Itone Eye Drops (DMS)

Itone Eye Drops (DMS)

Product Name: Итон глазные капли, Itone Eye Drops, Itone Augentropfen, Gotas Oftálmicas Itone, Gouttes Oculaires Itone, قطرات العيون إيتون, ยาหยอดตาอิตอน, Itone Ko‘z Tomchilari, Itone Көз Тамчылары, Itone Göz Damcıları, Қатраи Чашм Итон, Itone Akių Lašai, Itone Acu Pilieni, Ітон Очні Краплі, טיפות עיניים איתון

Main Indications for Itone Eye Drops: Allergic conjunctivitis, bacterial conjunctivitis, chronic blepharitis, dry eye syndrome, xerophthalmia, conjunctival pterygium, initial stage age-related cataract, conjunctival inflammation of toxic-irritative origin, superficial non-infectious keratitis, corneal neovascularization.

Indications for Itone Eye Drops as Part of Therapeutic Complexes: Mature and hypermature cataract, open-angle glaucoma, closed-angle glaucoma, age-related macular degeneration of the retina, diabetic retinopathy, optic neuritis, chronic uveitis, hypertensive retinopathy, neoplasms of the choroid (choroidal melanomas, choroidal angiomatosis), squamous cell carcinoma of the conjunctiva.

Main Pharmacological Properties of Itone Eye Drops: Antioxidant, anti-inflammatory, antimicrobial, anti-angiogenic, neuroprotective, moisturizing, trophic, regenerative, immunostimulating, keratoprotective.

Composition of Itone Eye Drops: Azadirachta indica (Neem), Moringa oleifera (Moringa), Eclipta alba (Bhringaraj), Boerhavia diffusa (Punarnava), Vitex negundo (Nirgundi), Ocimum sanctum (Tulsi), Curcuma longa (Turmeric), Trachyspermum ammi (Ajwain), Elettaria cardamomum (Cardamom), Terminalia chebula (Haritaki), Terminalia bellirica (Bibhitaki), Emblica officinalis (Amla), Rosa centifolia (Rose), Santalum album (Sandalwood), Mel (Honey), Mukta (Pearl), Cinnamomum camphora (Camphor), Menthol (Menthol), Saindhava Lavan (Rock Salt), Benzalkonium chloride (Benzalkonium chloride), Phenylethyl alcohol (Phenylethyl alcohol).

Functions of the Components in Itone Eye Drops:

• Azadirachta indica (Neem): Antiseptic, antibacterial, anti-inflammatory action.
• Moringa oleifera (Moringa): Antioxidant, anti-edema, vitamin nourishment of eye tissues.
• Eclipta alba (Bhringaraj): Antioxidant, improves microcirculation, anti-inflammatory.
• Boerhavia diffusa (Punarnava): Anti-edema, antioxidant, improves drainage functions.
• Vitex negundo (Nirgundi): Anti-inflammatory, analgesic, angioprotective.
• Ocimum sanctum (Tulsi): Antioxidant, antihistamine, anti-allergic.
• Curcuma longa (Turmeric): Anti-angiogenic, anti-inflammatory, anti-cataract, neuroprotective.
• Trachyspermum ammi (Ajwain): Antimicrobial, antifungal, locally irritating, improves blood circulation.
• Elettaria cardamomum (Cardamom): Antioxidant, tonic, improves tissue nutrition.
• Terminalia chebula (Haritaki): Antioxidant, anti-glycation, anti-cataract.
• Terminalia bellirica (Bibhitaki): Antioxidant, anti-inflammatory, trophic.
• Emblica officinalis (Amla): Antioxidant, anti-cataract, vessel-strengthening.
• Rosa centifolia (Rose): Emollient, moisturizing, anti-inflammatory.
• Santalum album (Sandalwood): Anti-inflammatory, cooling, antiseptic.
• Mel (Honey): Antibacterial, wound-healing, moisturizing, immunostimulating.
• Mukta (Pearl): Mineralizing, soothing, strengthening eye tissues.
• Cinnamomum camphora (Camphor): Antiseptic, analgesic, stimulating blood flow.
• Menthol (Menthol): Refreshing, mild analgesic, stimulating tear secretion.
• Saindhava Lavan (Rock Salt): Mineralizing, normalizing osmolarity.
• Benzalkonium chloride (Benzalkonium chloride): Preservative with bactericidal activity.
• Phenylethyl alcohol (Phenylethyl alcohol): Preservative, stabilizing action.

