Defluxectable
Defluxectable Uses, Dosage, Side Effects, Food Interaction and all others data.
Dextran is a polysaccharide that differs from others in that its glucose units are joined together 1:6 glucoside links. The main chain of glucose has short branches at frequent intervals which are probably joined by 1:3 and 1:4 glucoside links. The chains can be composed of about 200,000 glucose units. Many bacteria, like Leuconostoc, can synthesize dextran from sucrose, and this activity is used commercially to obtain dextran.
Dextran 40 is a sterile, nonpyrogenic preparation of low molecular weight dextran (average mol. wt. 40,000) in 5% Dextrose Injection or 0.9% Sodium Chloride Injection. It is administered by intravenous infusion.
Dextran 75 is a complex branched glucan with an average molecular weight 75000 Daltons. It is produced from certain bacteria that with α-1,6 glycosidic linkages between glucose molecules and α-1,3 linkages between branches. When labelled with technetium Tc99m, dextran 75 is intravenously administered as an imaging agent to detect and diagnose conditions in the vascular compartment such as pericardial effusion or ventricular aneurysm.
Hyaluronic acid (HA) is an anionic, nonsulfated glycosaminoglycan found in connective, epithelial, and neural tissues; it was first isolated in 1934. Karl Meyer and John Palmer obtained glycosaminoglycan (GAG) from the bovine eye, giving it the name “hyaluronic acid”. HA is involved in many important physiological processes, including but not limited to wound healing, tissue regeneration, and joint lubrication. It demonstrates unique viscoelasticity, moisturizing, anti-inflammatory qualities, and other important properties that prove beneficial in various clinical applications.
HA is used in drug delivery systems for the treatment of cancer, ophthalmological conditions, joint conditions, and aesthetic imperfections. Several preparations of hyaluronic acid have been approved by the FDA and are available in oral, topical, and injectable forms. A popular use of hyaluronic acid in recent years is cosmetic injection due to its ability to minimize the appearance of wrinkles and aging-related skin imperfections.
HA has long-acting lubricant, shock absorbing, joint stabilizing, and water balancing properties. It is similar to the naturally occurring glycosaminoglycan (GAG) in joints. Hyaluronic acid works by acting as a lubricant and shock absorber, facilitating joint mobility and thereby reducing osteoarthritic pain. Hyaluronic acid has antioxidative, anti-inflammatory, and analgesic effects. The water-balancing properties and viscoelasticity of hyaluronic acid are beneficial in cosmetic injections, imparting volume and reducing the appearance of imperfections and wrinkles. Due to the abovementioned properties, HA has a protective effect on the eyes and cornea.
| Trade Name | Defluxectable |
| Generic | Dextran + Hyaluronic Acid |
| Type | Gel |
| Therapeutic Class | |
| Manufacturer | Dr Reddys Laboratories Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Dextran is a low molecular weight dextran used as an adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma, as well as the prophylaxis of venous thrombosis and pulmonary embolism during high-risk medical procedures.
Dextran is used as the restoration of blood mass during surgical interventions if there is hypovolemia due to trauma or dehydration. It is as well used after the presence of hemorrhage in cases of blood loss to a level inferior to 15% of the blood mass, if compatibility test cannot be completed or when blood lots need to be tested for pathogen detection. Dextran is also used for the prevention of profound postoperative venous thrombosis.
Dextran as well presents ophthalmic applications as solutions or ointments for the temporary relief of xerophthalmia or minor ocular irritations.
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.
Defluxectable is also used to associated treatment for these conditions: Blood Circulation Disorder, Capillary disorder, Dry Eyes, Ocular Irritation, Pulmonary Embolism, Pulmonary Embolism caused by procedures associated with a high incidence of thromboembolic complications, Shock, Thrombosis, Venous, Venous Thrombosis caused by procedures associated with a high incidence of thromboembolic complications, Thrombotic events, Plasma Volume Replacement, Priming fluid in pump oxygenators therapyActinic 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 Defluxectable works
In preclinical studies, the mechanism of action is thought to be related to the blockage of the uptake of tissue plasminogen activator by mannose-binding receptors. This process has a direct effect by enhancing endogenous fibrinolysis.
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
Some reports have shown adverse effects when used in therapeutical doses and some teratogenic effects have been demonstrated when used in large doses. The current LD50 reported in rats is 10700 mg/kg.
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
The reported volume of distribution of dextran suggested a distribution throughout the blood volume. This volume of distribution is reported to be of around 120 ml. The organ that presented a higher accumulation of dextran was the liver.
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
Dextran presents a very low oral bioavailability that is reduced as the chain gets longer. Thus, the bioavailability of dextran is inversely proportional to the length of the carbohydrate chain.
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
The elimination half-life will depend on the length of the carbohydrate chain. The higher the molecular weight of the dextran the longer it will be the elimination half-life. The half-life will go from 1.9 hours from dextran 1 to 42 hours in the case of dextran 60.
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
The elimination of dextran will depend on the length of the carbohydrate chain, the administration route, and the molecular weight. For dextran 1, it is reported to be mainly secreted unchanged in the urine in a ratio of 80% of the administered dose when administered parentally. It is registered that the weight threshold for unrestricted glomerular filtration is about 15 kDa and if the dextran overpasses 50 kDa it will not be renally eliminated in any significant amount.
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.
Innovators Monograph
You find simplified version here Defluxectable
