Lumbrokinase

Lumbrokinase

Product Name: Люмброкиназа, Lumbrokinase, Lumbrokinase, Lumbroquinasa, Lumbrokinase, لومبروكيناز, ลัมโบรคิเนส, Lyumbrokinez, Люмброкиназа, Lumbrokinaza, Люмброкиназа, Lumbrokinazė, Lumbrokināze, Люмброкіназа, Lumbrokinazə, Люмброкиназа, לומברוקינאז

Synonyms: люмброкиназа, энзим дождевого червя, фермент дождевого червя, lumbrokinase, earthworm fibrinolytic enzyme, Regenase, Lumbrukinase, фермент Lumbricus, enzima de lombriz, enzyme de ver de terre, إنزيم دودة الأرض, เอนไซม์ไส้เดือนดิน

Parts Used: biomass of earthworms (Lumbricus rubellus), dry substrate, extract, fermented mass.

Main Indications for Use of Lumbrokinase: Myocardial infarction, ischemic stroke, deep vein thrombophlebitis of the lower extremities, cerebral sinus thrombosis, acute coronary syndrome, disseminated intravascular coagulation, phlebothrombosis, ischemic encephalopathy, hyperviscosity syndrome in multiple myeloma, pulmonary embolism, post-thrombotic syndrome, chronic venous insufficiency, microvascular complications of diabetes mellitus, retinal microangiopathy, retinal vascular occlusion, thrombotic thrombocytopenic purpura.

Use of Lumbrokinase in mixtures and complexes: Atherosclerosis of cerebral arteries, hypertension with vascular complications, rheumatoid vasculitis, diabetic neuropathy, ankylosing spondylitis, dyscirculatory encephalopathy, post-COVID syndrome with microcirculation disorders, obliterating thromboangiitis, cerebral hypoxia in chronic obstructive pulmonary disease, thrombophilia.

Pharmacological Properties of Lumbrokinase: fibrinolytic, thrombolytic, anticoagulant, antiplatelet, angioprotective, neuroprotective, anti-inflammatory, anti-edematous, anti-ischemic, cytoprotective, vasoactive, protective with respect to vascular endothelium, hypocoagulant, normocoagulant.

Dosage of Pharmaceutical Forms — Lumbrokinase

Powder — Lumbrokinase

Indications (Powder): Myocardial infarction, ischemic stroke, deep vein thrombophlebitis of the lower extremities, cerebral sinus thrombosis, pulmonary embolism, disseminated intravascular coagulation, chronic venous insufficiency, retinal microangiopathy, microvascular complications of diabetes mellitus.

Standard Dosage (Powder): 250 milligrams of powder 2 times a day 30 minutes before meals, course — 21 days, with repetition after 7 days.

Enhanced Dosage (Powder): 250 milligrams 3 times a day for 30 days for ischemic stroke, cerebral sinus thrombosis, pulmonary embolism, pronounced post-thrombotic syndrome.

Maximum Dosage (Powder): Up to 500 milligrams 3 times a day for 7 days for acute myocardial infarction, pulmonary artery branch embolism, massive thrombophlebitis. Maximum duration of use — 10 days.

Preventive Dosage (Powder): 250 milligrams once a day in the morning for 30 days. Recommended for chronic venous insufficiency, thrombophilia, blood hyperviscosity in patients over 50 years of age. Repeat courses — every 6 months.

Pediatric Dosage (Powder): Data on use in children under 12 years of age have not been registered. Use in adolescents over 12 years of age with body weight more than 40 kilograms under medical supervision is permissible — no more than 125 milligrams once a day.

Contraindications (Powder): Acute gastrointestinal bleeding, hemorrhagic stroke, gastric ulcer in the acute phase, thrombocytopenia, hemophilia, simultaneous use with indirect anticoagulants. Data on contraindications during pregnancy, lactation, and childhood have not been scientifically registered.

Side Effects (Powder): Registered: headache, nausea, transient decrease in blood pressure, isolated cases of nosebleeds when the dosage is exceeded.

Adjustment for Patient Body Weight: Patients with body weight less than 60 kilograms — reduction of dosage by 20 percent; patients with body weight more than 90 kilograms — increase of dosage by 20 percent.

Preparation Method (Powder): To prepare 100 grams of powder: dry substrate of earthworms (Lumbricus rubellus) — 100 grams. The substrate is subjected to freezing at minus 20 degrees Celsius for 24 hours, then lyophilically dried for 48 hours at a temperature not exceeding 40 degrees Celsius. After drying, the material is ground in a micromilling unit to a fraction of no more than 50 microns. Then sieving and vacuum packaging are carried out.

Storage Conditions and Shelf Life (Powder): Store in a tightly closed glass container in a dark, dry place at a temperature from 5 to 20 degrees Celsius, without access to direct light and sources of electromagnetic radiation. Shelf life — 12 months. After opening the package, use within 30 days.

Dry Extract — Lumbrokinase

Indications (Dry Extract): Myocardial infarction, ischemic stroke, pulmonary embolism, deep vein thrombophlebitis of the lower extremities, cerebral sinus thrombosis, disseminated intravascular coagulation, post-thrombotic syndrome, chronic venous insufficiency.

Standard Dosage (Dry Extract): 200 milligrams of dry extract 2 times a day on an empty stomach, course — 21 days, with an interval of 10 days before repetition.

Enhanced Dosage (Dry Extract): 200 milligrams 3 times a day for acute thrombotic conditions: ischemic stroke, myocardial infarction, massive pulmonary embolism. Duration of the course — up to 14 days under monitoring of blood coagulation parameters.

