Synowell

Synowell Uses, Dosage, Side Effects, Food Interaction and all others data.

Chondroitin sulfate is a glycosaminoglycan considered as a symptomatic slow-acting drug for osteoarthritis (SYSADOA). The SYSADOA status suggested a pain relief and increased joint mobility after a relative long regular administration, as well as a long-lasting effect after the end of the treatment. Chondroitin sulfate is composed of alternating 1,3-N-acetyl-β-d-galactosamine and 1,4-β-d-glucuronic acid units which bear 4-O- and/or 6-O-sulfations at the N-acetylgalactosamine units disposed of in specific patterns. Depending on the predominating disaccharide unit, it will present different biological activities. Chondroitin sulfate is sold as an OTC dietary supplement in North America and it is a prescription drug under the EMA in Europe.

In clinical trials, chondroitin sulfate has been reported a significant pain relief. Some reports have shown no slow in joint damage. The effects of chondroitin sulfate have been very controversial. One of the characteristics of chondroitin is a slow onset of action with a maximal effect attained after several months. Chondroitin sulfate has been reported to have anti-inflammatory properties by reducing the synovitis and prevent proinflammatory cytokine up-regulation in arthritis models.

It is also registered an anabolic effect of chondroitin sulfate in which it induces the synthesis of hyaluronate in synovial cells, it increases type II collagen and proteoglycan synthesis.

Curcumin, also known as diferuloylmethane, is an active component in the golden spice turmeric (Curcuma longa) and in Curcuma xanthorrhiza oil. It is a highly pleiotropic molecule that exhibits antibacterial, anti-inflammatory, hypoglycemic, antioxidant, wound-healing, and antimicrobial activities . Due to these properties, curcumin has been investigated for the treatment and supportive care of clinical conditions including proteinuria, breast cancer, multiple myeloma, depression, and Non Small Cell Lung Cancer (NSCLC). Despite proven efficacy against numerous experimental models, poor bioavailability due to poor absorption, rapid metabolism, and rapid systemic elimination have been shown to limit the therapeutic efficacy of curcumin . Curcumin is under investigation for the treatment and supportive care of various clinical conditions including mucositis, rectal cancer, prostate cancer, chronic schizophrenia, and Mild Cognitive Impairment (MCI) .

Intravenous application of 25 mg/kg bw curcumin to rats resulted in an increase in bile flow by 80 and 120% . In the rat model of inflammation, curcumin was shown to inhibit edema formation. In nude mouse that had been injected subcutaneously with prostate cancer cells, administration of curcumin caused a marked decrease in the extent of cell proliferation, a significant increase of apoptosis and micro-vessel density . Curcumin may exert choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility . Curcumin inhibited arachidonic acid-induced platelet aggregation in vitro .

Glucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine stimulates the production of proteoglycans and increases sulfate uptake by articular cartilage.

The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.

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.

Synowell
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Synowell
Generic	Curcumin + Glucosamine + Hyaluronic Acid + Methylsulfonylmethane + Chondroitin Sulfate + Boswellin
Weight	50mg
Type	Tablet
Therapeutic Class
Manufacturer	Medicorp Pharmaceuticals
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Chondroitin sulfate, used with glucosamine, is indicated to alleviate pain and inflammation from primary osteoarthritis. This supplement is reported to improve joint function and slow disease progression. Osteoarthritis is characterized by progressive structural and metabolic changes in joint tissues, mainly cartilage degradation, subchondral bone sclerosis and inflammation of synovial membrane.

Studies have proposed the potential use of chondroitin sulfate as a nutraceutical in dietary supplements.

No approved therapeutic indications.

Indicated for the treatment of osteoarthritis of knee, hip, spine, and other locations. Also used as dietary supplement

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.

Synowell is also used to associated treatment for these conditions: Arthritis, Backache, Muscle Strain, Osteoarthritis (OA), Soreness, Muscle, Sprains, Eye lubrication, Joint supplementationArthritis, Backache, Joint Pain, Osteoarthritis (OA), Osteoarthritis of the KneeActinic 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 Synowell works

Chondroitin sulfate functions as a major component of the intricate extracellular matrix. It is proposed that chondroitin sulfate supply can provide new building blocks for the synthesis of new matrix components.

The anti-inflammatory effect of chondroitin sulfate is thought to be caused by the inhibition of the synthesis of inflammatory intermediates such as the inhibition of nitric oxide synthase, COX-2, microsomal prostaglandin synthase 1 and prostaglandin E2. It is reported also an inhibitory activity in the toll-like receptor 4 which will later inhibit inflammatory cytokines, NFkB and MyD88. This activity suggests a modulation of the MAP kinase pathway. On the other hand, some reports have pointed out an induction on the PKC/PI3K/Akt pathway in neuroblastoma.

The anabolic effect of chondroitin sulfate is suggested to be caused by the inhibition of metalloproteinases such as MMP-1, -3 and -13 as well as ADAMTS-4 and -5.

Curcumin acts as a scavenger of oxygen species, such as hydroxyl radical, superoxide anion, and singlet oxygen and inhibit lipid peroxidation as well as peroxide-induced DNA damage . Curcumin mediates potent anti-inflammatory agent and anti-carcinogenic actions via modulating various signalling molecules. It suppresses a number of key elements in cellular signal transduction pathways pertinent to growth, differentiation, and malignant transformation; it was demonstrated in vitro that curcumin inhibits protein kinases, c-Jun/AP-1 activation, prostaglandin biosynthesis, and the activity and expression of the enzyme cyclooxygenase (COX)-2 .

The mechanism of action of glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time.

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.

