Rayvit Plus

Uses

Chromium is an ingredient found in a variety of supplements and vitamins.

Indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN), to maintain chromium serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms .

Copper is a transition metal found in a variety of supplements and vitamins, including intravenous solutions for total parenteral nutrition (TPN).

For use in the supplementation of total parenteral nutrition and in contraception with intrauterine devices .

Manganese is a transition metal used for supplementation of manganese during Total Parenteral Nutrition (TPN).

Indicated for use as a supplement to intravenous solutions given for Total Parenteral Nutrition (TPN). Administration helps to maintain plasma levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

Selenium is an ingredient found in a variety of supplements and vitamins.

For the supplementation of total parenteral nutrition to prevent hyposelenemia .

Zinc Sulphate is used for Recurrent Respiratory Tract Infections; Diarrhoea; Loss of appetite; Severe growth retardation; Deformed bone formation; Impaired immunological response; Acrodermatitis enteropathica; Parakeratatic skin lesions; Defective and delayed wound healing; Anaemia; Night blindness; Mental disturbances

Rayvit Plus is also used to associated treatment for these conditions: Mineral supplementationEmergency Contraception, IUD, Trace Element Deficiency, Dietary supplementationMineral supplementation, Total parenteral nutrition therapy, Vitamin supplementation, Dietary supplementationNutritional supplementation

How Rayvit Plus works

Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Its role in potentiating insulin signalling cascades has been implicated in several studies. Chromium upregulates insulin-stimulated insulin signal transduction via affecting effector molecules downstream of the insulin receptor (IR). IR-mediated signalling pathway involves phoshorylation of multiple intracellular domains and protein kinases, and downstream effector molecules . Upon activation by ligands, intracellular β-subunit of IR autophosphorylates and activates tyrosine kinase domain of the IR, followed by activation and phosphorylation of regulatory proteins and downstream signalling effectors including phosphatidylinositol 2-kinase (PI3K). PI3K activates further downstream reaction cascades to activate protein kinase B (Akt) to ultimately promote translocation of glucose transporter-4 (Glut4)-vesicles from the cytoplasm to the cell surface and regulate glucose uptake . Chromium enhances the kinase activity of insulin receptor β and increases the activity of downstream effectors, pI3-kinase and Akt.

Under insulin-resistant conditions, chromium also promotes GLUT-4 transporter translocation that is independent of activity of IR, IRS-1, PI3-kinase, or Akt; chromium mediates cholesterol efflux from the membranes via increasing fluidity of the membrane by decreasing the membrane cholesterol and upregulation of sterol regulatory element-binding protein . As a result, intracellular GLUT-4 transporters are stimulated to translocate from intracellular to the plasma membrane, leading to enhanced glucose uptake in muscle cells . Chromium attenuates the activity of PTP-1B in vitro, which is a negative regulator of insulin signaling. It also alleviates ER stress that is observed to be elevated the suppression of insulin signaling. ER stress is thought to activate c-Jun N-terminal kinase (JNK), which subsequently induces serine phosphorylation of IRS and aberration of insulin signalling . Transient upregulation of AMPK by chromium also leads to increased glucose uptake .

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2 . It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%).

Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor . It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor.

Copper appears to reduce the viabilty and motility of spermatozoa . This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect . The exact mechanism of copper's effect on sperm are unknown.

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA . This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality .

The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS) . The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein . Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function .

Dosage

Rayvit Plus dosage

Syrup-

• Children under 10 kg: One teaspoonful 2 times daily.
• Children within 10 to 30 kg: Two teaspoonful 1-3 times daily.
• Adults and children over 30 kg body weight: Four teaspoonful 1-3 times daily.

Tablet-In the treatment of Diarrhoea Zinc should be given as soon as diarrhoea starts:

• For infants between 2 to 6 months of age: 10 mg Zinc once daily for 10-14 days.
• For children between 6 months to 5 years of age: 20 mg Zinc once daily for 10-14 days.

For other indications:

• The recommended dose for children: 2 to 2.5 mg/kg/day.
• Children under 10 kg: 10 mg Zinc 2 times daily.
• Children within 10 to 30 kg: 20 mg Zinc 1-3 times daily.
• Adults and children over 30 kg body weight: 40 mg Zinc 1-3 times daily.

Dispersible Tablet-

• Place the tablet in a teaspoon
• Add adequate amount of water
• Let the tablet dissolve completely
• Give the entire spoonful solution

Side Effects

In case of zinc mild side effects such as gastric ulcer, nausea, vomiting, metallic taste, headache, drowsiness have been observed.

Toxicity

Oral LD50 for Cr (VI) is 135 - 175 mg/kg in mouse and 46 - 113 mg/kg in rat . Oral LD50 for Cr (III) in rat is >2000 mg/kg . LD50 of chromium (III) oxide in rats is reported to be > 5g/kg . Other LD50 values reported for rats include: 3.5 g/kg (CI 3.19-3.79 g/kg) for chromium sulphate; 11.3 g/kg for chromium (III) acetate; 3.3 g/kg for chromium nitrate; and 1.5 g/kg for chromium nitrate nonahydrate .

