Ocuclin

Uses

Methylcellulose is a compound used as a bulk forming laxative and is not an approved medication.

Solutions containing methyl cellulose are used as substitute for tears or saliva if the natural production of these fluids is disturbed. It is also used or constipation, diverticulosis, hemorrhoids and irritable bowel syndrome. Used in the manufacture of capsules in nutritional supplements. Its edible and nontoxic properties provide a vegetarian alternative to the use of gelatin.

Naphazoline is a sympathomimetic vasoconstrictor used for the symptomatic relief of redness and itching of the eye, and nasal congestion.

Naphazoline is indicated for use as OTC eyedrops for ocular vasoconstriction or as a nasal preparation for nasal congestion.

Zinc is an essential element commonly used for the treatment of patients with documented zinc deficiency.

Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .

Ocuclin is also used to associated treatment for these conditions: Constipation, Dry Eye Syndrome (DES), Eye disinfectionBacterial Conjunctivitis, Blepharoconjunctivitis, Conjunctivitis, Conjunctivitis allergic, Dacryocystitis, Dacryostenosis, Dermatitis, Eczematous of the Eyelid, Eye Pain, Eye redness, Iritis, Lacrimation, Nasal Allergies, Nasal Congestion, Noninfective conjunctivitis, Otitis Media (OM), Photophobia, Foreign body sensation in eye, Ocular bacterial infections, Ocular vasoconstrictionCandidiasis, Common Cold, Diaper Dermatitis, Diaper Rash, Eye redness, Iron Deficiency (ID), Ocular Irritation, Skin Irritation, Sunburn, Wilson's Disease, Zinc Deficiency, Dietary and Nutritional Therapies, Dietary supplementation

How Ocuclin works

Methylcellulose absorbs water in the gastrointestinal lumen thereby increasing the bulk of the stool. This leads to distension and stimulation of peristalsis. The ability of methylcellulose to absorb water may contribute to its efficacy in the management of diarrhea by once again increasing the bulk and consistency of the stool.

Naphazoline is a vasoconstrictor that functions by stimulating alpha adrenergic receptors in arterioles leading to decreased congestion at the site of administration.

Naphazoline causes the release of norepinephrine in sympathetic nerves. Norepinephrine binds to alpha adrenergic receptors and causes vasoconstriction. Naphazoline is also a mild beta adrenergic receptor agonist, which can cause rebound vasodilation after the alpha adrenergic stimulation has ended. Naphazoline's release of norepinephrine also triggers a negative feedback loop which decreases production of norepinephrine, which can lead to rhinitis medicamentosa after long term use when naphazoline is stopped.

Zinc has three primary biological roles: catalytic, structural, and regulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .

Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .

In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .

There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .

Zinc deficiency in humans decreases the activity of serum thymulin (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans [A342417].

The change of Th(1) to Th(2) function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells [A3424].

In humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .

In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers [A3424]. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .

The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .

Toxicity

Organism: Mouse Test type: LD50 Route : Intraperitoneal Reported Dose: 275gm/kg ( 275000mg/kg) Toxic Effect: Details of toxic effects not reported other than lethal dose value

Organism: Mouse Test type: LDLo Route : Intravenous Reported Dose: 1gm/kg ( 1000mg/kg) Toxic Effect: Details of toxic effects not reported other than lethal dose value

In high doses or when ingested, naphazoline can lead to central nervous system depression (which can progress to coma and death), hypothermia, bradycardia, and death. This effect is especially pronounced in children under 6 years.

Long term use of naphazoline can lead to rhinitis medicamentosa once naphazoline is stopped. This condition is a result of norepinephrine release by naphazoline triggering a negative feedback loop.

Safety and effectiveness in children under 12 has not been established. Studies in elderly patients have yet to be performed. Risk in pregnancy, breast feeding, and on overall fertility have not been established, though pregnant and breast feeding patients should consider the risk and benefit before starting naphazoline treatment.

According to the Toxnet database of the U.S. National Library of Medicine, the oral LD50 for zinc is close to 3 g/kg body weight, more than 10-fold higher than cadmium and 50-fold higher than mercury .

The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been measured in rats and mice .

Volume of Distribution

accumulation in liver, spleen, lymph nodes, kidney, and vascular walls.

Distribution data for naphazoline are scarce but imidazoline compounds are distributed throughout the body, and can cross the blood-brain barrier.

A pharmacokinetic study was done in rats to determine the distribution and other metabolic indexes of zinc in two particle sizes. It was found that zinc particles were mainly distributed to organs including the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender .

Elimination Route

Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur.

Absorption data for naphazoline are scarce but imidazoline compounds in general are weakly basic and lipophilic, with high bioavailability from the gastrointestinal tract.

Zinc is absorbed in the small intestine by a carrier-mediated mechanism . Under regular physiologic conditions, transport processes of uptake do not saturate. The exact amount of zinc absorbed is difficult to determine because zinc is secreted into the gut. Zinc administered in aqueous solutions to fasting subjects is absorbed quite efficiently (at a rate of 60-70%), however, absorption from solid diets is less efficient and varies greatly, dependent on zinc content and diet composition .

Generally, 33% is considered to be the average zinc absorption in humans . More recent studies have determined different absorption rates for various populations based on their type of diet and phytate to zinc molar ratio. Zinc absorption is concentration dependent and increases linearly with dietary zinc up to a maximum rate [L20902].

Additionally zinc status may influence zinc absorption. Zinc-deprived humans absorb this element with increased efficiency, whereas humans on a high-zinc diet show a reduced efficiency of absorption .

Half Life

4.2 minutes

Half life has not been determined but effects last for 4 to 8 hours. Other imidazoline compounds have half lives varying from 2 to 12 hours.

The half-life of zinc in humans is approximately 280 days .

Clearance

Clearance data for naphazoline is unavailable.

In one study of healthy patients, the clearance of zinc was found to be 0.63 ± 0.39 μg/min .

Elimination Route

When swallowed they are not absorbed to any appreciable degree and appear unchanged in feces.

Imidazoline compounds undergo some hepatic metabolism but a large fraction of the dose may be excreted unchanged in the urine. Urinary excretion is higher with more acidic urine.

The excretion of zinc through gastrointestinal tract accounts for approximately one-half of all zinc eliminated from the body .

Considerable amounts of zinc are secreted through both biliary and intestinal secretions, however most is reabsorbed. This is an important process in the regulation of zinc balance. Other routes of zinc excretion include both urine and surface losses (sloughed skin, hair, sweat) .

Zinc has been shown to induce intestinal metallothionein, which combines zinc and copper in the intestine and prevents their serosal surface transfer. Intestinal cells are sloughed with approximately a 6-day turnover, and the metallothionein-bound copper and zinc are lost in the stool and are thus not absorbed .

Measurements in humans of endogenous intestinal zinc have primarily been made as fecal excretion; this suggests that the amounts excreted are responsive to zinc intake, absorbed zinc and physiologic need .

In one study, elimination kinetics in rats showed that a small amount of ZnO nanoparticles was excreted via the urine, however, most of the nanoparticles were excreted via the feces .

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