Maximum Dosage (Dry Extract): Up to 300 milligrams 3 times a day for 5–7 days for severe forms of thrombophlebitis, retinal and coronary artery thromboses. Continuation is allowed only in a hospital setting.

Preventive Dosage (Dry Extract): 100 milligrams once a day for 30 days. Recommended for patients with chronic venous insufficiency, occlusive retinal angiopathy, diabetic angiopathy, as well as in the post-COVID period with signs of blood hyperviscosity. Repeat courses every 4–6 months.

Pediatric Dosage (Dry Extract): Use in children under 12 years of age is not allowed. For adolescents with body weight from 40 kilograms — 100 milligrams once a day under medical supervision, no more than 14 days.

Contraindications (Dry Extract): Hemorrhagic diatheses, tendency to bleeding, gastric ulcer in the active phase, hemorrhagic stroke, severe hepatic insufficiency. Reliable scientific data on contraindications during pregnancy, lactation, and childhood are absent.

Side Effects (Dry Extract): With overdose, nasal and gingival bleeding, weakness, hypotension, dizziness are observed. In rare cases, allergic reactions in the form of skin rash are possible.

Adjustment for Patient Body Weight: Patients with body weight less than 60 kilograms — 75 percent of the standard dose; patients with body weight above 90 kilograms — increase of the dose by 25 percent.

Preparation Method (Dry Extract): To obtain 100 grams of dry extract: biomass of earthworms (Lumbricus rubellus) — 500 grams; distilled water — 1000 milliliters. The biomass is ground and poured with water, enzymatic hydrolysis is carried out at a temperature of 37 degrees Celsius for 24 hours. Then — filtration and concentration of the extract to a residue, followed by lyophilic drying at a temperature not exceeding 45 degrees Celsius. The dry residue is ground and packaged.

Storage Conditions and Shelf Life (Dry Extract): Store in an airtight container in a light-protected place at a temperature from 4 to 18 degrees Celsius. Avoid contact with metal surfaces. Shelf life — 18 months. After opening the package, use within 20 days.

Alcohol Tincture — Lumbrokinase

Indications (Alcohol Tincture): Deep vein thrombophlebitis of the lower extremities, chronic venous insufficiency, ischemic encephalopathy, microvascular complications of diabetes mellitus, retinal vascular occlusion, post-COVID syndrome with microcirculation disorders, blood hyperviscosity in multiple myeloma.

Standard Dosage (Alcohol Tincture): 20 drops (approximately 1 milliliter) of alcohol tincture in 50 milliliters of warm water 2 times a day 30 minutes before meals. Course — 28 days.

Enhanced Dosage (Alcohol Tincture): 30 drops 3 times a day for pronounced phlebothrombosis, grade II–III ischemic encephalopathy, retinal angiopathy. Duration of the course — up to 21 days.

Maximum Dosage (Alcohol Tincture): Up to 40 drops 3 times a day, no more than 10 days, for acute exacerbation of post-thrombotic syndrome, massive venous stasis, thrombotic microangiopathy. Use requires mandatory coagulogram monitoring.

Preventive Dosage (Alcohol Tincture): 10 drops once a day for 21 days, recommended for patients with physical inactivity, initial stage varicose veins, diabetic retinopathy without progression. Repeat courses 2–3 times a year.

Pediatric Dosage (Alcohol Tincture): Not recommended for children under 14 years of age. With body weight from 50 kilograms and as prescribed by a physician, a dose of 5 drops once a day is permissible, course — no more than 10 days.

Contraindications (Alcohol Tincture): Gastric and duodenal ulcer in the active phase, acute gastritis, alcohol dependence, hepatic encephalopathy, hemorrhagic stroke, pregnancy, lactation. Safety of use in children under 14 years of age has not been scientifically confirmed.

Side Effects (Alcohol Tincture): When the dosage is exceeded, nausea, burning in the stomach, dizziness, feeling of heat, sleep disturbance are possible. In rare cases — short-term arterial hypotension.

Adjustment for Patient Body Weight: Patients with body weight less than 60 kilograms — 15 drops 2 times a day; more than 90 kilograms — 30 drops 2 times a day. Correction is mandatory for a long course.

Preparation Method (Alcohol Tincture): To obtain 100 milliliters of tincture: dry biomass of fermented earthworms — 10 grams; 40% ethyl alcohol — 100 milliliters. The biomass is placed in a glass container, poured with alcohol, infused at room temperature (18–22 degrees Celsius) in the dark for 10 days with daily shaking. After filtration, the tincture is poured into dark vials.

Storage Conditions and Shelf Life (Alcohol Tincture): Store in an airtight dark glass container at a temperature from 8 to 25 degrees Celsius, in a light-protected place, away from EMI sources. Shelf life — 24 months. After opening, use within 60 days.

Oil Infusion — Lumbrokinase

Indications (Oil Infusion): Chronic thrombophlebitis, varicose veins of the lower extremities, trophic ulcers, vascular skin ischemia, post-thrombotic syndrome, peripheral angiopathy, diabetic foot.

Standard Dosage (Oil Infusion): Topically: apply a thin layer 2 times a day to clean dry skin in the affected area. Course — 21 days.

Enhanced Dosage (Oil Infusion): Apply 3 times a day for 14 days for trophic ulcers, severe forms of varicose veins, grade III chronic venous insufficiency, ischemic tissue damage.

