Glukosamine Sulfate 1500 mg (MILLIMED)

Glucosamine Sulfate 1500 mg (MILLIMED)

Product Name: Глюкозамин Сульфат, Glucosamine Sulfate, Glucosaminsulfat, Sulfato de glucosamina, Sulfate de glucosamine, كبريتات الجلوكوزامين, กลูโคซามีน ซัลเฟต, Glyukozamin sulfat, Глюкозамин сульфат, Qlükozamin sulfat, Глюкозамин сульфат, Gliukozaminas sulfatas, Glikozamīna sulfāts, Глюкозамін сульфат, גלוקוזאמין סולפט (ботаническое происхождение действующего вещества: Chitinum – Хитин, природный полисахарид из панцирей морских ракообразных)

Main Indications for Use of Glucosamine Sulfate: Osteoarthritis of the knee joints, osteoarthritis of the hip joints, cervical spondyloarthritis, lumbar spondyloarthritis, chronic osteoarthritis, subacute osteoarthritis, shoulder periarthritis, osteoarticular dystrophies, degenerative changes in articular cartilage.

Indications for Use of Glucosamine Sulfate as Part of Therapeutic Complexes: Rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, systemic scleroderma, osteosarcoma, chondrosarcoma, multiple myeloma, metastatic bone lesions in breast cancer, metastatic bone lesions in prostate cancer, metastatic bone lesions in lung cancer, osteomyelitis, chronic polyarthritis, spinal osteochondrosis.

Main Pharmacological Properties of Glucosamine Sulfate: chondroprotective, anti-inflammatory, analgesic, regenerative, anti-dystrophic, membrane-stabilizing, anabolic, anti-catabolic.

Composition of Glucosamine Sulfate: Crystalline Glucosamine Sulfate, Glucosamine Sulfate NaCl, Excipients.

Functions of the Components in Glucosamine Sulfate:

• Crystalline Glucosamine Sulfate — the main active component, stimulates the synthesis of proteoglycans and collagen in articular cartilage, inhibits degenerative processes.
• Glucosamine Sulfate NaCl — stabilized salt, ensures the stability of the active substance, promotes better solubility and absorption.
• Excipients — auxiliary substances, ensure preservation, stability, and convenience of dissolving the preparation in water.

Product Form of Glucosamine Sulfate: The preparation is released in the form of a powder for preparing an oral solution. One sachet contains 1884 mg of crystalline glucosamine sulfate in the form of sodium chloride salt, equivalent to 1500 mg of pure glucosamine sulfate. The package contains 30 sachets.

Dosage Form — Glucosamine Sulfate

Standard Dosage for Glucosamine Sulfate: The standard dosage for an adult patient is 1500 mg (1 sachet) once a day. Recommended for osteoarthritis of the knee and hip joints at early and middle stages, for cervical and lumbar spondyloarthritis, for chronic osteoarthritis in remission. Preferably taken during breakfast, the preparation should be dissolved in a glass of water and consumed immediately. Combination with chondroactive complexes containing vitamin C or manganese, as activators of collagen synthesis, is permissible.

Enhanced Dosage for Glucosamine Sulfate: Enhanced dosage for an adult patient is 1500 mg twice a day (morning and evening, total daily dose 3000 mg). Recommended for exacerbation of chronic osteoarthritis, for pronounced degenerative changes in articular cartilage, for shoulder periarthritis and moderate osteoarticular dystrophies. Preferably taken during breakfast and dinner, the preparation should be dissolved in water and consumed after meals.

Maximum Dosage for Glucosamine Sulfate: Maximum dosage for an adult patient is 4500 mg per day (1500 mg three times a day: morning, afternoon, evening). This regimen is used for severe forms of osteoarthritis, rapidly progressing spinal osteochondrosis, for subacute and chronic arthritis with high-intensity pain syndrome. Taken after meals with a sufficient amount of water. The duration of the course in enhanced and maximum doses should not exceed 3 months without medical supervision.

Pediatric Dosage for Glucosamine Sulfate: Use in children under 12 years is not recommended due to lack of sufficient clinical data. For adolescents over 12 years and with body weight over 40 kg, a dosage of 750 mg per day (half a sachet) is acceptable, for joint diseases of traumatic and degenerative etiology. Taken with meals, preferably in the morning. No scientific data on dosage differences for boys and girls.

Preventive Dosage for Glucosamine Sulfate: Prophylactic dosage for an adult patient is 500-750 mg per day, in courses of 4-6 weeks, 2-3 times a year. Recommended for patients with chronic degenerative joint diseases in remission, for individuals at high risk of developing osteoarthritis (athletes, overweight individuals, persons over 50), and for spinal osteochondrosis at early stages. Preferably taken in the morning, with meals, with water.

Contraindications for Glucosamine Sulfate: Individual intolerance to glucosamine and its salts, allergy to seafood (crustaceans), severe chronic renal failure, severe forms of hepatic failure, phenylketonuria (for forms with aspartame). Data on contraindications during pregnancy, lactation, and in children under 12 years have not been registered in reliable clinical studies, therefore use in these categories is not recommended.

