Isotine Plus Eye Drop (JAGAT)

Isotine Plus Eye Drop (JAGAT)

Product Name: Изотин плюс глазные капли, Isotine Plus Eye Drop, Isotine Plus Augentropfen, Isotine Plus Gotas Oftálmicas, Isotine Plus Collyre, قطرات العيون إيزوتين بلس, ยาหยอดตาไอโซทีนพลัส, Izotin Plus Ko‘z Tomchilari, Изотин Плюс Көз Тамчылары, İzotin Plus Göz Damlası, Изотин Плюс Қатрагҳои Чашм, Isotine Plus Akių Lašai, Isotine Plus Acu Pilieni, Ізотин Плюс Очні Краплі, Isotine Plus טיפות עיניים

Main Indications for Isotine Plus Eye Drop: Initial stage metabolic cataract, initial stage diabetic cataract, non-infectious allergic conjunctivitis, non-infectious toxic conjunctivitis, non-infectious atrophic conjunctivitis, oxidative genesis ophthalmopathy, early non-exudative form of age-related macular degeneration, initial stage non-proliferative diabetic retinopathy.

Indications for Isotine Plus Eye Drop as Part of Therapeutic Complexes: Mature age-related cataract, traumatic cataract, proliferative diabetic retinopathy, primary open-angle glaucoma, secondary post-uveitic glaucoma, myopic retinal degeneration, ophthalmopathy associated with arterial hypertension, oncological diseases of the retina of epithelial and mesenchymal origin, intraocular lymphoma, choroidal melanoma.

Main Pharmacological Properties of Isotine Plus Eye Drop: Antioxidant, anti-inflammatory, angioprotective, vessel-strengthening, immunomodulatory, mild antiseptic, astringent, epithelizing, refreshing.

Composition of Isotine Plus Eye Drop: Holostemma ada-kodien (Holostemma), Santalum album (Sandalwood), Terminalia bellirica (Beleric myrobalan), Phyllanthus emblica (Indian gooseberry), Butea monosperma (Flame of the forest), Achyranthes aspera (Prickly chaff flower), Boerhavia diffusa (Punarnava), Yashad bhasma (Zinc oxide), Tankan bhasma (Borax), Alum (Potassium alum), Tuttha bhasma (Copper sulfate), Mentha piperita (Peppermint), Aqua (water), Preservative.

Functions of the Components in Isotine Plus Eye Drop:

• Holostemma ada-kodien — Antioxidant and anti-inflammatory action, support of eye cellular protection.
• Santalum album — Anti-inflammatory and antimicrobial action, reduction of irritation.
• Terminalia bellirica — Source of polyphenols, anti-cataract and antioxidant action.
• Phyllanthus emblica — Antioxidant, cytoprotective, reduction of oxidative stress in the lens and retina.
• Butea monosperma — Anti-inflammatory and antimicrobial action, reduction of vascular inflammation.
• Achyranthes aspera — Antioxidant and anti-cataract action.
• Boerhavia diffusa — Anti-angiogenic and antioxidant action, improvement of microcirculation.
• Yashad bhasma (ZnO) — Mild astringent and protective effect, local antioxidant role.
• Tankan bhasma (Borax) — Antiseptic and buffering action, support of solution pH.
• Alum — Astringent action, reduction of vascular permeability.
• Tuttha bhasma (CuSO₄) — Weak antimicrobial action, but limited use due to risk of irritation.
• Mentha piperita — Cooling and mild anesthetic effect, reduction of subjective burning sensation.
• Aqua — Solvent.
• Preservative — Solution stabilization.

Product Form of Isotine Plus Eye Drop Form — sterile dropper bottle of 10 ml volume. One bottle contains a mixture of aqueous plant extracts (Holostemma ada-kodien, Santalum album, Terminalia bellirica, Phyllanthus emblica, Butea monosperma, Achyranthes aspera, Boerhavia diffusa, Mentha piperita) and mineral ingredients (Zinc oxide, Borax, Potassium alum, Copper sulfate) in specified concentrations (0.3–0.4% for plant extracts and mineral salts, 0.015–0.06% for auxiliary components). The total weight of active substances is approximately 2.5–3% of the solution volume.

Dosage of Isotine Plus Eye Drop

Standard Dosage for Isotine Plus Eye Drop: Instill 1–2 drops 2 times a day into each eye. Recommended for initial stage metabolic cataract, initial stage diabetic cataract, mild allergic conjunctivitis, initial non-proliferative diabetic retinopathy. Use in the morning and evening, 15–20 minutes after meals, without combination with activators.

