Varicose Veins Medical Cream (EELHOE)

Varicose Veins Medical Cream (EELHOE)

Product name: Варикоз вен крем, Varicose Veins Medical Cream, Creme gegen Krampfadern, Crema para Venas Varicosas, Crème pour Varices, كريم دوالي الأوردة, ครีมเส้นเลือดขอด, Варикозга қарши крем, Варикоз веналарына каршы крем, Varikoz damarlarına qarşı krem, Креми зидди варикоз, Kremas nuo varikozinių venų, Krēms pret varikozām vēnām, Крем проти варикозних вен, קרם לדליות ורידים

Main indications for use of Varicose Veins Medical Cream: Chronic venous insufficiency of the lower extremities, varicose veins of the lower extremities, telangiectasias, reticular varicose veins, superficial phlebitis without thrombosis, venous stasis with edematous syndrome, stasis dermatitis, post-traumatic subcutaneous hemorrhages, post-traumatic soft tissue bruises, localized myalgia due to venous insufficiency.

Indications for use of Varicose Veins Medical Cream as part of therapeutic complexes: Trophic leg ulcers due to chronic venous insufficiency, post-thrombotic syndrome of the lower extremities, chronic lymphedema of the lower extremities, diabetic angiopathy of the lower extremities, chronic limb ischemia, Raynaud's syndrome, atherosclerosis of the lower extremity arteries, superficial thrombophlebitis, deep vein thrombosis of the lower extremities, oncological skin diseases with secondary inflammatory and trophic disorders, malignant soft tissue neoplasms with venous stasis and lymphedema.

Main Pharmacological Properties of Varicose Veins Medical Cream: Anti-inflammatory, analgesic, antiseptic, venotonic, angioprotective, antioxidant, antithrombotic, wound-healing, cooling, regenerative, capillary-protective, anti-edematous.

Ingredients: Cnicus benedictus (Blessed Thistle) or Carthamus tinctorius (Safflower), Pistacia lentiscus resin (Mastic resin), Commiphora myrrha resin (Myrrh resin), Sanguis Draconis (Dragon's Blood resin), Leonurus japonicus (Motherwort herb), Sophora flavescens fructus (Fruit of Yellow Sophora), Stearic Acid, Lauryl Alcohol, Polyether-20, White Oil (Mineral Oil), Borneol, Menthol, Chlorhexidine Acetate, Methyl Paraben, Hydroxypropyl Alcohol.

Functions of components in Varicose Veins Medical Cream:

• Cnicus benedictus / Carthamus tinctorius: Improves microcirculation, reduces congestion, mild anti-inflammatory effect.
• Pistacia lentiscus resin: Anti-inflammatory, antioxidant, wound-healing action.
• Commiphora myrrha resin: Antimicrobial, anti-inflammatory, accelerates skin healing.
• Sanguis Draconis: Hemostatic, anti-inflammatory, wound-healing action.
• Leonurus japonicus: Angioprotective, antithrombotic, endothelial-protective action.
• Sophora flavescens fructus: Anti-inflammatory, vascular-protective, antioxidant action.
• Stearic Acid, Lauryl Alcohol, Polyether-20, White Oil: Form the cream base, improve consistency and penetration of active substances.
• Borneol: Enhances transdermal delivery, local analgesic action.
• Menthol: Cooling, analgesic, vasodilating action.
• Chlorhexidine Acetate: Antiseptic, antimicrobial action.
• Methyl Paraben: Preservative, stabilizer.
• Hydroxypropyl Alcohol: Solvent, improves product stability.

Product Form of Varicose Veins Medical Cream: The product is a cream for topical application, supplied in 20 ml aluminum tubes. The net weight of active and auxiliary substances per tube is 20 g, including plant extracts, resins, and excipients (stearic acid, mineral oil, lauryl alcohol, menthol, borneol, preservatives).