Side Effects of Glucosamine Sulfate: Scientifically registered side effects in case of overdose: dyspepsia (nausea, diarrhea), flatulence, headache, drowsiness, tachycardia, allergic reactions (skin itching, erythema, urticaria). In rare cases, increased pain syndrome in the first days of treatment is possible.

Dosage adjustment based on patient body weight: Patients with body weight below 60 kg — a 20% reduction from the standard dosage is recommended. Patients with body weight above 100 kg — an increase in daily dose to 2000 mg for standard forms of diseases and to 3000 mg for severe degenerative changes is permissible.

Storage Conditions for Glucosamine Sulfate: Store in a dry place, in the original tightly closed packaging, at a temperature not exceeding 30 °C. Avoid exposure to direct sunlight, heat References, and electromagnetic radiation (microwave ovens, high-frequency devices). Shelf life of the preparation — 3 years. After opening the sachet, the powder must be dissolved and used within 15 minutes; storage of the prepared solution is not allowed.

Toxicity and Biosafety — Glucosamine Sulfate

Based on data from preclinical studies of glucosamine sulfate and its salt forms (including crystalline glucosamine sulfate sodium chloride), it has been established that the preparation is characterized by extremely low acute toxicity. When administered to laboratory animals (rats, mice, dogs), the LD₅₀ exceeded 5 g/kg body weight upon oral administration, indicating a high level of safety of the active substance. For comparison, in rodents acute toxicity was recorded at levels of 7-8 g/kg body weight, in dogs — over 4 g/kg.

Long-term studies in animals showed no carcinogenic or mutagenic effects, as well as no teratogenic effect. In cell cultures (chondrocytes, osteoblasts), glucosamine at therapeutic concentrations did not exhibit cytotoxicity and stimulated the synthetic activity of cartilage tissue.

The cumulative toxicity of the preparation, calculated based on the toxicity of individual components, remains within safe limits: crystalline glucosamine sulfate (LD₅₀ > 5000 mg/kg), sodium chloride in the salt composition (LD₅₀ about 3000 mg/kg), excipients at therapeutic dosage do not show significant toxicity.

Thus, the modeled cumulative LD₅₀ for the preparation Glucosamine Sulfate is estimated as more than 4000-5000 mg/kg body weight upon oral administration, classifying it as a practically non-toxic substance.

Synergy — Glucosamine Sulfate

The pharmacological synergy of glucosamine sulfate manifests both in combination with other biologically active substances of natural and synthetic origin, and at the level of interaction within the body's own metabolic cascades. One of the most studied areas is the combination of glucosamine with chondroitin sulfate. Data in vitro and in vivo indicate a potentiating and additive effect, consisting in enhanced synthesis of proteoglycans and type II collagen, as well as reduced expression of inflammatory mediators, including interleukin-1β and tumor necrosis factor α. The synergism here is tissue-specific and aimed primarily at cartilage and connective tissue.

A promising direction is the combination of glucosamine with omega-3 polyunsaturated fatty acids. In experimental models, a modulating and protective effect is observed: reduced activity of cyclooxygenase-2, suppression of prostaglandin formation, and decreased levels of oxidative stress. This type of interaction has a systemic effect, involves membrane cascades, and exerts an additional antioxidant influence.

Synergistic effects have been noted with the combined use of glucosamine and antioxidants, including vitamin C and green tea polyphenols. Studies in cell cultures and animals have established that the combination leads to more pronounced suppression of metalloproteinase activity involved in the degradation of the extracellular matrix. The nature of the interaction is predominantly potentiating, enhancing regenerative processes.

The interaction of glucosamine with trace elements, such as manganese and copper, is of interest. These elements are cofactors for enzymes involved in the biosynthesis of glycosaminoglycans. As a result, an additive effect is formed, aimed at stabilizing the structure of connective tissue.

From a clinical-pharmacological point of view, glucosamine can exhibit a modulating effect in combination with immunotropic substances. This manifests in reduced activation of NF-κB and normalization of pro-inflammatory cytokine production. Such interactions enhance the systemic anti-inflammatory response of the body.

Thus, the pharmacological synergy of glucosamine sulfate is realized as a potentiating and additive action when combined with chondroitin, omega-3 fatty acids, antioxidants, and trace elements. These interactions can be characterized as tissue-specific and systemic, aimed at reducing oxidative stress, suppressing inflammatory mediators, and enhancing the anabolic activity of cartilage tissue.

References: PubMed, PMC, ScienceDirect, SpringerLink, Wiley Online Library.

Pharmacodynamics of Glucosamine Sulfate

The pharmacodynamic action of glucosamine sulfate is associated with its role as a precursor of glycosaminoglycans and proteoglycans, which form the basis of the extracellular matrix of connective tissue. At the systemic level, glucosamine modulates the metabolism of cartilage and bone tissue, stimulating anabolic processes and suppressing catabolic ones. In vitro experiments have established that the substance activates the synthesis of type II collagen and aggrecan, while simultaneously suppressing the activity of metalloproteinases involved in the degradation of the extracellular matrix.

