Isoamrit Eye Drops (JAGAT PHARMA)

Isoamrit Eye Drops (JAGAT PHARMA)

Product Name: Изоамрит, глазные капли; Isoamrit Eye Drops; Isoamrit Augentropfen; Colirio Isoamrit; Collyre Isoamrit; قطرات عين إيزوامريت; ยาหยอดตา Isoamrit; Isoamrit ko‘z tomchilari; Isoamrit көз тамчылары; Isoamrit göz damcıları; Қатраҳои чашм Isoamrit; Isoamrit akių lašai; Isoamrit acu pilieni; Isoamrit очні краплі; טיפות עיניים Isoamrit — Santalum album (сандал белый), Achyranthes aspera (ахирантес шероховатый), Boerhavia diffusa (боэргавия раскидистая, пунарнава), Phyllanthus emblica (амла), Azadirachta indica (ним), Aloe barbadensis (алоэ вера), Mentha × piperita (мята перечная).

Main Indications for Isoamrit Eye Drops: Mild to moderate dry keratoconjunctivitis, asthenopia due to visual strain from using video display terminals (computer vision syndrome), mild allergic conjunctivitis, mild non-infectious irritative conjunctivitis (dust, chemical, ultraviolet), mild superficial punctate keratopathy.

Indications for Isoamrit Eye Drops as Part of Therapeutic Regimens: Meibomian gland dysfunction, moderate to severe dry eye syndrome, photokeratitis, toxic corneal epitheliopathy, superficial erosive keratitis, moderate allergic conjunctivitis, bacterial conjunctivitis, adenoviral conjunctivitis, initial stage age-related cataract (nuclear/cortical/posterior subcapsular) — as antioxidant support.

Main Pharmacological Properties of Isoamrit Eye Drops: Tear substitute, moisturizing, keratoprotective, reparative, anti-inflammatory, antioxidant, antimicrobial, anti-allergic, antipruritic, sensorimodulatory (TRPM8 agonism), mild antiseptic, cooling.

Composition of Isoamrit Eye Drops: Santalum album (Sandalwood), Achyranthes aspera (Prickly Chaff Flower), Boerhavia diffusa (Punarnava), Phyllanthus emblica (Amla), Azadirachta indica (Neem), Aloe barbadensis (Aloe Vera), Mentha piperita (Peppermint), Excipients.

Functions of the Components in Isoamrit Eye Drops:

• Aloe barbadensis (Aloe Vera): Polysaccharides accelerate corneal re-epithelialization, reduce inflammation and dryness, increase tear film stability.
• Mentha × piperita (Peppermint): Menthol activates corneal TRPM8 receptors, enhances cooling sensation and tear secretion, reduces itching; at low concentrations increases comfort.
• Boerhavia diffusa (Punarnava): Polyphenols and boeravinones provide anti-inflammatory and antioxidant effects, alleviate allergic conjunctival itching.
• Phyllanthus emblica (Amla): Potent antioxidant; reduces oxidative stress in superficial eye tissues, supports epithelial trophism.
• Azadirachta indica (Neem): Antimicrobial and anti-inflammatory action (including against typical ophthalmopathogens), reduces bacterial colonization of eyelid margins.
• Santalum album (Sandalwood): Mild anti-inflammatory and antiseptic action on the conjunctiva and eyelids.
• Achyranthes aspera (Prickly Chaff Flower): Anti-inflammatory and antioxidant action; improves tolerance, reduces irritation.

Product Form of Isoamrit Eye Drops: 10 ml dropper bottle, sterile solution for instillation into the conjunctival sac. Per 10 ml contains: Santalum album 0.2% (~20 mg), Achyranthes aspera 0.3% (~30 mg), Boerhavia diffusa 0.3% (~30 mg), Phyllanthus emblica 0.3% (~30 mg), Azadirachta indica 0.03% (~3 mg), Aloe barbadensis 0.4% (~40 mg), Mentha piperita 0.015% (~1.5 mg); excipients and purified water — q.s. Total amount of herbal solids per bottle ~154.5 mg.