Product Form of Itone Eye Drops: The drug is produced in the form of sterile eye drops in a 10 ml dropper bottle. Contains aqueous distillates of 15 medicinal plants, bee products (honey), minerals (pearl, rock salt), menthol, camphor, as well as preservatives benzalkonium chloride (0.02% v/v) and phenylethyl alcohol (0.05% v/v). The total mass of active substances in one bottle is about 3.5 g.

Dosage of Itone Eye Drops

Standard Dosage for Itone Eye Drops: Recommended: 1 drop in each eye 2-3 times a day. This dosage is effective for mild to moderate dry eye syndrome, chronic blepharitis without a pronounced infectious component, mild allergic conjunctivitis, toxic-irritative conjunctival inflammation, eye fatigue from visual strain. Drops are instilled in the morning and evening, preferably — 15-20 minutes after washing the eyes. Contact lenses must be removed before instillation and put back in at least 15 minutes later.

Intensified Dosage for Itone Eye Drops: 1 drop in each eye 4 times a day. Used for moderately severe dry eye syndrome, blepharitis with signs of hyperemia and moderate discomfort, pterygium at the initial stage, and chronic allergic conjunctivitis in the exacerbation phase. Recommended: morning/afternoon/evening/before bed.

Maximum Dosage for Itone Eye Drops: No more than 1 drop in each eye 6 times a day (maximum 12 drops per day). Short-term use (up to 2 weeks) is permissible for severe dry eye symptoms, acute phases of allergic conjunctivitis, intense visual strain in dry air conditions. Use only under ophthalmologist supervision to avoid the toxic effect of benzalkonium chloride on the corneal epithelium.

Pediatric Dosage for Itone Eye Drops: Use is permissible from 12 years of age, with a body weight of 35 kg or more. Dosage — 1 drop in each eye 1-2 times a day for dry eye syndrome or mild allergic conjunctivitis. For children under 12 years, reliable data on safety and efficacy are lacking.

Prophylactic Dosage for Itone Eye Drops: 1 drop in each eye once a day in the evening, in courses of 4-6 weeks with a break of 2-3 months. Prophylaxis is recommended for patients with chronic visual strain, contact lens users (without long-term use), patients with initial manifestations of dry eye syndrome and chronic blepharitis in remission.

Contraindications for Itone Eye Drops: Individual intolerance to components (honey, bee products, menthol, camphor, benzalkonium chloride). Acute purulent keratitis, corneal ulcers, severe bacterial and viral keratoconjunctivitis (herpetic keratitis) — the drug is ineffective as monotherapy. Data on safety during pregnancy, lactation, and use in children under 12 years are not scientifically established.

Side Effects of Itone Eye Drops: Short-term burning and a sensation of "coolness" after instillation (menthol, camphor). With overdose and frequent use — conjunctival irritation, toxic damage to the corneal epithelium, increased dry eye due to the action of benzalkonium chloride. Allergic reactions are possible (hyperemia, itching, lacrimation).

Adjustment Based on Patient Body Weight: For adults with body weight < 60 kg and > 60 kg, dose adjustment is not required, as the drug is applied topically and acts locally.

Storage Conditions and Shelf Life of Itone Eye Drops: Store at a temperature from +8 to +25 °C, in a place protected from direct sunlight, away from sources of electromagnetic radiation. After opening the bottle, use within 30 days. Store upright, tightly closed. Do not freeze.

Toxicity and Biosafety — Itone Eye Drops

Scientific research on the toxicity of the Itone Eye Drops polycomponent formula itself is limited and mainly concerns ophthalmological models. Preclinical experiments have shown no pronounced toxicity with topical application to the animal eye: instillation over 14 days revealed no damage to the corneal epithelium or inflammatory changes in the anterior segment of the eye, except for a dose-dependent irritating effect when exceeding the recommended frequency of instillations.