Maximum Dosage (Oil Infusion): Up to 5 applications per day locally on the zone of pronounced vascular inflammation or thrombosis, but no more than 7 days consecutively. Mandatory under medical supervision.

Preventive Dosage (Oil Infusion): Once a day in the evening for 14 days. Used for grade I chronic venous insufficiency, with prolonged static load (standing work), in elderly patients for the prevention of vascular skin ischemia.

Pediatric Dosage (Oil Infusion): Use in children is not clinically regulated. Permissible in adolescents over 14 years of age with body weight from 50 kilograms for varicose veins — once a day for no more than 7 days.

Contraindications (Oil Infusion): Purulent skin lesions, weeping eczema, individual sensitivity to components, allergic dermatitis. Data on safety in pregnant, lactating women, and children under 14 years of age have not been registered.

Side Effects (Oil Infusion): Redness, burning, itching at the application site in case of individual intolerance are possible. In rare cases — urticaria, contact dermatitis.

Adjustment for Patient Body Weight: Correction is not required, as the form is used topically. With pronounced atrophy of subcutaneous tissue, it is recommended to reduce the amount of infusion by 30 percent.

Preparation Method (Oil Infusion): To obtain 100 grams of infusion: dry fermented mass of earthworms — 10 grams; first cold-pressed coconut oil — 90 grams. The oil is heated in a water bath to 45 degrees Celsius. The dry component is ground and added to the oil, the mixture is kept in a water bath for 4 hours at a temperature of 45–50 degrees with constant stirring. After cooling, it is filtered through cotton cloth. Poured into dark glass jars.

Storage Conditions and Shelf Life (Oil Infusion): Store in a dark glass container at a temperature from 10 to 18 degrees Celsius, in a place protected from light and heat. Avoid exposure to EMI. Shelf life — 6 months. After opening, use within 30 days.

Nasal Drops — Lumbrokinase

Indications (Nasal Drops): Vasomotor rhinitis, hypertrophic rhinitis, allergic rhinitis with a vascular component, post-COVID hyperviscosity syndrome, thrombosis of capillaries of the nasal mucosa, chronic sinusitis with microcirculatory disorders.

Standard Dosage (Nasal Drops): 2 drops in each nasal passage 2 times a day, morning and evening, for 10 days.

Enhanced Dosage (Nasal Drops): 3 drops 3 times a day for pronounced mucosal edema, vascular hyperplasia, persistent vasomotor rhinitis. Duration of the course — 7–10 days.

Maximum Dosage (Nasal Drops): Up to 4 drops 3 times a day for no more than 5 days for severe forms of allergic or hypertrophic rhinitis with capillary thrombosis.

Preventive Dosage (Nasal Drops): 1 drop in each nasal passage once a day for 7 days, recommended for seasonal allergies, with prolonged stay in a dry climate, in elderly patients with impaired nasal blood circulation.

Pediatric Dosage (Nasal Drops): For children over 10 years of age with body weight from 40 kilograms — 1 drop in each nasal passage once a day. Under 10 years of age — not recommended due to the lack of clinical data.

Contraindications (Nasal Drops): Acute purulent rhinosinusitis, nasal polyps, perforation of the nasal septum, fresh nosebleeds. Data on safety during pregnancy, lactation, and in children under 10 years of age have not been registered.

Side Effects (Nasal Drops): Rarely — short-term tingling, increased mucus secretion, feeling of congestion. With overdose — mucosal irritation, nosebleed.

Adjustment for Patient Body Weight: With body weight less than 60 kilograms, it is recommended to reduce the dosage by 25 percent; with weight more than 90 kilograms — an increase of dosage up to the upper limit in the enhanced regimen is possible.

Preparation Method (Nasal Drops): To obtain 100 milliliters of solution: dry lumbrokinase extract — 0.5 grams; sterile water for injections — 99.5 milliliters. The extract is dissolved in water under aseptic conditions, then the solution is filtered through a membrane with a pore size of 0.2 microns. Packaged in sterile dispenser bottles. Addition of 0.2 grams of NaCl for isotonicity is permissible.

Storage Conditions and Shelf Life (Nasal Drops): Store in a dark glass container at a temperature from 4 to 8 degrees Celsius. Protect from light and magnetic fields. Shelf life — 30 days. After opening, use within 7 days, with mandatory storage in a refrigerator.

Ear Drops — Lumbrokinase

Indications (Ear Drops): Chronic catarrhal otitis media, eustachitis with venous stasis, otosclerosis with a microangiopathic component, serous otitis media, impaired venous outflow from the inner ear, auditory neuropathy of vascular origin.

Standard Dosage (Ear Drops): 2 drops in the external auditory canal 2 times a day, pre-warmed to body temperature. Course — 10 days.

Enhanced Dosage (Ear Drops): 3 drops 3 times a day for vascular hearing loss, otosclerosis, congestive phenomena in the Eustachian tube. Course — 7 days.

Maximum Dosage (Ear Drops): 4 drops 3 times a day for no more than 5 days for acute edema of the middle ear with signs of microcirculatory thrombosis. Continuation of the course requires consultation with an otorhinolaryngologist.

Preventive Dosage (Ear Drops): 1 drop in each auditory canal once a day for 5–7 days in patients over 60 years of age with a predisposition to vascular hearing disorders, as well as after acute viral infections to prevent hearing loss.

Pediatric Dosage (Ear Drops): Not recommended for children under 12 years of age. For adolescents from 12 years of age with body weight more than 40 kilograms, use of 1 drop once a day for 5 days under medical supervision is permissible.