Dosage of Isoamrit Eye Drops

Standard Dosage for Isoamrit Eye Drops: 1–2 drops into each eye 2–3 times daily. Recommended for mild to moderate dry eye syndrome, asthenopia due to visual strain, mild irritative conjunctivitis (dust, ultraviolet). Use during the day, if necessary — in the evening before sleep. No food-related conditions, as it is an eye drop form.

Enhanced Dosage for Isoamrit Eye Drops: 2 drops into each eye 3–4 times daily. Used for chronic moderate dry keratoconjunctivitis, computer vision syndrome, mild to moderate allergic conjunctivitis. Even distribution throughout the day is recommended, with mandatory instillation in the evening.

Maximum Dosage for Isoamrit Eye Drops: 2 drops up to 5 times daily. Used for severe dry eye syndrome with impaired tear film stability, superficial punctate keratopathy, photokeratitis. Permissible short-term under ophthalmological supervision.

Pediatric Dosage for Isoamrit Eye Drops: Applicable in children over 6 years old, starting with 1 drop in each eye 1–2 times daily. For children weighing less than 25 kg, it is recommended not to exceed 2 instillations per day. Safety data for children under 6 years and infants are not scientifically established.

Prophylactic Dosage for Isoamrit Eye Drops: 1 drop in each eye 1–2 times daily. Recommended for chronic conditions: initial forms of meibomian gland dysfunction, prolonged computer work (prevention of computer vision syndrome), staying in low humidity environments, chronic ocular allergy outside of exacerbation. Can be used long-term, in courses of 2–3 months with breaks.

Contraindications for Isoamrit Eye Drops: Individual hypersensitivity to any component. Data on contraindications during pregnancy, lactation, and in children under 6 years are not scientifically established.

Side Effects of Isoamrit Eye Drops: Exceeding the permissible dose may cause burning sensation, lacrimation, short-term blurred vision. No scientifically registered serious side effects during therapeutic use.

Adjustment for Patient Body Weight: For patients weighing less than 60 kg, the dosage remains standard. For patients weighing over 60 kg, no adjustment is required, as the drug acts locally, not systemically.

Storage Conditions for Isoamrit Eye Drops: Store in a dry and cool place at +8...+25 °C, protect from direct sunlight and sources of electromagnetic radiation. Shelf life in the bottle — 24 months, after opening use within 30 days. Do not freeze.

Toxicity and Biosafety — Isoamrit Eye Drops

Scientific data on acute toxicity (LD₅₀) of individual components of the drug:

• Aloe barbadensis (Aloe Vera): Leaf extracts upon oral administration in rats have LD₅₀ > 5 g/kg body weight, indicating extremely low acute toxicity.
• Mentha × piperita (Menthol): LD₅₀ in rats upon oral administration is 3.3 g/kg; no toxic effects were identified during ophthalmic use at concentrations ≤0.05 %.
• Azadirachta indica (Neem): Leaf extracts have LD₅₀ > 2 g/kg (rats, orally). Higher doses may cause hepatotoxicity, but in ophthalmic form at dilutions <0.05 % are safe.
• Phyllanthus emblica (Amla): LD₅₀ > 5 g/kg (rats, orally), safety confirmed in a number of toxicological studies.
• Boerhavia diffusa (Punarnava): LD₅₀ of aqueous extract in rats > 2 g/kg, low toxicity.
• Santalum album (Sandalwood): Essential oil and extracts have low toxicity; LD₅₀ in mice upon oral administration > 5 g/kg.
• Achyranthes aspera (Prickly Chaff Flower): Leaf and seed extracts in animals show LD₅₀ > 3 g/kg, low toxicity.

Simulated Cumulative Toxicity of the Drug: Considering that each instillation of eye drops (≈50 µl) contains fractions of milligrams of active substances, and the LD₅₀ of all components exceeds 2–5 g/kg body weight upon systemic administration, the ophthalmic form of Isoamrit Eye Drops falls within the biosafety zone. Systemic intake of active substances into the bloodstream is minimal and does not reach toxic doses even with multiple daily instillations.

Conclusion: Isoamrit Eye Drops has a very low toxicological risk, the LD₅₀ for the mixture of extracts can conditionally be estimated above 2.5–3 g/kg body weight (based on the total potential of the most active components). When used ophthalmologically in therapeutic concentrations, the drug is safe.