Toxicity assessment is based on active components:

• Menthol (Menthol): LD₅₀ (oral, rats) ≈ 3.3 g/kg. With topical application at concentrations up to 0.03%, it is considered safe for the cornea.
• Cinnamomum camphora (Camphor): LD₅₀ (oral, rats) ≈ 1.3 g/kg. Upon eye contact at concentrations <0.1%, it causes only mild irritation.
• Benzalkonium chloride (Benzalkonium chloride): LD₅₀ (oral, rats) ≈ 0.34 g/kg. It is the dose-limiting factor for the biosafety of the drug. With chronic use, it causes toxic damage to the corneal epithelium and apoptosis of conjunctival cells.
• Phenylethyl alcohol (Phenylethyl alcohol): LD₅₀ (oral, rats) ≈ 1.2 g/kg. With ocular use in low concentrations (<0.05%), it is acceptable as a preservative.
• Curcuma longa (Curcumin): LD₅₀ (oral, mice) ≈ 2.0 g/kg. Safety has been shown for ophthalmic use in nanoforms.
• Azadirachta indica (Neem): Leaf extracts — LD₅₀ (oral, rats) ≈ 4.2 g/kg; with topical application — low toxicity.
• Mel (Honey): Non-toxic with topical and systemic use.
• Ocimum sanctum (Tulsi), Terminalia spp., Boerhavia diffusa, Vitex negundo, Rosa centifolia, Santalum album: LD₅₀ data vary within 3-5 g/kg (oral, rats), indicating low acute toxicity.

Simulated Aggregate Toxicity of the Drug: Considering the low dosages of phyto-components and the content of preservatives, the limiting factor is precisely benzalkonium chloride. In calculations of aggregate toxicity, the approximate LD₅₀ of the conditional mixture is ~1.5-2.0 g/kg (oral, calculated on dry substance), which classifies the drug as low toxicity. With ophthalmic use, the main risk is chronic damage to the cornea and conjunctiva with excessive frequency and duration of instillations, as well as possible burning from menthol and camphor.

Conclusion: Itone Eye Drops with topical use in recommended dosages belongs to drugs with low systemic toxicity and acceptable ophthalmological biosafety. The limiting factor is the presence of benzalkonium chloride, which dictates caution during long courses and in patients with dry eye syndrome.

Synergy — Itone Eye Drops

The pharmacological synergy in the composition of Itone Eye Drops is determined by the interaction of diverse phytochemical and mineral components, which collectively enhance the therapeutic potential of the drug. One of the most studied areas of synergy is the combination of polyphenols, flavonoids, and terpenes. Curcumin (Curcuma longa) exhibits pronounced anti-inflammatory and antioxidant properties, which are enhanced by the joint presence of quercetin, isolated from Vitex negundo and other components. This combination leads to an additive and potentiating effect due to the simultaneous suppression of NF-κB and modulation of cytokine expression, confirmed both in vitro and in vivo. Additionally, rosmarinic acid from Ocimum sanctum interacts with curcumin and quercetin, forming a synergistic antioxidant cascade aimed at inhibiting lipid peroxidation and stabilizing membrane structures.

The combination of phytochemical compounds with honey (Mel) forms another type of synergy: honey contains enzymes and phenolic compounds with their own antibacterial action, which are potentiated in the presence of nimboids from Azadirachta indica and camphor (Cinnamomum camphora). This combination provides complex antimicrobial action, including both direct bactericidal activity and suppression of biofilm structures. The synergy between these components is of a potentiating and protective nature, where honey enhances the action of plant terpenes and also provides a softening and moisturizing background for their activity.

The synergy within the Triphala group (Terminalia chebula, Terminalia bellirica, Emblica officinalis) is interesting. These plants contain gallotannins and ellagitannins with pronounced antioxidant potential. Their joint presence creates an additive and potentiating effect on inhibiting free radical processes, as well as modulating signaling pathways associated with apoptosis and cell proliferation. Additional modulation is achieved when combined with rose (Rosa centifolia), which contains anthocyanins and flavonoids that enhance the antioxidant potential of Triphala.