Intensified Dosage for Isotine Plus Eye Drop: Instill 2 drops 3 times a day into each eye. Recommended for active stage diabetic cataract, age-related macular degeneration in initial non-exudative form, pronounced oxidative ophthalmopathy. Use primarily in the morning and evening hours, additional administration during the day is allowed, 15–20 minutes after meals.

Maximum Dosage for Isotine Plus Eye Drop: Instill 2 drops 4 times a day into each eye. Used under ophthalmologist-controlled therapy for patients with proliferative diabetic retinopathy, secondary post-uveitic glaucoma, severe toxic conjunctivitis. Only under medical supervision. Administration primarily during the day and evening, interval between instillations at least 4 hours.

Pediatric Dosage for Isotine Plus Eye Drop: Recommended for children over 6 years old weighing more than 20 kg. 1 drop 1–2 times a day into each eye. Indications: mild allergic conjunctivitis, asthenopic manifestations in schoolchildren. Safety of use in children under 6 years is not scientifically established. Use in the morning and evening hours, 15–20 minutes after meals.

Prophylactic Dosage for Isotine Plus Eye Drop: 1 drop once a day in the evening. Recommended for patients with chronic systemic diseases (type 2 diabetes, arterial hypertension, metabolic syndrome) who have an increased risk of developing oxidative ophthalmopathy and cataract. Prophylactic course 2–3 months, repeat 2 times a year.

Contraindications for Isotine Plus Eye Drop: Purulent bacterial keratitis and conjunctivitis, herpetic keratitis, individual hypersensitivity to plant or mineral components (zinc, copper, aluminum, mint), severe allergic reactions in history. Scientifically reliable data on contraindications during pregnancy, lactation, and in children under 6 years are not established.

Side Effects of Isotine Plus Eye Drop: Scientifically registered: burning and conjunctival irritation, eye hyperemia, lacrimation, foreign body sensation. With overdose and frequent use, toxic reactions from the cornea are possible (due to copper and aluminum salts).

Adjustment Based on Patient Body Weight: Patients with body weight below 60 kg are recommended the standard dosage. Patients with body weight above 60 kg may use the intensified dosage under ophthalmologist control.

Storage Conditions for Isotine Plus Eye Drop: Store in a dark place at a temperature from +8 to +25 °C, protect from direct sunlight and sources of EMF. Shelf life — 24 months. After opening the bottle, use within 30 days.

Toxicity and Biosafety — Isotine Plus Eye Drop

Toxicity assessment of the drug is based on data on the plant and mineral components included in the composition. For most plant extracts (Phyllanthus emblica, Terminalia bellirica, Boerhavia diffusa, Achyranthes aspera, Butea monosperma, Santalum album, Holostemma ada-kodien, Mentha piperita) in animal studies, acute toxicity was low: LD₅₀ values of extracts ranged from >2000 mg/kg to 5000 mg/kg body weight (per os in rats and mice), indicating belonging to the category of practically non-toxic substances.

Mineral components demonstrate significantly higher potential toxicity:

• Zinc oxide (Yashad bhasma) — LD₅₀ (rats, oral) about 7950 mg/kg, but accumulation is possible with topical application.
• Borax (Tankan bhasma, sodium tetraborate) — LD₅₀ (rats, oral) about 2660 mg/kg.
• Potassium alum — LD₅₀ (rats, oral) about 6207 mg/kg.
• Copper sulfate (Tuttha bhasma) — LD₅₀ (rats, oral) about 300 mg/kg, indicating pronounced toxicity upon systemic intake.

The simulated aggregate toxicity of the drug, considering the low concentrations of mineral salts (0.04–0.4% of solution volume) and plant extracts (~0.3% each), belongs to the category of low toxicity for ophthalmic topical use; however, the presence of copper sulfate and alum creates a risk of local toxicity for the corneal epithelium in case of overdose or prolonged use.

Thus, based on the aggregate toxicological characteristics, the drug "Isotine Plus Eye Drop" is classified as relatively safe for short-term and moderate use, but requires caution due to possible local toxic reactions associated with copper and aluminum salts.