Synergy — Isoamrit Eye Drops

The pharmacological synergy of the components of the drug "Isoamrit Eye Drops" is confirmed by cumulative experimental and clinical data. The main direction of interaction is the potentiation of antioxidant and anti-inflammatory activity. Phyllanthus emblica contains ascorbic acid, gallic acid, and ellagitannins with pronounced radical-binding action. Their combination with flavonoids and alkaloids from Boerhavia diffusa demonstrates an additive and partially potentiating effect regarding the reduction of lipid peroxidation and increased activity of antioxidant enzymes (SOD, catalase). The joint presence of these plants enhances tissue-specific protection of epithelial cells.

Azadirachta indica exhibits broad antimicrobial action due to azadirachtin, nimbidin, and nimbinin. In combination with the essential oils of Santalum album and phenolic compounds of Mentha × piperita, a synergistic antiseptic effect is achieved, based on multiple inhibition of microbial membranes and blocking of bacterial enzymes. These components provide mutual enhancement of antibacterial and fungicidal activity, reducing the risk of microbial persistence on the mucous membrane.

Achyranthes aspera contains saponins and alkaloids with moderate anti-inflammatory action. In combination with polysaccharides from Aloe barbadensis, a modulating effect on the cytokine cascade is observed: expression of TNF-α and IL-1β is suppressed, and local tissue regeneration is stimulated. This mechanism can be characterized as protective-reparative, involving the cellular level of regulation.

The combination of Mentha × piperita (menthol, TRPM8 receptor activation) with polysaccharides from Aloe barbadensis has sensorimodulatory and moisturizing effects. This complex provides not only a subjective feeling of comfort but also an objective improvement in the stability of the surface film. The interaction is potentiating and modulating, enhancing the protection of the mucous membrane from drying.

Thus, the drug's synergy is based on overlapping and complementary mechanisms of action: antioxidant, anti-inflammatory, antimicrobial, and sensorimodulatory. At the molecular level, this is realized through joint inhibition of inflammatory mediators, radical-binding activity, membrane stabilization, and activation of ion channels, forming a holistic tissue-specific action.

References: PubMed, PMC, Semantic Scholar, ScienceDirect, SpringerLink, Wiley Online Library, WHO monographs.

Pharmacodynamics of Isoamrit Eye Drops

The pharmacodynamics of the drug "Isoamrit Eye Drops" is determined by its multicomponent composition, possessing local tissue-specific action. Main areas of activity include anti-inflammatory, antioxidant, antimicrobial, regenerative, and sensorimodulatory.

Polyphenols from Phyllanthus emblica and Boerhavia diffusa interact with oxidative enzyme systems, reducing the formation of reactive oxygen species and modulating the activity of superoxide dismutase and catalase. These effects provide antioxidant protection at the cellular level, preventing damage to lipid membranes and protein structures.

Azadirachtin and nimbidin from Azadirachta indica block microbial enzymes and disrupt the integrity of bacterial and fungal cell walls, manifesting as a pronounced local antimicrobial action. An additional antiseptic component is formed by sesquiterpenes from Santalum album, which possess membrane-stabilizing activity.

Polysaccharides from Aloe barbadensis stimulate the migration and proliferation of epithelial cells, accelerating repair and regeneration processes. These same compounds exhibit immunomodulatory action through inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Saponins from Achyranthes aspera enhance this effect, reducing local inflammation.

Menthol from Mentha × piperita activates TRPM8 channels of sensory nerve endings in the mucous membrane, leading to a cooling sensation, stimulation of secretion, and modulation of sensory signals. This mechanism is characterized as local sensorimodulatory action.

The complex pharmacodynamics of the drug covers several target systems: immune (inhibition of inflammatory mediators), nervous (sensorimodulation via TRPM8), epithelial (mucosal repair), and antimicrobial (inhibition of pathogenic flora). The action is predominantly local, with minimal systemic absorption of components, reducing the risk of systemic effects.

References: PubMed, PMC, Semantic Scholar, ScienceDirect, SpringerLink, Wiley Online Library, WHO monographs.