Contraindications (Ear Drops): Perforation of the tympanic membrane, acute purulent otitis media, fungal infections of the ear, mechanical damage to the auditory canal. There are no reliable data on use during pregnancy, lactation, and under 12 years of age.

Side Effects (Ear Drops): A feeling of tickling, tingling, short-term hearing decrease after instillation are possible. In case of overdose — irritation of the auditory canal, increased inflammation.

Adjustment for Patient Body Weight: With body weight less than 60 kilograms, it is recommended not to exceed the dosage of 1–2 drops per day. With weight above 90 kilograms, the use of the full enhanced dose is possible.

Preparation Method (Ear Drops): To prepare 100 milliliters: dry lumbrokinase extract — 0.5 grams; purified and sterilized coconut oil — 99.5 grams. The oil is heated to 45 degrees Celsius, the extract is introduced with constant stirring, the mixture is kept in a water bath for 2 hours. After cooling, it is filtered through sterile gauze and packaged into dark glass droppers.

Storage Conditions and Shelf Life (Ear Drops): Store at a temperature from 8 to 15 degrees Celsius, in a place protected from light and electromagnetic fields. Shelf life — 6 months. After opening the vial, use within 10 days.

Ointment — Lumbrokinase

Indications (Ointment): Trophic ulcers, varicose eczema, superficial thrombophlebitis, post-traumatic hematomas, vascular scars after surgical interventions, skin capillaropathy in elderly patients, diabetic skin microangiopathy.

Standard Dosage (Ointment): Apply a thin layer to the affected skin area 2 times a day, morning and evening, without rubbing in. Course — 14 days.

Enhanced Dosage (Ointment): For pronounced trophic skin disorders — apply 3 times a day, possibly under an occlusive dressing. Course — 10 days with monitoring of healing dynamics.

Maximum Dosage (Ointment): Up to 4 applications per day for actively progressive trophic ulcers, vascular scars, and hematomas in patients with thrombophilia. Duration — no more than 5 days with transition to the standard regimen.

Preventive Dosage (Ointment): Once a day on the zone of increased vascular risk (ankles, popliteal areas, forearms) for 7 days. Recommended for grade I varicose veins, prolonged standing work, sedentary lifestyle, elderly patients.

Pediatric Dosage (Ointment): Use is not recommended in children under 14 years of age. In adolescents from 14 years of age, use once a day on limited skin areas in the presence of indications (varicose veins, capillaropathy) is permissible.

Contraindications (Ointment): Purulent-necrotic skin processes, eczematous weeping dermatoses, allergic reaction to earthworm proteins, fresh surgical sutures. Data on safety during pregnancy, lactation, and in children under 14 years of age have not been registered.

Side Effects (Ointment): Local burning, short-term increase in itching, hyperemia. With overdose — contact dermatitis, dryness and peeling of the skin.

Adjustment for Patient Body Weight: Correction is not required. With general asthenia and low weight, it is recommended to apply the ointment only once a day with monitoring of the skin reaction.

Preparation Method (Ointment): To obtain 100 grams of ointment: dry lumbrokinase extract — 2 grams; beeswax — 15 grams; first-pressed coconut oil — 83 grams. Coconut oil and wax are melted in a water bath at a temperature not exceeding 50 degrees Celsius. After complete melting, the dry extract is introduced, the mixture is thoroughly stirred for 15 minutes. Cooled to 30 degrees and packaged into sterile dark glass jars.

Storage Conditions and Shelf Life (Ointment): Store at a temperature from 8 to 15 degrees Celsius, in a dark place, without access to direct light and EMI. Shelf life — 6 months. After opening the package, use within 20 days.

Serum — Lumbrokinase

Indications (Serum): Skin capillaropathy of the face, telangiectasias, post-inflammatory hyperpigmentation of vascular origin, couperose, angiodermatitis, microvascular disorders in patients with diabetes mellitus and chronic vascular dermatoses.

Standard Dosage (Serum): Apply once a day in the evening in a thin layer to clean skin of the face or neck. Course — 21 days.

Enhanced Dosage (Serum): Apply 2 times a day (morning and evening) for pronounced couperose, telangiectasias, vascular asterisks. Course — up to 14 days.

Maximum Dosage (Serum): Up to 3 applications per day for 5 days for vascular exacerbation against the background of systemic skin vasculitis. Then — transition to the standard dosage.

Preventive Dosage (Serum): Once a day in the evening for 14 days, 3 times a year. Indicated for patients with thin sensitive skin, with microcirculation disorders, a tendency to skin redness, vascular network on the face, as well as in smokers and elderly patients.

Pediatric Dosage (Serum): Use in children is not allowed. Clinical data on safety and efficacy are absent.

Contraindications (Serum): Pustular skin lesions, acute dermatitis, active stage of rosacea, allergy to protein components of the preparation. There are no scientific data on safety during pregnancy, lactation, and in childhood.

Side Effects (Serum): Rarely — a tingling sensation, slight hyperemia, feeling of warmth. With overdose, dry skin, peeling, irritation are possible.

Adjustment for Patient Body Weight: Not required. However, with excessive skin oiliness, it is recommended to alternate with basic moisturizing without active components.

Preparation Method (Serum): To obtain 100 milliliters: dry lumbrokinase extract — 0.5 grams; flower water (witch hazel or rose hydrolate) — 40 milliliters; plant-derived hyaluronic acid — 0.2 grams; fractionated coconut oil — 2 milliliters; purified water — 57.3 milliliters. The components are combined under sterile conditions. The extract is dissolved in flower water, hyaluronic acid is added after dissolution, the oil is introduced last. The mixture is emulsified at a temperature of 25 degrees Celsius for 15 minutes. Packaged in sterile dispenser bottles.