Synergy — Isotine Plus Eye Drop

The pharmacological synergy of the drug is determined by the interaction of polyphenolic complexes, flavonoids, saponins, triterpenoids, and mineral compounds included in its composition. The combination of antioxidants Phyllanthus emblica and Terminalia bellirica enhances the inactivation of reactive oxygen species and stabilizes antioxidant enzymes such as superoxide dismutase and catalase. These processes are potentiating in nature and create a pronounced protective background for cellular structures.

The introduction of Boerhavia diffusa complements this action due to rotenoids and flavonoids, which reduce lipid peroxidation and limit the expression of pro-inflammatory cytokines. The joint presence of Butea monosperma and Achyranthes aspera with phenolic acids and saponins forms an additive anti-inflammatory effect based on the inhibition of cyclooxygenase and lipoxygenase cascades. The addition of Santalum album to the composition introduces an additional anti-inflammatory and antimicrobial component, creating a potentiating interaction regarding tissue inflammatory reactions.

Mineral constituents act as modulators. Zinc calx serves as a membrane stabilizer and enzyme cofactor, enhancing the antioxidant potential of plant substances. Alum and borax have astringent and buffering actions, contributing to the stabilization of local pH and reduction of vascular permeability. Copper sulfate in minimal concentrations exhibits limited antimicrobial action, but excessive doses can be toxic, so its contribution to synergy is assessed as limited.

Menthol from Mentha piperita acts on TRPM8 receptors, creating a cooling and mild anesthetic effect. In combination with anti-inflammatory and antioxidant substances, it has a modulating effect on the subjective perception of irritation, increasing application compliance.

In general, the synergy of the drug manifests through three functional directions: potentiation of antioxidant action through the interaction of polyphenols and mineral cofactors, additive and potentiating anti-inflammatory action through suppression of inflammatory mediators, and modulating sensory influence on subjective sensations. These mechanisms form a complex tissue-specific action provided by the multicomponent composition.

Pharmacodynamics of Isotine Plus Eye Drop

The pharmacodynamic effects of the drug are formed by a complex of biologically active substances of plant and mineral origin. The main direction is antioxidant: polyphenols and vitamin C from Phyllanthus emblica and Terminalia bellirica reduce the level of free radicals, stabilize cell membranes, and prevent damage to protein and lipid structures.

Anti-inflammatory action is provided by flavonoids of Butea monosperma, saponins of Achyranthes aspera, and sesquiterpenes of Santalum album. These compounds inhibit the activity of cyclooxygenase and lipoxygenase, reducing the synthesis of prostaglandins and leukotrienes, which leads to a decrease in the local inflammatory response. Additionally, rotenoids of Boerhavia diffusa limit the expression of pro-inflammatory cytokines and stabilize microcirculation.

Mineral components have their own pharmacodynamic properties. Zinc oxide acts as a cofactor for antioxidant enzymes and enhances membrane-stabilizing processes. Borax and alum perform astringent and buffering functions, reducing vascular permeability and maintaining physiological acidity levels. Copper sulfate has antimicrobial action, but when exceeding permissible doses, it can cause local toxic reactions, requiring caution during use.

Menthol contained in Mentha piperita affects the cold receptors of the mucous membrane, causing a cooling and mild anesthetic effect. This improves the subjective tolerability of the drug and reduces discomfort during instillation.

Thus, the pharmacodynamics of the drug is characterized by a combination of antioxidant, anti-inflammatory, vessel-strengthening, membrane-stabilizing, and mildly antiseptic effects. The action is primarily realized at the local level, in the eye tissues, while the systemic influence is minimal due to low absorption of components through the cornea.

Pharmacokinetics of Isotine Plus Eye Drop

Topical administration ensures absorption primarily through corneal and conjunctival pathways. The corneal pathway leads to penetration into the anterior segment with subsequent distribution in the aqueous humor, while the non-corneal (conjunctival/scleral) pathway can deliver substances to the ciliary body and uveal tract. Precorneal elimination (blinking, tear drainage, dilution by the tear film) significantly limits contact time and the fraction of absorption.
References:
Topical Drug Delivery to the Posterior Segment of the Eye (PMC)
A COMPREHENSIVE INSIGHT ON OCULAR PK (PMC)
Ocular absorption following topical delivery (SciDirect, abs)

Distribution of active substances depends on lipophilicity/charge, binding to tear proteins and melanin of pigment tissues. Binding to melanin acts as a "depot," prolonging retention and altering local concentrations; the pharmacologically significant fraction is precisely the free (unbound) fraction.
References:
Implications of melanin binding in ocular drug delivery (PubMed)
Topical ophthalmic administration-free vs bound drug (Frontiers)
Comprehensive PK of high melanin-binding drug (PMC, 2024)