Dosage

Synowell dosage

500 mg tablet three times daily or as directed by the physician. A single dose of 1500 mg daily may also be effective. Obese individuals may need higher doses, based on body weight.

Side Effects

Safety studies with Glucosamine show no demonstrable toxicity. Rarely occurring side effects like mild & reversible intestinal flatulence are almost like placebo.

Toxicity

Chondroitin sulfate does not present a carcinogenic potential. On tolerability assays, it has been shown to present great safety and good tolerability without significant severe side effects.

In an acute oral toxicity study in mouse, LD50 was >2000 mg/kg . Single oral doses of curcumin at 1-5 g/kg bw induced no toxic effects in rats . There has been no cases of overdose reported .

The oral LD50 of glucosamine in rats is >5000 mg/kg. Symptoms of an overdose with glucosamine may include nausea, vomiting, abdominal pain, and diarrhea (common side effects of this drug). Severe and life-threatening hypersensitivity reactions to glucosamine may occur in patients with a shellfish allergy or asthma.

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.

Precaution

Diabetics are advised to monitor blood glucose levels regularly while taking Glucosamine. No special studies were formed in patients with renal and/or hepatic insufficiency. The toxicological and pharmacokinetic profile of the product does not indicate limitations for these patients. However, administration to these patients with severe hepatic or renal insufficiency should be under appropriate medical supervision.

Interaction

There have been no reports of significant drug interactions ofGlucosamine with antibiotics, antidepressants, antihypertensives, nitrates, antiarrhythmics, anxiolytic, hypoglycaemic agents, anti-secretives.

Volume of Distribution

After intramuscular administration of chondroitin sulfate, the apparent volume of distribution was 0.40 ml/g. When administered orally, the apparent volume of distribution changed to 0.44ml/g.

Following oral administration of radio-labelled curcumin to rats, radioactivity was detected in the liver and kidneys .

Results of a pharmacokinetic study of 12 healthy volunteers receiving three daily consecutive oral administrations of glucosamine sulfate soluble powder demonstrated glucosamine distribution to extravascular compartments. Human pharmacokinetic data for glucosamine is limited in the literature, however, a large animal model study of horses revealed a mean apparent volume of distribution of 15.4 L/kg. Concentrations of glucosamine ranged from 9-15 microM after an intravenous dose, and 0.3-0.7 microM after nasogastric dosing. These concentrations remained in the range of 0.1-0.7 microM in the majority of horses 12 hours after dosing, suggesting effectiveness of a once-daily dose. In rats and dogs, radioactivity from a C-14 labeled dose of glucosamine is detected in the liver, kidneys, articular cartilage, and other areas.

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

Chondroitin sulfate is absorbed from the gastrointestinal tract. The absorbed portion reaches a ratio of 10% as unchanged chondroitin sulfate and 90% as depolymerized low-molecular-weight derivatives. This absorption depends on the sulfation status. The bioavailability of chondroitin sulfate ranges from 10-20% following oral administration. Reports have shown a consistent accumulation of the compound in joint tissue. The steady-state is attained after 3-4 days and it takes around 3-6 months to obtain the maximal effect.

After intramuscular administration of chondroitin sulfate, the peak plasma level of 3.8 mcg/ml was reached after 90 min. When given orally, the peak plasma concentration of 4.6 mcg/ml was reached after 240 min.

Curcumin displays poor absorption into the gastrointestinal tract. In a rat study, oral administration of a single dose of 2 g of curcumin resulted in a plasma concentration of less than 5 μg/mL, indicating poor absorption from the gut .

In a pharmacokinetic study, glucosamine was 88.7% absorption by the gastrointestinal tract. Absolute oral bioavailability was 44%, likely due to the hepatic first-pass effect. In a pharmacokinetic study of 12 healthy adults receiving oral crystalline glucosamine, plasma levels increased up to 30 times the baseline levels and Cmax was 10 microM with a 1,500 mg once-daily dose. Tmax was about 3 hours. AUC was 20,216 ± 5021 after a 15,000 mg dose.

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 approximate half-life of chondroitin sulfate and its derivative metabolites is 15 hours. After intramuscular administration of chondroitin sulfate in humans, the elimination half-life of the chondroitin sulfate was of 275 min. When administered orally, the elimination half-life was presented at 310 min.

No pharmacokinetic data available.

The estimated half-life for glucosamine is 15 hours after an oral dose. After a bolus intravenous injection of 1005 mg crystalline glucosamine sulfate, the parent drug has an apparent half life of 1.11 hours.

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

No pharmacokinetic data available.

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

Chondroitin sulfate is excreted in the urine as intact polymers and as partial degradation products. After intramuscular administration, about 37% of the administered dose is excreted by urine during the first 24 hours as high- and low-molecular-weight derivatives.

Following oral administration of curcumin to rats at a dose of 1 g/kg bw, about 75% of dose was excreted in the faeces and only traces of the compound was detected in the urine . When a single 400 mg dose of curcumin was administered orally to rats, about 60% was absorbed and 40% was excreted unchanged in the faeces over an period of 5 days . Intraperitoneal administration resulted in fecal excretion of 73% and biliary excretion of 11% .

Fecal excretion of glucosamine in a pharmacokinetic study was 11.3% within 120 hours after administration. Urinary elimination was found to be 1.19% within the first 8 hours post-administration.

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.

Pregnancy & Breastfeeding use

Women who are pregnant or who could become pregnant should not supplement with glucosamine. Glucosamine has not been studied enough to determine their effects on a developing fetus. And no studies have evaluated the use of Glucosamine during pregnancy or lactation. It should be taken with caution and medical advice during pregnancy and lactation.