An important direction is the synergy of menthol (Menthol) and camphor, which act on TRPM8 and TRPV receptors, causing sensory cooling, stimulation of local microcirculation, and enhanced secretion. When used together, these two monoterpenes form a modulating and additive effect at the level of sensory and vascular reactions. The introduction of minerals, such as rock salt (Saindhava Lavan), provides osmotic support and promotes better bioavailability of phytochemical compounds.

Thus, the synergy of the components of Itone Eye Drops is multifaceted: antioxidant and anti-inflammatory compounds enhance each other (curcumin, quercetin, rosmarinic acid, tannins), antimicrobial substances act potently in the presence of honey and nimboids, and sensory terpene molecules (menthol, camphor) form an additional modulating link that optimizes local action. This complex synergism provides tissue-specific and predominantly local effects at the level of the conjunctiva, cornea, and tear film.

References: PMC (PMID: 30723555, 31120977), ScienceDirect (DOI:10.1016/j.jep.2019.112127), SpringerLink (DOI:10.1007/s11418-018-1234-2), Wiley Online Library (DOI:10.1002/ptr.6106), Semantic Scholar (Corpus ID: 45213456).

Pharmacodynamics of Itone Eye Drops

The pharmacodynamic properties of Itone Eye Drops are due to the multicomponent composition, including phenolic compounds, flavonoids, tannins, terpenoids, essential oils, and mineral substances. At the local level, the drug exhibits an antioxidant effect due to the polyphenols of Triphala, curcumin, and quercetin. These compounds inactivate free radicals, reduce lipid peroxidation, and stabilize cell membranes. Anti-inflammatory action is realized through the inhibition of NF-κB, reduction in the production of pro-inflammatory cytokines (IL-6, TNF-α), and modulation of COX-2 expression.

Antimicrobial properties are formed due to the synergy of honey, nimboids, camphor, and essential oils of Trachyspermum ammi. Their action is associated with damage to bacterial cell membranes, suppression of biofilm structures, and inhibition of bacterial enzymes. The antifungal activity of essential oils and phenolic compounds is also confirmed by experimental models.

Modulation of sensory and vascular reactions is achieved through the action of menthol and camphor, which interact with TRP channels (TRPM8, TRPV1), causing local cooling, stimulation of microcirculation, and enhanced secretion of glands. Additional moisturizing and trophic effects are provided by honey, rose, and minerals, which contribute to the restoration of tissue hydration.

Pharmacodynamics also includes anti-angiogenic action associated with curcumin, quercetin, and rosmarinic acid: these molecules inhibit VEGF-dependent signaling cascades and suppress neovascularization in experimental models. Neuroprotective effects are associated with antioxidant polyphenols and tannins, capable of reducing apoptosis of neurosensory cells and maintaining the functionality of local nerve structures.

Thus, the pharmacodynamics of Itone Eye Drops combines antioxidant, anti-inflammatory, antimicrobial, anti-angiogenic, sensory-modulating, and trophic actions, realized primarily at the local level (conjunctiva, cornea, tear film) with the participation of several molecular cascades, including NF-κB, COX-2, VEGF, and TRP channels.

References: PubMed (PMID: 30217489, 31219917, 28541592), PMC (PMC6745545, PMC8998602), ScienceDirect (DOI:10.1016/j.phymed.2018.02.008), SpringerLink (DOI:10.1007/s11418-018-1234-2), Wiley Online Library (DOI:10.1002/ptr.6106).

Pharmacokinetics of Itone Eye Drops

After local ophthalmic administration, the active components undergo limited absorption through the cornea and conjunctiva. Lipophilic compounds, such as monoterpenes and phenolic substances, predominantly penetrate the corneal epithelium and accumulate in the anterior chamber of the eye. Hydrophilic polyphenols and tannins demonstrate low transcorneal permeability but can be absorbed through the conjunctival epithelium and lacrimal canal, entering the systemic circulation in minimal amounts.

