Jointsyno V

Uses

Hyaluronic acid is a glycosaminoglycan used for the relief of joint pain, wound healing, ophthalmologic treatment, cosmetic treatment, and various other applications.

The intra-articular preparations of hyaluronic acid are indicated for knee pain associated with osteoarthritis. Hyaluronic acid is used in cosmetic applications to prevent and reduce the appearance of wrinkles on the face, and as a dermal filler to correct facial imperfections or other imperfections on other parts of the body. It is frequently an ingredient in topical applications for wound healing and symptomatic treatment of skin irritation from various causes. Hyaluronic acid may also be indicated in ophthalmological preparations or oral capsules to treat discomfort caused by dry eyes or conjunctivitis and for its protective qualities during and before eye surgery. Finally, hyaluronic acid can be used off-label to coat the bladder for relief of interstitial cystitis symptoms.

Magnesium is a medication used for many purposes including constipation, indigestion, magnesium deficiency, and pre-eclampsia.

Healthy levels of magnesium can be achieved through a well balanced diet, but if food sources are insufficient, magnesium supplements can be used to prevent and treat magnesium deficiencies.

In medicine, various magnesium salts may be used in laxative and antacid products. For example, magnesium citrate is available over-the-counter and may be used to manage occasional constipation. Magnesium sulfate may be used on its own or with total parenteral nutrition to treat hypomagnesemia. Magnesium sulfate is also indicated to prevent seizures in pregnant women with pre-eclampsia, and to manage seizures associated with eclampsia.

Jointsyno V is also used to associated treatment for these conditions: Actinic Keratosis (AK), Burns, Chronic Skin Ulcers, Conjunctivitis, Dehydration, Dermabrasion, Dermatosis, Dry Eyes, Facial Defect, Interstitial Cystitis, Keratoconjunctivitis, Ocular Irritation, Osteoarthritis (OA), Pain of the knee, Seasonal Allergic Conjunctivitis, Skin Burn, Skin Irritation, Skin fissures, Tissue Adhesions, Varicose Ulcers, Wounds, Eye discomfort, Facial fine wrinkling, Sensation of burning in the eyes, Superficial Wounds, Dermal Filler, Synovial Fluid Lubrication, Wound HealingCalcium Deficiency, Magnesium Deficiency, Zinc Deficiency

How Jointsyno V works

General principles and hyaluronic acid receptor binding

Hyaluronic acid works by two basic mechanisms: serving as a passive structural molecule or serving as signaling molecule, depending on the molecule size. The physicochemical properties of high molecular weight HA contribute to passive structural effects, demonstrating hygroscopicity and viscoelasticity and improving hydration, water balance, and structural integrity. As a signalling molecule interacting with proteins, HA causes several opposing effects based on molecular weight: pro- or anti-inflammatory effects, promotion or inhibition of cell migration, and activating or inhibiting cell division.

Hyaluronic acid exerts its therapeutic effects through binding to three primary types of cell surface receptors: CD44 (a membrane glycoprotein), the receptor for hyaluronate-mediated motility (RHAMM), and the Intercellular Adhesion Molecule 1 (ICAM-1). CD44 is considered the most widely distributed receptor for hyaluronic acid, demonstrating cellular interactions with osteopontin, collagen, and matrix metalloproteinases (MMPs). High and low molecular weight hyaluronic acids demonstrate differing molecular and cellular mechanisms in their interaction with CD44 receptors. Some examples of these effects include modification of chondrocyte survival pathways in addition to alteration of apoptosis pathways. Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), and hyaluronic acid receptor for endocytosis (HARE), (also known as Stabilin-2) also bind to hyaluronic acid.

Hyaluronic acid for skin conditions and cosmetics

Hyaluronic acid's anionic proprieties cause it to attract water and induce swelling, increasing tissue volume and skin structural integrity. The aging process is associated with reduced production of skin hyaluronic acid and collagen, causing the appearance of wrinkles and the loss of facial volume. Dermal fillers of hyaluronic acid replace lost tissue volume, imparting a full and youthful appearance to skin that has lost its elasticity. Hyaluronic acid fillers contain cross-linked hyaluronic acid particles, rendering a concentrated substance with resistance to various forms of physical and chemical breakdown. The cosmetic benefits of hyaluronic acid filler may last up to 6 months, depending on the brand and technique used for injection. Additionally, dermal hyaluronic acid fillers are known to increase the production of fibroblasts, supporting wound healing and offering relief from irritating and inflammatory skin conditions.

Hyaluronic acid for joint pain

Most cells in the human body are capable of synthesizing HA. It is a primary component of the extracellular matrix (ECM) and can be found in bone marrow, cartilage, and synovial fluid in joints. In osteoarthritis, the concentration of naturally occurring hyaluronic acid gradually decreases, lowering the viscosity of synovial fluid that protects joints from excess friction. Administration of intra-articular hyaluronic acid increases viscosity of synovial joint fluid, reducing friction and subsequently relieving painful arthritic symptoms.