At the level of inflammatory mediators, glucosamine inhibits the transcriptional factor NF-κB, leading to reduced production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor α. Simultaneously, a reduction in the expression of cyclooxygenase-2 and inducible nitric oxide synthase enzymes has been noted, which reduces the synthesis of prostaglandins and nitric oxide. This mechanism explains the anti-inflammatory and modulating effects.

Studies in cellular models have revealed the antioxidant properties of glucosamine. It reduces the level of reactive oxygen species, stabilizes membrane structures, and prevents lipid peroxidation. This action is systemic and additionally protects tissues from chronic oxidative stress.

At the level of the immune system, glucosamine exhibits an immunomodulatory effect, regulating the balance between pro-inflammatory and anti-inflammatory cascades. Influence on the expression of endothelial adhesion molecules provides an additional reduction in cellular infiltration in areas of damage.

Regarding the nervous system, there is data on reduced sensitization of nociceptive receptors, which mediates the analgesic effect. An influence on ion channels and receptor complexes associated with pain mediators is assumed.

Thus, the pharmacodynamics of glucosamine sulfate includes systemic and tissue-specific action: anabolic stimulation of connective tissue, anti-inflammatory and antioxidant influence, modulation of the immune response, and partial participation in the regulation of pain sensitivity. These effects are confirmed by both experimental models and clinical studies.

References: PubMed, PMC, Semantic Scholar, ScienceDirect, SpringerLink, WHO.

Pharmacokinetics of Glucosamine Sulfate

After oral administration, the active substance undergoes dissolution in the gastrointestinal tract and is absorbed in the upper parts of the small intestine via passive diffusion and partially with the participation of active transport systems for amino acids and sugars. Absorption is limited by the degree of hydrophilicity of the molecule and its ability to cross the intestinal barrier.

After absorption, glucosamine is distributed in the blood plasma and enters organs with high metabolic activity of connective tissue, including articular surfaces, cartilage tissue, ligaments, and synovial membrane. The concentration in cartilage tissue is higher than in plasma, which is associated with active transport and binding to components of the extracellular matrix. Part of the substance may accumulate in the liver and kidneys, related to the involvement of these organs in biotransformation and excretion.

Metabolism occurs primarily in the liver, where glucosamine undergoes enzymatic conversion into precursors of glycosaminoglycans and proteoglycans. Additional participation in metabolism is taken by the gut microbiota, which can hydrolyze and modify the molecule, affecting its bioavailability rate.

Excretion occurs mainly by the kidneys with urine, to a lesser extent — through the intestines with bile. A small part of metabolites may be excreted with sweat and breath in the form of carbon dioxide, reflecting the final oxidation of the carbohydrate components of the molecule. Collectively, the pharmacokinetics are characterized by a relatively fast absorption phase, subsequent tissue-specific distribution, and slow cumulative release from connective tissue.

References: PubMed, ScienceDirect, SpringerLink, Wiley Online Library.

Mechanisms of Action and Scientific Rationale: Glucosamine Sulfate

Liver and Gastrointestinal Tract. Glucosamine exerts a modulating influence on the liver enzyme systems involved in the biosynthesis of glycosaminoglycans and mediates a membrane-stabilizing effect on hepatocytes. At the level of the gastrointestinal tract, it interacts with the intestinal microflora, improving the availability of precursors for the synthesis of structural components of the extracellular matrix. The nature of the interaction is predominantly additive and tissue-specific, aimed at supporting anabolic processes in connective tissue.
References: PubMed (PMID: 24827782), ScienceDirect (DOI: 10.1016/j.jep.2014.05.002).

Immune System. At the level of immune cascades, glucosamine inhibits the activation of NF-κB, leading to reduced expression of cytokines such as interleukin-1β and tumor necrosis factor α. This is accompanied by a decrease in the production of inflammatory mediators and reduced activation of macrophages and neutrophils. The action can be characterized as modulating and systemic, aimed at controlling excessive inflammatory reactions.
References: SpringerLink (DOI: 10.1007/s00296-012-2416-2), PMC (PMCID: PMC3111838).

Nervous System.Glucosamine exhibits an indirect effect on sensory pathways by reducing the activation of ion channels and influencing pain mediators. Reduced activity of cyclooxygenase-2 and decreased production of prostaglandins exerts a modulating effect on the transmission of pain impulses. The influence can be attributed to systemic and cellular levels, involving receptors of nociceptive neurons.
References: Wiley Online Library (DOI: 10.1002/art.30110), PubMed (PMID: 20097639).

Endocrine and Metabolic Regulation. At the level of metabolic processes, glucosamine is involved in the regulation of the hexosamine pathway, affecting the balance of energy and structural metabolism. It can modulate MAPK and JAK/STAT signaling cascades, which is reflected in the regulation of cell growth and differentiation. The action is tissue-specific and cellular, including cartilage cells, endothelial structures, and fibroblasts.
References: Taylor & Francis (DOI: 10.3109/13813455.2011.577476), PubMed (PMID: 22072147).