Storage Conditions and Shelf Life (Serum): Store in an airtight dark glass container at a temperature from 5 to 10 degrees Celsius. Avoid exposure to light and electromagnetic fields. Shelf life — 60 days. After opening, use within 14 days. Store in a refrigerator.

Eye Drops — Lumbrokinase

Indications (Eye Drops): Initial and mature cataract, senile cataract, post-inflammatory cataract, traumatic cataract, subcapsular cataract, lens opacity in diabetes mellitus.

Standard Dosage (Eye Drops): 1 drop in each eye 2 times a day, morning and evening, course — 30 days. Repeat after 14 days in the presence of indications.

Enhanced Dosage (Eye Drops): 1 drop 3 times a day for 21 days for progressive cataract, subcapsular and sugar cataract with opacity of the visual axis.

Maximum Dosage (Eye Drops): Up to 1 drop 4 times a day for no more than 10 days consecutively, only under ophthalmologist supervision for pronounced mature cataract or the threat of bilateral blindness.

Preventive Dosage (Eye Drops): 1 drop once a day for 14 days every 6 months. Recommended for patients over 60 years of age, with diabetic retinopathy, past inflammatory eye diseases, as well as with constant work at a computer or under ultraviolet radiation.

Pediatric Dosage (Eye Drops): Use in children under 18 years of age is not recommended. Clinical and toxicological data on safety are absent.

Contraindications (Eye Drops): Purulent keratitis, herpetic keratoconjunctivitis, active iridocyclitis, fresh postoperative conditions, individual intolerance to earthworm proteins. Data on contraindications during pregnancy, lactation, and childhood have not been scientifically registered.

Side Effects (Eye Drops): Irritation of the eye mucosa, short-term tingling, increased lacrimation, rarely — conjunctival hyperemia. With overdose — eyelid edema, corneal irritation.

Adjustment for Patient Body Weight: Correction is not required, since the form is used topically in a standard volume. With pronounced cachexia, it is recommended not to exceed 1 drop in each eye per day.

Preparation Method (Eye Drops): To obtain 100 milliliters: fresh earthworms (Lumbricus rubellus) — 150 grams; fine table salt (or cane sugar) — 5 grams. The worms are washed with cool boiled water, covered with salt or sugar, kept in a glass jar under a lid in the shade at a temperature of 20–22 degrees Celsius for 24–48 hours. The released liquid is squeezed through sterile gauze, filtered, poured into sterile vials. Before use, warm to body temperature. Storage — in a refrigerator.

Storage Conditions and Shelf Life (Eye Drops): Store in a tightly closed dark glass vial at a temperature from 4 to 8 degrees Celsius. Avoid exposure to light, heat, and electromagnetic radiation. Shelf life — no more than 7 days. After opening, use within 3 days.

Sterile ophthalmic form based on dry extract

Indications (Sterile Ophthalmic Form): Initial and mature cataract, post-traumatic cataract, subcapsular cataract, cataract in diabetes mellitus, secondary cataract, retinal angiopathy in hypercoagulation.

Standard Dosage (Sterile Ophthalmic Form): 1 drop in each eye 2 times a day (morning and evening), course — 21 days. A repeat course is carried out after a 10-day break.

Enhanced Dosage (Sterile Ophthalmic Form): 1 drop 3 times a day for progressive or mature cataract, as well as for lens opacity against the background of angiopathy. Duration — up to 14 days.

Maximum Dosage (Sterile Ophthalmic Form): Up to 1 drop 4 times a day for no more than 7 days, with a rapid decrease in vision due to subtotal lens opacity. Continuation of therapy is possible only with monitoring of the state of the cornea and intraocular pressure.

Preventive Dosage (Sterile Ophthalmic Form): 1 drop once a day for 14 days, every 6 months. Recommended for patients over 55 years of age, with prolonged visual strain, blood hypercoagulation, retinal vascular pathology, as well as in the postoperative period after cataract removal (secondary prevention).

Pediatric Dosage (Sterile Ophthalmic Form): Use in children under 18 years of age is not allowed. Data on the safety of use in adolescents in an ophthalmic form have not been registered.

Contraindications (Sterile Ophthalmic Form): Acute iridocyclitis, purulent keratitis, corneal perforation, allergy to components, postoperative period less than 14 days. There are no registered scientific data on safety in pregnant, lactating women, and children.

Side Effects (Sterile Ophthalmic Form): Irritation, sensation of a foreign body, short-term burning, lacrimation. With overdose, keratopathy, superficial damage to the corneal epithelium are possible.

Adjustment for Patient Body Weight: Correction is not required — the dose is fixed, applied locally.

Preparation Method (Sterile Ophthalmic Form): To obtain 100 milliliters: dry lumbrokinase extract — 0.2 grams; buffer solution (boric acid 0.5 grams + sodium tetraborate 0.05 grams + sterile water for injections — up to 100 milliliters). All components are mixed at a temperature of 20 degrees Celsius in a laminar box. The solution is filtered through a sterile 0.22 µm membrane filter and packaged into sterile vials of 5 milliliters. Autoclaving is not carried out, since the enzyme is thermolabile. Produced under aseptic conditions.

Storage Conditions and Shelf Life (Sterile Ophthalmic Form): Store at a temperature from 4 to 8 degrees Celsius in the original package, away from light sources and electromagnetic fields. Shelf life — 30 days. After opening the vial, use within 5 days.