Acute overdose of chromium is rare and seriously detrimental effects of hexavalent chromium are primarily the result of chronic low-level exposure . In case of overdose with minimal toxicity following acute ingestion, treatment should be symptomatic and supportive . There is no known antidote for chromium toxicity.

Hexavalent chromium is a Class A carcinogen by the inhalation route of exposure and Class D by the oral route . The oral lethal dose in humans has been estimated to be 1-3 g of Cr (VI); oral toxicity most likely involves gastrointestinal bleeding rather than systemic toxicity . Chronic exposure may cause damage to the following organs: kidneys, lungs, liver, upper respiratory tract . Soluble chromium VI compounds are human carcinogens. Hexavalent chromium compounds were mutagenic in bacteria assays and caused chromosome aberrations in mammalian cells. There have been associations of increased frequencies of chromosome aberrations in lymphocytes from chromate production workers . In human cells in vitro, Cr (VI) caused chromosomal aberrations, sister chromatid exchanges and oxidative DNA damage .

Copper toxicity is belevied to be due to fenton-type redox reactions occuring with high copper concentrations which produce damaging reactive oxygen species .

Oral LD50 of 6700mg/kg in rats . Selenium exposure is teratogenic and can result in fetal death as tested in mice. Chronic toxicity is characterized by hair loss, white horizontal streaking on fingernails, paronchyia, fatigue, irritability, hyperreflexia, nausea, vomiting, garlic odor on breath, and metallic taste . Serum selenium correlates weakly with symtoms. Blood chemistry as well as liver and kidney function are normally unnaffected. Acute toxicity presents as stupor, respiratory depression, and hypotension. ST elevations and t-wave changes characteristic of myocardial infarction may be observed.

Precaution

Concurrent administration of Zinc salt with penicillamine might diminish the effect of Penicillamine. The absorption of Zinc, although poor, may be decreased by various compounds including some foods. Chelation may occur with tetracyclines.

Interaction

Zinc may inhibit the absorption of concurrently administered tetracyclines, when both are being given an interval of at least 3 hours.

Volume of Distribution

Absorbed chromium is distributed to all tissues of the body and its distribution in the body depends on the species, age, and chemical form . Circulating Cr (III) following oral or parenteral administration of different compounds can be taken up by tissues and accumulates in the liver, kidney, spleen, soft tissue, and bone .

Elimination Route

Chromium compounds are both absorbed by the lung and the gastrointestinal tract. Oral absorption of chromium compounds in humans can range between 0.5% and 10%, with the hexavalent (VI) chromium more easily absorbed than the trivalent (III) form . Absorption of chromium from the intestinal tract is low, ranging from less than 0.4% to 2.5% of the amount consumed . Vitamin C and the vitamin B niacin is reported to enhance chromium absorption .

Most hexavalent Cr (VI) undergoes partial intragastric reduction to Cr (III) upon absorption, which is an action mainly mediated by sulfhydryl groups of amino acids . Cr (VI) readily penetrates cell membranes and chromium can be found in both erythrocytes and plasma after gastrointestinal absorption of Cr (IV). In comparison, the presence of chromium is limited to the plasma as Cr (III) displays poor cell membrane penetration . Once transported through the cell membrane, Cr (VI) is rapidly reduced to Cr (III), which subsequently binds to macromolecules or conjugate with proteins. Cr (III) may be bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF).

Copper absorption varies inversely with intake. Absorption range is 12-65%.

Oral bioavailability of 90% when given as L-selenomethionine . Tmax of 9.17h.

Half Life

The elimination half-life of hexavalent chromium is 15 to 41 hours .

Half life was observed to increase with chronic dosing time . For day 1-2 half life was 1.7 days. For day 2-3 half life was 3 days. For day 3-14 half life was 11.1 days.

Clearance

Excretion of chromium is via the kidneys ranges from 3 to 50 μg/day . The 24-hour urinary excretion rates for normal human subjects are reported to be 0.22 μg/day .

Elimination Route

Absorbed chromium is excreted mainly in the urine, accounting for 80% of total excretion of chromium; small amounts are lost in hair, perspiration and bile . Chromium is excreted primarily in the urine by glomerular filtration or bound to a low molecular-weight organic transporter .

Copper appears to be eliminated primarily through bile .

Mainly excreted in urine as 1beta-methylseleno-N-acetyl-d-galactosamine and trimethylselenonium . The amount excreted as 1beta-methylseleno-N-acetyl-d-galactosamine plateaus at doses around 2microg after which the amount excreted as trimethylselenonium increases. Some selenium is also excreted in feces when given orally .

Pregnancy & Breastfeeding use

Pregnant women and nursing mothers should avoid zinc doses higher than RDA amounts.

Contraindication

It is contraindicated in patients with hypersensitivity to Zinc.

Acute Overdose

Zinc sulphate is corrosive in overdose. Symptoms are corrosion and inflammation of the mucous membrane of the mouth and stomach; ulceration of the stomach followed by perforation may occur. Gastric lavage and emesis should be avoided. Demulcents such as milk should be given. Chelating agents such as sodium edetate may be useful.

Storage Condition

Store in a cool place. The syrup should be protected from light.

Innovators Monograph

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