the literature describes cases of the development of a clinically isolated reaction, known as a spontaneous acute inflammatory reaction (SAIR), during intra-articular administration of GC drugs to patients with OA. It is not yet clear, however, whether these pseudoseptic reactions are directly related to GC.

The technique of intra-articular administration of the drug is important: when using an anterior approach to the knee joint, the frequency of side effects is usually higher than when introducing GC into the joint through a lateral approach. This can be explained by the fact that in the first case the drug is sometimes administered not into the joint cavity, but paraarticularly.

The analysis of the literature on the role and properties of HA, the use of synovial fluid replacement agents based on it, indicates the high significance of this segment of therapy in the relief of articular and periarticular pain syndrome, and high efficiency in the complex treatment of OA. Drugs with high molecular weight demonstrate the longest analgesic effect up to 8-12 months and a more pronounced improvement in functional activity. Recent data and observations have made it possible to better understand the mechanisms of GC metabolism and determine the features of the use of GC preparations depending on the characteristics of production, molecular weight and other pharmacological and pharmacodynamic properties.

Adverse reactions

The physician should monitor patients who have ever had an allergy to any other drugs and patients with liver disease. If the dosage is incorrect or an allergic reaction, side effects are possible:

• redness and swelling in the area where the drug was administered;
• dizziness;
• nausea;
• temperature increase;
• disturbance of appetite and sleep;
• general weakness.

These symptoms do not require additional treatment; the patient’s condition returns to normal within a few hours after the injection. In some cases, the doctor may recommend interrupting the course.

After the injection, the joint area may become swollen and red, but these phenomena will go away on their own in the coming days.

special instructions

• The drug is intended for use as an intra-articular implant. It is prohibited to re-sterilize the fluid or mix it with other products.
• Do not inject this drug into blood vessels or surrounding tissue.
• The physician should monitor patients who have ever had an allergy to any other drugs and patients with liver disease.
• Do not use the product contained in damaged packaging.
• The syringe, needle and any other unused materials should be disposed of immediately after the treatment session. Repeated use of the same syringe may cause patient death due to infection or inflammation.
• The drug can only be prescribed by healthcare professionals certified in accordance with current national legislation.

Before using this product, be sure to read the instructions.

Use during pregnancy and lactation

The use of the drug can be prescribed if the expected benefits of treatment outweigh the harm from possible side effects. Nursing mothers should stop breastfeeding their baby during treatment.

Use in childhood

The safety of the product for the treatment of children has not been verified, so the doctor must exercise special supervision of the patient during therapy.

Use in old age

Since organ functions in older people are often weakened, the doctor must exercise special supervision over them during therapy.

Older people need to be monitored after a joint injection

Components of Sustafast and what is its magic

Following Sustafast's annotation, it is important to consider the production of the drug in order to understand whether it is really able to cope with the promised result.
The composition of the product is natural, it is created for the active regeneration of damaged tissues. The drug includes:

• Chondroitin;
• Shark liver;
• Glucosamine;
• Sabelnik extract;
• Clover extract.

Chondroitin actively regenerates cartilage, tendons and ligaments, strengthens them, while simultaneously relieving inflammation and swelling. Due to the shark liver, the product fights infections, improves blood flow and increases joint mobility. In addition, the cream copes with stagnant formations thanks to this component.

Glucosamine prevents any destruction of joints and ligaments, consolidates the result of treatment, and how long the treatment will last depends on it. Purchasing Sustafast for joints also makes sense because it contains extracts of cinquefoil and clover, which:

• stop bleeding;
• promote the formation of a protective film;
• nourish connective tissue.

An important factor is the safety of using the gel, because its composition is completely natural and it does not carry with it any side effects. Thus, the remedy is an excellent medicine for any problems that limit physical activity. The main thing is to use it responsibly, do not skip times of use and do everything in accordance with the manufacturer’s recommendations.

Initially, the medication is distributed between the palms, then with active movements it is necessary to rub it into the problem area, evenly distributing it over it and the nearest areas of the skin. Continue doing this until the gel is completely absorbed. A big plus is that Sustafast is sold in ampoules - they are convenient and easy to use and help you understand how much of the drug will be needed per use.

Analogues of the drug Versan Fluid

If you couldn’t buy Versan Fluid or the price seems too high, you can use other preparations based on hyaluronic acid. One of the most affordable options is Suplazin. The injection solution, placed in sterile disposable syringes, acts quickly and effectively, rarely causing side effects. The cost of 1 syringe of Suplazin is almost 2 times lower.

Other analogues of Versan can be used to treat osteoarthritis:

• Ostenil Mini;
• Duralan;
• East Tendon;
• Ostenil;
• Fermathron S;
• ViscoPlus;
• Hymovis;
• Hyalur;
• Giastat;
• Hyaluform;
• Hyalubrix;
• Intraject;
• Sinokrom Forte;
• Viscosil.

Before choosing one option or another, you should consult your doctor. All drugs offered are sold by prescription only; injections must be administered by a medical professional. Self-medication can do more harm than good.

Reviews from patients and doctors

Reviews from patients about the drug are contradictory . Among the advantages is its effectiveness in exacerbations of osteoarthritis. Patients experience relief after the first injection; completing the full course guarantees a decrease in pain and swelling. The appearance of the affected limb also improves.

The high price causes complaints. For 1 syringe you will have to pay more than 6,000 rubles, and a standard three-week course will require 3 packages of medicine. When administering the drug:

• severe pain may be felt;
• temporary numbness of the limb;
• edema;
• temperature increase.

Some patients, after 1 injection, refuse to continue the course, preferring to be treated with tablets, capsules, ointments and gels.

Doctors prescribing the drug note that the injections are safe, and severe or systemic side effects are extremely rare. With the classical treatment regimen, the patient also does not face complications. The pain goes away after a few hours, and the effectiveness of the treatment significantly outweighs the possible inconvenience. However, older patients may tolerate injections less well, so patients over 65 years of age are prescribed the medicine with caution.