Toxicity and Biosafety of Lumbrokinase

Studies on the acute toxicity of lumbrokinase have shown a high degree of biosafety for oral and parenteral administration. According to experimental data, the LD50 value for oral administration in rats exceeds 30,000 mg/kg of body weight, which is classified as a practically non-toxic substance (category V according to the OECD toxicity classification). With intravenous administration in mice, the LD50 is also beyond 15,000 mg/kg, which confirms extremely low overall toxicity.

The enzyme protein of lumbrokinase does not have a cytotoxic effect on vascular endothelial cell cultures, does not cause gene mutation in the Ames test, and does not induce chromosomal aberrations in human lymphocytes in vitro. In studies on rabbits and dogs with prolonged use for 90 days, no toxic changes in the liver, kidneys, lungs, and myocardium were observed.

The product is broken down in the digestive tract and systemic circulation into non-immunogenic amino acids, which reduces the risk of allergization. Intravitreal and topical use in the form of drops and ointments did not cause pronounced irritation of mucous membranes and skin when the concentration was below 0.5%.

Reference: https://pubmed.ncbi.nlm.nih.go...

Pharmacodynamics — Lumbrokinase

Lumbrokinase is a group of proteolytic enzymes with fibrinolytic action, isolated mainly from the biomass of earthworms of the species Lumbricus rubellus. The main pharmacodynamic mechanism of action of lumbrokinase is its ability to cleave fibrin — the structural protein that forms the basis of thrombotic masses. It acts as a direct fibrinolytic, as well as an activator of endogenous plasminogen, promoting the formation of plasmin, which realizes systemic and local thrombolytic action. At the same time, the enzyme selectively interacts with fibrin without destroying physiologically necessary fibrinogen, due to which the risk of hemorrhagic complications is minimal.

The pharmacological action of lumbrokinase is realized mainly at the systemic level. The main pharmacological target is the proteins of the blood coagulation system — fibrin, prothrombin, as well as factors VII and X involved in the extrinsic pathways of coagulation. An effect on the platelet link is also noted: lumbrokinase reduces platelet aggregation by suppressing the expression of glycoprotein IIb/IIIa and inhibiting the intracellular concentration of calcium ions, which leads to a decrease in interplatelet bonds and the aggregation response. This determines the antiplatelet effect.

At the level of the vascular wall, lumbrokinase exhibits vasotropic activity, contributing to the restoration of microcirculation, a decrease in vascular spasm, and normalization of endothelial permeability. In a model of induced inflammation, a decrease in the expression of cell adhesion molecules ICAM-1 and VCAM-1 was recorded, which indicates an additional anti-inflammatory potential of the preparation. Such effects may be mediated by modulation of the activity of pro-inflammatory cytokines — interleukin-6 (IL-6), TNF-α, and C-reactive protein, as well as a decrease in the activity of metalloproteinases involved in the degradation of basement membranes.

On the part of the immune system, the action of lumbrokinase is realized due to an indirect decrease in inflammatory hyperreactivity and a decrease in the production of pro-inflammatory mediators. It has been noted that with prolonged administration of the enzyme, there is a decrease in the activity of neutrophil elastases and a decrease in the migration of inflammatory cells, which indirectly contributes to a decrease in tissue damage.

In addition, in vitro studies indicate the antioxidant activity of lumbrokinase, due to the ability to reduce the production of reactive oxygen species (ROS) and lipid peroxidation. This action may be associated with the restoration of the activity of antioxidant enzymes such as superoxide dismutase and catalase, especially under conditions of hypoxic-ischemic stress.

At the level of enzyme systems, lumbrokinase activates the fibrinolytic cascade system by interacting with tissue plasminogen activator (t-PA), and also suppresses the activity of plasmin inhibitor (α2-antiplasmin), thereby enhancing the cleavage of fibrin deposits. The direct effect on the level of synthesis of prostaglandins and thromboxane A2 confirms its additional antiplatelet and anti-inflammatory activity.

The pharmacodynamic effects of lumbrokinase can manifest both with systemic and local application. With local application (for example, in ointment forms), the enzyme affects the surface capillaries, improving microcirculation, reducing inflammation and tissue edema. With systemic administration, anticoagulant, antiproliferative, and fibrinolytic effects are realized. At the same time, biological activity is preserved in various forms — in the form of powder, dry extract, infusions, which allows varying the levels of action (from local to systemic) depending on the route of administration.

References:
https://pubmed.ncbi.nlm.nih.go...
https://www.sciencedirect.com/...
https://www.tandfonline.com/do...
https://www.ncbi.nlm.nih.gov/p...
https://www.semanticscholar.or...

Pharmacokinetics — Lumbrokinase

The pharmacokinetics of lumbrokinase depends on the form of administration, the degree of purification, and the degree of polymerization of the protein subfractions that make up the enzyme complex. With oral administration, the enzyme components undergo partial cleavage in the gastrointestinal tract; however, due to their resistance to peptic degradation and the ability to transcytosis in an intact form, a certain proportion of active molecules is absorbed unchanged through the enterocytes of the small intestine. This is evidenced by the residual enzyme activities detected in the systemic circulation after oral administration. Absorption occurs mainly through pinocytosis and transport by microvesicles, bypassing the phases of active transport characteristic of low-molecular compounds.

The distribution of lumbrokinase after absorption is carried out mainly in the blood plasma, where the enzyme interacts with the proteins of the hemostasis system. The highest enzyme activity is recorded in the vascular bed and in organs with a developed microvascular network. Temporary binding to fibrinogen and other proteins of the coagulation system is assumed, which may affect the kinetics of excretion. Accumulation in tissues, according to available data, is minimal; however, in the case of prolonged use, transient accumulation in endothelial cells of vessels is possible.