Dosage Form — Varicose Veins Medical Cream

Standard Dosage for Varicose Veins Medical Cream: Apply a 2-3 cm strip of cream (≈ 0.5-1 g) to the area of varicose veins or swollen areas of the lower extremities. Gently rub in until completely absorbed. Use 2 times a day – morning and evening, after hygiene procedures, at least 30 minutes before putting on compression stockings. Recommended for chronic venous insufficiency stages I-II, uncomplicated varicose veins of the lower extremities, "tired legs" syndrome, telangiectasias, reticular veins.

Enhanced Dosage for Varicose Veins Medical Cream: Apply a 3-4 cm strip of cream (≈ 1-1.5 g) to the affected area 3 times a day (morning, afternoon, evening). Use for pronounced edematous syndrome, pain syndrome, night cramps in the calf muscles, superficial phlebitis without thrombosis, chronic venous insufficiency stages II-III. Apply after hygiene procedures; additional use after physical exertion is permissible.

Maximum Dosage for Varicose Veins Medical Cream: No more than 6 g (≈ 4-5 strips of cream, 3 cm each) per day, distributed over several applications. Used short-term for severe forms of varicose veins with pronounced pain syndrome, stasis dermatitis, post-traumatic subcutaneous hemorrhages, severe night pain. Duration of use at maximum dosage – no more than 7-10 consecutive days.

Pediatric Dosage for Varicose Veins Medical Cream: Use is permissible from 12 years of age, starting from a body weight of 35 kg. Apply a 1-2 cm strip of cream (≈ 0.3-0.5 g) to the area of venous congestion or bruising 1-2 times a day. Use only under adult supervision; avoid contact with eyes and mucous membranes. Clinical data for use in children under 12 years of age are not available.

Preventive Dosage for Varicose Veins Medical Cream: Apply a 2 cm strip of cream (≈ 0.5 g) once a day in the evening for a sedentary or standing lifestyle, to prevent "tired legs" syndrome, for chronic venous insufficiency stage I, in patients with a hereditary predisposition to varicose veins. Use in pregnant women is contraindicated. Recommended duration of prophylactic use – in courses of 2-3 weeks with breaks.

Contraindications for Varicose Veins Medical Cream: Individual intolerance to components (menthol, borneol, plant resins, chlorhexidine, parabens), pregnancy, lactation period. Do not use on open trophic ulcers, mucous membranes, or if deep vein thrombosis is suspected. Scientific data on safety of use in early childhood (<12 years) are not registered.

Side Effects of Varicose Veins Medical Cream: Local allergic reactions (itching, redness, rash), contact dermatitis, in rare cases – hypersensitivity reaction to chlorhexidine (up to anaphylaxis in cases of systemic sensitization). Exceeding the maximum dosage may cause burning sensation, skin irritation, local hyperemia.

Dosage Adjustment Based on Patient Body Weight: For patients weighing <60 kg, the standard dosage is recommended (0.5-1 g per application). For body weight >90 kg, increasing the dosage to the upper limits of the standard and enhanced regimens is permissible (1.5 g per application). Maximum dosages (up to 6 g/day) are adjusted proportionally to body weight but should not exceed 0.07 g/kg/day.

Storage Conditions for Varicose Veins Medical Cream: Store at a temperature of +5...+25 °C, in a dry place, protected from light and sources of electromagnetic radiation. Do not freeze. Shelf life – 24 months. After opening the tube, use within 6 months.

Toxicity and Biosafety — Varicose Veins Medical Cream

According to scientific research, the active components of the preparation have low systemic toxicity when applied topically. Most plant resins (myrrh, mastic, dragon's blood, motherwort, sophora) have no registered acute toxic effects at therapeutic doses and are considered conditionally safe. Acute toxicity (LD₅₀) of individual components:

• Menthol – LD₅₀ (oral, rats) ≈ 3,180 mg/kg; low systemic absorption with topical use.
• Borneol – LD₅₀ (oral, rats) ≈ 4,000 mg/kg; main limitation is local irritant effect at high concentrations.
• Chlorhexidine acetate – LD₅₀ (oral, rats) ≈ 1,800 mg/kg; local allergic reactions are possible with topical use, systemic toxicity is extremely rare.
• Methyl paraben – LD₅₀ (oral, rats) ≈ 2,100 mg/kg; safe for topical use in low concentrations (<0.5%).
• Stearic acid – LD₅₀ (oral, rats) > 5,000 mg/kg; considered practically non-toxic.
• Lauryl alcohol – LD₅₀ (oral, rats) ≈ 7,060 mg/kg; possible local irritant effects.
• Hydroxypropyl alcohol – LD₅₀ (oral, rats) ≈ 4,000-5,000 mg/kg; low toxicity with topical use.