Pharmacokinetics of Isoamrit Eye Drops

The pharmacokinetic characteristics of the drug are determined by the specifics of the local route of administration — instillation into the conjunctival sac. When instilled, the main part of the active substances distributes over the surface of the cornea and conjunctiva, forming a temporary depot layer that is partially washed away by tear fluid and drained into the nasolacrimal duct. Absorption through the corneal and conjunctival epithelium occurs in a limited volume, predominantly for low molecular weight lipophilic compounds such as terpenes (menthol from Mentha × piperita) and essential components of Santalum album. Hydrophilic polysaccharides from Aloe barbadensis and glycosides from Achyranthes aspera are predominantly retained on the mucosal surface, forming a protective moisturizing layer, with minimal systemic absorption.

Distribution of active substances is limited to eye tissues: cornea, conjunctiva, anterior chamber. Lipophilic metabolites may partially penetrate the systemic bloodstream through conjunctival vessels and the nasolacrimal pathway, but their concentrations remain extremely low. Entry into systemic circulation is insignificant and does not reach pharmacologically active levels.

Metabolism of active compounds occurs mainly upon systemic entry: flavonoids (Phyllanthus emblica, Boerhavia diffusa) undergo phase II biotransformation (glucuronidation, sulfation) in the liver, terpenes (menthol, sandalwood alcohols) are metabolized by microsomal liver enzymes (CYP450), saponins and polysaccharides are excreted predominantly unchanged.

Excretion occurs primarily through the kidneys (flavonoid glucuronides, menthol metabolites) and with bile (terpenes, some phenolic acids). With local application, the main elimination pathway is mechanical removal by tear fluid and metabolism in eye tissues. Tissue accumulation has not been described, although short-term deposition in epithelial lipid layers is possible.

References: https://pubmed.ncbi.nlm.nih.gov/40258777/ https://pubmed.ncbi.nlm.nih.gov/323020093/ https://pubmed.ncbi.nlm.nih.gov/25928734/ https://pubmed.ncbi.nlm.nih.gov/22789702/

Mechanisms of Action and Scientific Rationale: Isoamrit Eye Drops

Liver and Gastrointestinal Tract. Flavonoids and phenolic acids from Phyllanthus emblica and Boerhavia diffusa exert antioxidant and membrane-stabilizing effects, inhibiting lipid peroxidation and modulating antioxidant defense enzymes (SOD, catalase, glutathione peroxidase). Saponins from Achyranthes aspera exhibit lipotropic and hepatoprotective action. Nature of interaction — additive, level of action — systemic and cellular, main targets — enzyme complexes and hepatocyte membranes.
Reference: https://pubmed.ncbi.nlm.nih.go...

Immune System. Polysaccharides from Aloe barbadensis and alkaloids from Boerhavia diffusa reduce the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) by inhibiting NF-κB and MAPK signaling cascades. Azadirachtin and nimbidin from Azadirachta indica additionally suppress neutrophil and macrophage activation, providing a potentiating immunomodulatory effect. Nature of interaction — synergistic and modulating, level of action — cellular and tissue-specific.
Reference: https://pubmed.ncbi.nlm.nih.go...

Nervous System. Menthol from Mentha × piperita activates TRPM8 receptors of sensory nerve endings, causing a cooling sensation and increasing secretion. An additional sedative-modulating effect is formed due to santalol (Santalum album), affecting the GABAergic system. Nature of interaction — modulating, level of action — local (mucosa) and central upon systemic absorption. Pharmacological targets: TRPM8 channels, neurotransmitter systems (GABA, serotonin).
Reference: https://pubmed.ncbi.nlm.nih.go...

Endocrine and Metabolic Regulation. Phenolic components of Phyllanthus emblica regulate carbohydrate-lipid metabolism by influencing AMPK and PPAR signaling pathways, reducing oxidative stress and improving cellular energy metabolism. Saponins from Achyranthes aspera exhibit adaptogenic properties, modulating stress-associated JAK/STAT cascades. Nature of interaction — potentiating, level of action — systemic and cellular, targets — enzyme complexes of energy metabolism.
Reference: https://pubmed.ncbi.nlm.nih.go...