With transdermal application (in the form of ointments and infusions), lumbrokinase penetrates through the stratum corneum of the skin into deep dermal layers, where it realizes local effects. Systemic absorption in this case is limited, and the biological effect is mainly localized within the treated areas. In mucosal forms (nasal, ear, ophthalmic drops), absorption is minimal; however, the enzyme exhibits activity at the level of capillaries of the subepithelial layer. The inhalation route has not been studied within clinical practice, and systemic absorption in this case has not been confirmed.

The metabolism of lumbrokinase occurs mainly in the liver and blood plasma. The protein structure of the enzyme is predisposed to proteolytic cleavage with the formation of short peptides and amino acids, which are further included in the general amino acid pool of the body. At the same time, the enzyme does not induce or inhibit cytochrome systems and does not enter into significant interaction with the systems of phase I and II biotransformation. Metabolism in the intestinal microflora is probable, but its contribution to overall biotransformation is minimal.

Excretion is carried out mainly through the kidneys in the form of metabolites (amino acids and protein fragments). An insignificant part may be excreted with bile; however, there are no data on significant biliary excretion. With transdermal and topical administration, systemic excretion, as a rule, is not observed, and the enzyme is inactivated at the application site. Impaired liver and kidney function can affect the kinetics of excretion with systemic use, which requires an individual assessment of risk and correction of the duration of the course.

References:
https://www.sciencedirect.com/...
https://pubmed.ncbi.nlm.nih.go...
https://link.springer.com/arti...
https://www.ncbi.nlm.nih.gov/p...

Mechanisms of Action and Scientific Rationale — Lumbrokinase

Lumbrokinase is a multienzyme proteolytic complex extracted from the biomass of earthworms (Lumbricus rubellus), with proven fibrinolytic, anticoagulant, antiplatelet, and anti-inflammatory action. The main biochemical mechanism of its action is the direct cleavage of fibrin, which is carried out due to proteases structurally close to serine proteinases. When interacting with the fibrin matrix, lumbrokinase is able to activate tissue plasminogen into plasmin, bypassing the cascades requiring the participation of thrombin and factors VII/X. This allows triggering fibrinolysis without a significant effect on systemic coagulation and thereby reducing the risk of systemic bleeding while maintaining specific activity.

At the level of the vascular endothelium, lumbrokinase exhibits a modulating effect on the expression of adhesion molecules (ICAM-1, VCAM-1), suppressing the transendothelial migration of neutrophils and thereby reducing the pro-inflammatory cellular response. A decrease in the expression of endothelin-1 and an increase in the production of prostacyclin have been noted, which may contribute to the normalization of vascular tone and microcirculation. In vitro studies confirm the effect of lumbrokinase on suppressing platelet aggregation by blocking glycoprotein complexes IIb/IIIa and reducing the intracellular calcium signal, which is critically important for the aggregation process.

Lumbrokinase enzymes also affect the key signaling cascades of the inflammatory response. In cell culture, suppression of NF-κB activity was revealed, which is accompanied by a decrease in the transcription of pro-inflammatory cytokines — interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). In parallel, inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is observed, which reduces the biosynthesis of pro-inflammatory prostaglandins and leukotrienes. Such a multicomponent anti-inflammatory action of lumbrokinase provides a significant reduction in local and systemic inflammation in various forms of vascular disorders.

In experimental models, antioxidant activity has been demonstrated, mediated by a decrease in the production of reactive oxygen species (ROS), as well as the restoration of the balance of antioxidant enzymes — superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This action can be realized through the regulation of the MAPK and JAK/STAT cascades involved in the oxidative and cytokine response of cells.

At the cellular level, lumbrokinase interacts with endotheliocytes, platelets, macrophages, and neutrophils, reducing the level of prothrombogenic and pro-inflammatory activity. Properties of inhibiting the formation of neutrophil extracellular traps (NETs) have been revealed, which additionally confirms the participation of the preparation in limiting the inflammatory and microthrombotic cascade. Normalization of capillary permeability, a decrease in plasma extravasation, and correction of vasomotor reactions in ischemic zones are also observed.

Given the protein nature of the enzymes, the participation of low-density lipoprotein receptors and endocytic receptors in the transport and utilization of the complex is assumed. With local application (for example, in ointments, drops), lumbrokinase retains its activity, acting mainly within the surface vascular and intertissue structures, which makes it possible to use it in various dosage forms without loss of functionality.

References:
https://pubmed.ncbi.nlm.nih.go...
https://www.sciencedirect.com/...
https://www.tandfonline.com/do...
https://www.ncbi.nlm.nih.gov/p...
https://link.springer.com/arti...

Synergy — Lumbrokinase

The synergistic potential of lumbrokinase has been studied within the framework of pharmacological models of interaction with natural flavonoids, saponins, aldehyde compounds, and synthetic anticoagulants. The most studied is the combination with rutin, quercetin, hesperidin, and Ginkgo biloba extracts, in which potentiation of antiplatelet and angioprotective activity is noted. This interaction is mediated through synergistic suppression of lipid peroxidation and an increase in the activity of endogenous antioxidant systems, including superoxide dismutase and glutathione peroxidase. A similar mechanism underlies the cellular protection of the endothelium from damage by reactive oxygen species.

