Acnerid

Uses

Allantoin is an ingredient used in skin care products to relieve irritation and protect minor cuts, scrapes, and burns.

Allantoin is commonly applied in a variety of topical vehicles or applications such as cosmetic creams, toothpastes, mouthwashes, shampoos, lipsticks, anti-acne products, and lotions for the purpose of moisturizing skin, enhancing the smoothness of skin, stimulating the healing of wounds, and soothing irritated skin .

Indicated for topical use to help protect against infection in minor cuts, scrapes, and burns. No FDA-approved therapeutic indications.

Triclosan is an antimicrobial agent in clinical setting for disinfection, and prevention of spread and growth of bacteria, fungus, and mildew.

Triclosan is used in a variety of common household products, including soaps, mouthwashes, dish detergents, toothpastes, deodorants, and hand sanitizers. It is also used in health care settings in surgical scrubs and personnel hand washes.

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 .

Acnerid is also used to associated treatment for these conditions: Scarring, Dental cleaning, Skin Lightening, Skin protectionAcne, Dental Cavity, Dermabrasion, Gingivitis, Oral Infection, Plaque, Dental, Skin Infections, Bacterial, Abrasions, Minor burns, Antibacterial therapy, Antibiotic pre-surgical prophylaxisCandidiasis, 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 Acnerid works

There is no well controlled data that can formally substantiate the method of action . However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin . This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration .

The components of tea tree oil, particularly terpinen-4-ol and α-terpineol, mediate antimicrobial actions by disrupting the structural and functional integrity of bacterial membrane. Hydrocarbons are capable of partitioning into the cell and cytoplasmic membrane of microorganisms and disrupt their vital functions, which may result in leakage of ions such as potassium, and the inhibition of respiration . Eventually, cell lysis may occur due to weakening of the cell wall, and loss of turgor pressure and subsequent rupture of the cytoplasmic membrane . The loss of 260-nm-absorbing material may be indicative of a damaged cytoplasmic membrane and loss of nucleic acids . In E. coli, perturbed potassium homeostasis, glucose-dependent respiration, cell morphology, and ability to exclude propidium iodide was observed.

Tea tree oil also mediates its antifungal actions in a similar way, where it alters the permeability of Candida albicans and inhibits its respiration in a dose-dependent manner . Plasma and mitochondrial membranes of fungal species are also thought to be negatively affected by inhibition of glucose-induced medium acidification by tea tree oil, which involves inhibition of membrane ATPase responsible for the expulsion of protons . Tea tree oil also inhibits the formation of germ tubes, or mycelial conversion, in C. albicans, thereby disrupting cell morphogenesis . Water-soluble fraction of TTO, terpinen-4-ol, and α-terpineol, can inhibit the lipopolysaccharide-induced production of the inflammatory mediators such as TNF-α, IL-1β and IL-10 by human peripheral monocytes by approximately 50% and that of prostaglandin E2 by about 30% after 40 h . These components of tea tree oil may also suppress superoxide production by agonist-stimulated monocytes and decrease the production of reactive oxygen species by both stimulated neutrophils and monocytes .

Triclosan is a biocidal compound with multiple targets in the cytoplasm and membrane. At lower concentrations, however, triclosan appears bacteriostatic and is seen to target bacteria mainly by inhibiting fatty acid synthesis. Triclosan binds to enoyl-acyl carrier protein reductase enzyme (ENR). This complex has increased affinity for NAD+ and forms a ternary complex. This complex is unable to participate in fatty acid synthesis, weakening the cell membrane and causing cell death. Humans do not have an ENR enzyme, and thus are not affected.

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

No studies on repeated dose toxicity and reproductive toxicity have been submitted. Moreover, studies show that the tumor incidence in allantoin treated animals did not differ largely from that found in untreated controls. As a result, further or additional toxicity, mutagenicity, or carcinogenicity tests are not required in view of the endogenous nature of allantoin and the general lack of overall toxicity .

Finally, as allantoin is a normal component of the diet in humans and is a substance of endogenous origin present in the body of humans, it is generally recognized as being a safe substance for humans .

The 50% lethal dose for TTO in a rat model is 1.9 to 2.6 mL/kg, and doses ≤1.5 g/kg was associated with ataxia and lethargy. Dermal patches containing 10% of tea tree oil was not associated with any irritant reactions. Topically-applied tea tree oil rarely causes systemic toxicity . Dermal application of approximately 120 ml of undiluted tea tree oil to three cats with shaved but intact skin resulted in symptoms of hypothermia, uncoordination, dehydration, and trembling and in the death of one of the cats .

Oral LD50, Rat: 3700 mg/kg; Dermal LD50, Rabbit: 9300 mg/kg

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

No pharmacokinetic data available.

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

In studies on human subjects, a recovery of 19% and 34% of allantoin in the urine was observed but only in two individuals and only after the administration of massive doses of allantoin . After intravenous administration, recovery in the urine was practically quantitative with doses of 75 to 600 mgm in the human model . After 240 mgm, excretion continued for 72 hours in human subjects and the results were similar in regards to subcutaneous injection .

No pharmacokinetic data available.

A study conducted in 2000 demonstrated that low amounts of triclosan can be absorbed through skin and can enter the bloodstream. [PMID: 10722890] Triclosan is rapidly absorbed and distributed in the human body (Sandborgh-Englund et al., 2006). Maximum concentrations are reached within three hours after oral intake. However, the metabolism and excretion of the compound is fast.

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

When studied in cattle, sheep, and horses, the half-life of allantoin is in the range of 1 to 2.5 hours .

No pharmacokinetic data available.

The terminal plasma half life of triclosan is 21 h (Sandborgh-Englund et al., 2006).

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

Clearance

Some studies suggest that the average renal clearance of allantoin in normal, healthy human subjects is approximately 123 cc per minute . It is generally agreed upon that exogenously administered allantoin is rapidly excreted .

No pharmacokinetic data available.

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

Elimination Route

Urinary clearance is the predominant excretion route .

No pharmacokinetic data available.

In one study, after in vivo topical application of a 64.5mM alcoholic solution of [(3)H]triclosan to rat skin, 12% radioactivity was recovered in the faeces, 8% in the carcass 1% in the urine, 30% in the stratum corneum and 26% was rinsed from the skin surface at 24 hours after application. [PMID: 10722890]

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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