Hyaluronic acid for ophthalmic conditions and ophthalmological procedures

Solutions of hyaluronic acid with a concentration greater than 0.1% moisturize the surface of the eyes to treat symptoms of dry eye while improving the stabilization of tear film, replenishing deficiencies of HA, reducing friction, and preventing binding of foreign substances to the ocular tissue. Hyaluronic acid is frequently used during and after ophthalmological surgeries and plays important roles by virtue of its moisturizing, viscoelastic, and protective properties. It promotes tissue healing of the corneal epithelium and other parts of the eye following ophthalmological surgery, minimizing the risk of adhesions and free radical formation.

Magnesium is a cofactor for at least 300 enzymes and is important for several functions in the body with some key processes identified below. Enzymes that rely on magnesium to operate help produce energy through oxidative phosphorylation, glycolysis and ATP metabolism. They are also involved in nerve function, muscle contraction, blood glucose control, hormone receptor binding, protein synthesis, cardiac excitability, blood pressure control, gating of calcium channels and transmembrane ion flux.

The mitochondrial intracellular space is rich in magnesium, since it is required to produce the active form of ATP (adenosine triphosphate) from ADP (adenosine diphosphate) and inorganic phosphate, and behaves as a counter ion for the energy rich molecule. Additionally, magnesium is essential for ATP metabolism.

Toxicity

The oral LD50 of the sodium salt of hyaluronic acid is >800 mg/kg in the rat. Overdose information is not readily available in the literature. The safety profile for hyaluronic acid favourable, however, single case reports of death following vaginal injection of hyaluronic acid are published; the deaths likely occurred due to poor procedure regulation.

The recommended dietary allowance of magnesium ranges from 30 mg for infants to 420 mg for males between the age of 31 and 50. According to the institute of Medicine (IOM), the majority of adults can tolerate 350 mg of magnesium per day without experiencing adverse effects. Symptoms of magnesium toxicity include diarrhea and other gastrointestinal effects, thirst, muscle weakness, drowsiness, severe back and pelvic pain, hypotension, dizziness, confusion, difficulty breathing, lethargy, and deterioration of kidney function. Other more severe symptoms associated with magnesium overdose include loss of consciousness, respiratory arrest, cardiac arrhythmias and cardiac arrest.

Regular use of laxatives containing magnesium may lead to severe and even fatal hypermagnesemia.

Discontinuation of magnesium products including supplements, laxatives, and antacids is usually sufficient to manage mild cases of magnesium overdose; however, patients should also be screened for renal impairment.

In severe cases of magnesium overdose, patients may require supportive care and interventions including intravenous fluids and furosemide, IV calcium chloride or calcium gluconate, renal dialysis and artificial respiratory support.

Volume of Distribution

There is limited information in the literature regarding the human pharmacokinetics of hyaluronic acid. After a dermal filler injection, HA distributes rapidly into the superficial and deep dermis. Hyaluronic acid is distributed to skin of rats after intestinal metabolism into oligosaccharides. In rats and beagle dogs receiving oral hyaluronic acid, HA accumulated in the thyroid gland, kidneys, bladder, and stomach. HA was found to be concentrated in the vertebrae, joints, and salivary glands within 4 hours after a single dose. It is suggested by pharmacokinetic studies in animals that HA distributes into the lymphatic system.

According to a pharmacokinetic review, the volume of distribution of magnesium sulphate when used to manage patients with pre-eclampsia and eclampsia ranged from 13.65 to 49.00 L.

Elimination Route

There is limited information in the literature regarding the human absorption and pharmacokinetics of hyaluronic acid. When administered to rats in the oral form, hyaluronic acid is broken down to oligosaccharides by intestinal bacteria and absorbed in the colon. In pharmacokinetic studies of beagle dogs, HA was readily absorbed and rapidly excreted. When applied topically, HA with low molecular weight ranging from 20-300 kDa is absorbed through the stratum corneum, and HA with high molecular weight (1000-1400 kDa) does not penetrate the stratum corneum. The bioavailability of hyaluronic acid depends on its molecular weight.

Approximately 24-76% of ingested magnesium is absorbed in the gastrointestinal tract, primarily via passive paracellular absorption in the small intestine.

Half Life

When injected by the intra-articular route hyaluronic acid has a half-life ranging from 17 hours to 1.5 days. The half-life of hyaluronic acid is longer for purified or formulations or preparations with high molecular weight. It can vary according to the molecular weight of the administered HA, according to studies in animals. The metabolic half-life of hyaluronic acid in sheep was determined to be approximately 27 hours in pharmacokinetic studies. In sheep, HA is believed to undergo rapid elimination via the blood and liver.

Magnesiums biologic half-life is reported to be approximately 1000 hours or 42 days.

Clearance

There is limited information in the literature regarding the human pharmacokinetics of hyaluronic acid. In a pharmacokinetic study of rabbits, maximum clearance capacity of intravenously administered hyaluronic acid was about 30 mg/day/kg.

Elimination Route

There is limited information in the literature regarding the human pharmacokinetics of hyaluronic acid. Studies in rats and dogs administered a radio-labeled oral dose of HA showed 87-96% excretion the feces. Excretion of hyaluronic acid is primarily extra-renal, with some contribution from the spleen.

The majority of magnesium is excreted renally.

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