Ligamento

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.

Ligamento 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 Healing

How Ligamento 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.

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.

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.

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.

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.

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.

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