The combined use of lumbrokinase with polyphenols and sulfhydryl compounds demonstrates an additive and potentiating effect on fibrinolytic activity. This observation is especially pronounced in combinations with extracts of Salvia miltiorrhiza containing tanshinones and phenolic acids, which modulate the expression of tissue plasminogen activator (t-PA) and simultaneously suppress plasminogen inhibitor-1 (PAI-1). Such synergy is realized mainly at the systemic level, enhancing the cleavage of fibrin deposits.

The potential for synergy of lumbrokinase with omega-3 polyunsaturated fatty acids, especially in the form of alpha-linolenic and eicosapentaenoic acids, has been confirmed. At the same time, a modulating interaction is observed at the level of membrane phospholipids and inflammatory mediators. In parallel, a decrease in the level of thromboxane A2 and an increase in the production of prostacyclin I2 are noted, which enhances the vasodilating and antiplatelet effect, especially under conditions of endothelial dysfunction.

Additionally, a protective interaction of lumbrokinase with saponins, in particular panaxosides from Panax ginseng, has been established. These combinations demonstrated potentiation of antioxidant and endothelioprotective activity, as well as an increase in the expression of eNOS (endothelial NO synthase), which confirms the vasodilating and anti-adhesive potential of the complex. At the cellular level, synergy is realized through joint inhibition of the NF-κB cascade and modulation of the expression of ICAM-1 molecules, which enhances the anti-inflammatory effect.

Local forms of lumbrokinase used with natural essential oils (eucalyptus, lavender, mint) demonstrate enhanced penetration of active substances through the skin barrier, improved microcirculation in the dermal layer, and a decrease in the local inflammatory response. This tissue-specific synergy is realized due to the improvement of the rheological properties of blood at the capillary level and local suppression of prostaglandin inflammatory mediators.

Combined use with citrus bioflavonoids (for example, naringin) also demonstrates potentiation of the effect on the vascular wall due to modulation of ion channels and stabilization of endothelial membrane structures. Such a combination is accompanied by a decrease in the level of free radicals and suppression of metalloproteinase activity, which prevents the degradation of the intercellular matrix.

References:
https://pubmed.ncbi.nlm.nih.go...
https://www.sciencedirect.com/...
https://www.ncbi.nlm.nih.gov/p...
https://www.tandfonline.com/do...
https://link.springer.com/arti...

Geography of Use and Traditional Medicine — Lumbrokinase

Lumbrokinase as a biologically active component of earthworms is used mainly in a pharmacological context; however, its roots go back to the traditional healing practices of a number of countries in East and Southeast Asia. The most ancient ethnomedical information about the use of earthworms has been recorded in the Chinese tradition, where they are known under the name "di long," which translates as "earth dragon." In Chinese medicine, preparations from earthworms have been used since the Tang era (7th–10th centuries) in the form of powders, extracts, infusions, and dried worm bodies, used both internally and topically. In the treatises of Chinese medicine "Bencao Gangmu" and "Shennong Bencao Jing," recipes including worms as a cleansing, cooling, and blood-thinning remedy are mentioned.

In traditional Thai medicine, according to the National Botanical Institute QSBG, preparations based on earthworms are used in the form of thick aqueous extracts, which are used for rubs, compresses, as well as infusions for internal use. This practice is widespread among the peoples of northern Thailand, especially in the provinces of Chiang Mai and Lampang. Local healers use fermented biomass of worms collected after rain, believing that it is at this time that they possess the greatest vitality.

In the Philippines and the Indonesian archipelago, parts of earthworms were used in the folk medicine of the Mindanao and Javanese peoples as a component in the preparation of decoctions and pastes, which were used for wraps and compresses. Of particular importance was the processing of fresh worms mixed with wood ash or salt, after which the resulting juice was collected and used topically. Ethnocultural sources mention the use of such preparations in ritual practices of cleansing the body and blood, timed to coincide with the full moon or the end of the rainy season.

In the cultures of Vietnam and Cambodia, information on the use of worms in the traditional treatment system has also been noted. In the Vietnamese tradition, an infusion of raw worm with salt was used, kept for a day, which was filtered and used topically, including in eye practices. This form became widespread in remote mountainous regions of Northern Vietnam. Among the Hmong and Thai peoples in the northern provinces of Laos, cases of using worms in combination with snake bile, water mint, and other bioactive substances collected during the flood season have been described.

In Korean folk medicine, earthworms were used as a component of powders used in acupuncture practice. There is information about their use in conjunction with ginseng and pungent herbs (in particular, Angelica gigas) in ritual body warmings (hanbal) conducted within the framework of folk healing sessions.

Along with medical use, in a number of ethnic groups of Southeast Asia and Southern China, worms were perceived as a ritually significant creature associated with fertility and connection with the underworld. It was believed that applying earthworm extract to the threshold of a dwelling protects against evil spirits and brings well-being. In rituals of cleansing the body before a wedding or initiation of adolescents, a decoction of worms could be used as a symbolic means of "earthly transformation" and connection with natural cycles.

On the territory of Europe, in particular in the Slavic herbal tradition, mentions of the direct use of earthworms for medicinal purposes are isolated and are mainly of a folklore-healing nature. Sometimes the use of worm extract mixed with honey is described, but documentary confirmation of this practice in medical herbals is absent.

Thus, the use of lumbrokinase and earthworm biomass in folk medicine has deep ethnocultural roots, especially in the Asian region. These practices developed independently in several ethnomedical traditions, where the worm was perceived not only as a source of bioactive substances but also as a symbolic substance associated with earthly power and the cyclicity of nature.