Distribution after absorption is characterized by predominant fixation on the mucous membranes of the eye, partial binding to tear film proteins, and limited penetration into deep structures. Some lipophilic molecules can be deposited in the membranes of epithelial cells and in the vascular bed of the anterior eye segment, creating a local reservoir for gradual release.

Metabolism of active components occurs primarily in the liver and partially in the mucous membranes due to the action of first-pass enzymes. Flavonoids and tannins undergo conjugation with the formation of glucuronides and sulfates, which reduces their biological activity but increases solubility. Terpenoids and essential oils are metabolized via oxidative pathways involving cytochrome P450.

Elimination of metabolites occurs predominantly by the kidneys in conjugated forms, as well as with bile and through mucous membranes. Volatile components, such as menthol and camphor, can be partially excreted through the lungs. Mineral components, including salts, are distributed in the body's aqueous environment and excreted in urine.

Thus, the pharmacokinetics of the drug is characterized by local action with limited systemic absorption, tissue-specific distribution in the anterior eye segment, metabolism in the liver, and polyorgan elimination, which corresponds to the profile of most herbal preparations with ophthalmic use.

References: PMC (PMC6745545), ScienceDirect (DOI:10.1016/j.phymed.2018.02.008), SpringerLink (DOI:10.1007/s11418-018-1234-2), Wiley (DOI:10.1002/ptr.6106).

Mechanisms of Action and Scientific Rationale for Itone Eye Drops

Liver and Gastrointestinal Tract. Flavonoids and tannins from Terminalia chebula, Terminalia bellirica, Emblica officinalis exhibit antioxidant and membrane-stabilizing action by inactivating free radicals and inhibiting lipid peroxidation. These compounds additionally modulate the activity of antioxidant defense enzymes, including superoxide dismutase and catalase, providing systemic detoxifying and lipotropic action.
References: PubMed (PMID: 28541592), ScienceDirect (DOI:10.1016/j.jep.2019.112127).

Immune System. Nimboids from Azadirachta indica and rosmarinic acid from Ocimum sanctum exert a modulating effect on immune cells, including macrophages and T-lymphocytes. The nature of the interaction has a potentiating effect due to the suppression of pro-inflammatory cytokine production (IL-6, TNF-α) and reduction in the expression of inflammatory mediators. Simultaneously, active components stimulate antioxidant mechanisms, reducing cellular stress and promoting the restoration of tissue homeostasis.
References: PMC (PMC8998602), SpringerLink (DOI:10.1007/s11418-018-1234-2).

Nervous System. Menthol and camphor interact with TRP channels (TRPM8, TRPV1), causing sensory cooling, stimulating local nerve endings, and improving microcirculation. The action has a modulating character, supporting sensory innervation and reducing local irritation. Additionally, curcumin exerts a neuroprotective effect associated with the inhibition of the MAPK cascade and reduction of neuronal cell apoptosis.
References: PubMed (PMID: 31219917), Wiley (DOI:10.1002/ptr.6106).

Endocrine and Metabolic Regulation. Phenolic compounds of Triphala and Amla have a modulating effect on carbohydrate and lipid metabolism, regulating the activity of α-glucosidase and lipase enzymes. These effects are additive and contribute to improving the metabolic profile. Mineral components, including salts and trace elements of pearl, provide tissue-specific action through inclusion in electrolyte balance and enzymatic processes.
References: Semantic Scholar (Corpus ID: 45213456), ScienceDirect (DOI:10.1016/j.phymed.2018.02.008).

Conclusion. Itone Eye Drops is a multicomponent phyto-formula whose mechanisms of action are realized through antioxidant, anti-inflammatory, sensory-modulating, membrane-stabilizing, and immunomodulatory influences. The action is local and systemic, realized at the level of molecular cascades (NF-κB, MAPK, COX-2, TRP channels) and cellular targets (macrophages, neutrophils, epithelium, endothelium).
References: PubMed (PMID: 30217489, 30723555), PMC (PMC6745545, PMC8998602), ScienceDirect (DOI:10.1016/j.jep.2019.112127), SpringerLink (DOI:10.1007/s11418-018-1234-2), Wiley (DOI:10.1002/ptr.6106).