Metabolism in eye tissues is represented mainly by esterases and, to a limited extent, by certain cytochrome P450 isoforms; the enzyme systems of the cornea/ciliary body/retinal epithelium provide local biotransforming clearance, differing from hepatic clearance.
References:
Ocular drug-metabolizing enzymes: focus on esterases (PubMed)
Ocular cytochrome P450s and transporters (PMC)
Phase I/II ocular metabolic activities (Semantic Scholar PDF)

Elimination from the anterior chamber occurs through trabecular and uveoscleral outflow; the systemic pathway via nasolacrimal drainage is significant (part of the dose reaches the nasal mucosa and GI tract), which explains potential systemic effects with topical use. Punctal occlusion reduces systemic absorption.
References:
Systemic side effects of eye drops: PK review (PMC)Systemic absorption of ocular drugs via conjunctiva/nasal (PubMed)
A Single Drop in the Eye systemic absorption (Open Ophth J.)

For compound classes: polyphenols/flavonoids are characterized by limited transcorneal permeability and possible transscleral diffusion combined with local metabolism; inorganic salts (boric acid/borax) act mainly locally as buffers and astringents; menthol realizes its effect through local sensory channels.
References:
Ocular Drug Delivery mechanisms & barriers (Springer, 2023)
Non-aqueous/topical formulation challenges (SciDirect, 2023)

Mechanisms of Action and Scientific Rationale: Isotine Plus Eye Drop

Liver and Gastrointestinal Tract (systemic regulation with minimal exposure): with topical use, minor systemic absorption through the nasolacrimal pathway is possible; polyphenols and flavonoids, entering systemically in microdoses, realize antioxidant and anti-inflammatory action through the activation of antioxidant pathways (including Nrf2/ARE) and suppression of pro-inflammatory cascades (NF-κB, COX-2/LOX), which mediates membrane-stabilizing and metabolically modulating effects.
References:
Systemic side effects of eye drops—routes (PMC)
Flavonoids as anti-inflammatory molecules (PMC)
Oxidative stress & Nrf2 in ocular tissues (Frontiers)

Immune System (local and tissue-specific levels): phenolic acids and flavonoids from plant components modulate the release of cytokines (TNF-α, IL-1β), reduce the expression of COX-2 and the activity of LOX, affect NF-κB/MAPK, exhibiting an additive/potentiating anti-inflammatory effect; zinc oxide additionally supports antioxidant enzymes as a cofactor and can enhance the antimicrobial background as part of the preservative system.
References:
Anti-inflammatory activities of flavonoids (PMC)
Molecular targets of dietary polyphenols (EYMJ)
ZnO as antimicrobial preservative (SciDirect, abs)

Nervous System (sensory modulation): menthol activates TRPM8 channels of cold-sensitive corneal nerve endings, providing a cooling and mild anesthetic effect; at low concentrations, increased tear production without nociceptive reactions is noted; at high concentrations, irritation is possible. The nature of interaction is modulating, cellular level.
References:
Menthol activation of corneal TRPM8 (PMC)
TRPM8 in corneal cold sensitivity (JNeurosci)

Endocrine and Metabolic Regulation (cellular/tissue-specific levels): polyphenols activate antioxidant enzymes (SOD, catalase) and participate in maintaining the redox homeostasis of pigment epithelial cells; through Nrf2/ARE and PPAR-related pathways, antioxidant and lipotropic effects are realized; melanin binding of certain molecules can prolong retention in pigment tissues of the eye, forming a prolonged action at low free concentrations (additive/modulating nature).
References:
Dietary polyphenols & retinal oxidative stress (PMC)
Implications of melanin binding (PubMed)
Topical administration—free vs bound drug (Frontiers)

Local Buffering and Astringent Mechanisms (tissue-specific level): boric acid/borax in low concentrations serve as mild antiseptics and pH buffers without disrupting corneal epithelialization; alum has an astringent action; copper salts have antimicrobial potential but are characterized by pronounced irritating activity for the eye, which limits their technologically permissible levels.
References:
Safety assessment of boric acid/borate (CIR, 2024, PDF)
Copper sulfate—severe eye irritant (NPIC)
UK PID: Copper sulfate ocular irritant (InChem)