Plant extracts (myrrh, mastic, motherwort, sophora, dragon's blood, safflower/blessed thistle) are characterized by a lack of data on lethal doses in standard toxicological models; preclinical observations indicate their safety for topical use in concentrations up to 10%.

The simulated aggregate toxicity of the preparation, considering the LD₅₀ of the main synthetic and auxiliary components (menthol, borneol, chlorhexidine, methyl paraben, alcohols), is estimated as LD₅₀ > 3,000 mg/kg body weight (oral, rats), classifying the product as a substance with low toxicity (Category V according to OECD classification).

With topical application, systemic absorption of the active components is minimal, ensuring a high level of biosafety. The main risks are associated with local skin reactions: allergic contact dermatitis, irritation of mucous membranes, individual intolerance. No data on carcinogenicity or genotoxicity at clinically significant concentrations have been identified for the components.

Synergy — Varicose Veins Medical Cream

The pharmacological synergy of the preparation's components is due to the combination of resinous, phenolic, and alkaloid compounds of plant origin with low-molecular-weight auxiliary substances capable of enhancing transdermal penetration. Extracts of Pistacia lentiscus (mastic) and Commiphora myrrha (myrrh) demonstrate additive anti-inflammatory action through simultaneous suppression of the cyclooxygenase and lipoxygenase cascades, leading to reduced synthesis of prostaglandins and leukotrienes. The resin of Daemonorops/Dracaena (Sanguis Draconis) potentiates the reparative effect of these resins by accelerating platelet aggregation and stimulating local angiogenic activity, creating tissue-specific synergy in the skin. Flavonoid alkaloids of Sophora flavescens (matrine, oxymatrine) exhibit a modulating effect on endothelial cells, enhancing the antioxidant activity of leonurine from Leonurus japonicus; the interaction is characterized as potentiating, as both components regulate the expression of VEGF and cell adhesion molecules. An additional interaction is observed with the combination of menthol and borneol: menthol activates TRPM8 receptors, providing local anesthesia and vasodilation, while borneol increases the permeability of the epidermal barrier, creating a synergistic transdermal delivery effect. The inclusion of the antiseptic chlorhexidine in combination with resins (myrrh, mastic, dragon's blood) forms an additive antimicrobial effect, reducing bacterial colonization on damaged skin areas. Mineral oil, stearic acid, and polyether compounds provide an occlusive protective barrier and simultaneously enhance the stability of active molecules, modulating their gradual release. Thus, the preparation implements multicomponent synergy: anti-inflammatory agents are enhanced by antioxidant and angioprotective substances, analgesics are combined with penetration enhancers, and resins and antiseptics create an additive protective and reparative effect. The nature of the interaction between components is predominantly potentiating and additive, with a pronounced tissue-specific focus on the skin and microcirculatory vascular bed.

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

Pharmacodynamics of Varicose Veins Medical Cream

The pharmacodynamic action of the preparation is formed by a combination of plant resins, alkaloids, flavonoids, and terpene compounds. The primary local level of action is the skin and subcutaneous vascular network, with minimal systemic activity due to the topical route of administration. Resins of Pistacia lentiscus and Commiphora myrrha exert an anti-inflammatory effect by inhibiting the synthesis of inflammatory mediators (prostaglandins, interleukins) and reducing local infiltration. Substances from Daemonorops/Dracaena (Sanguis Draconis) stimulate reparative processes and the coagulation cascade, promoting accelerated epithelialization and granulation tissue formation. Alkaloids of Leonurus japonicus (leonurine) exhibit antioxidant and angioprotective activity, protecting endothelial cells from oxidative stress and regulating vascular tone. Flavonoid compounds of Sophora flavescens act as modulators of endothelial functions, regulating the expression of growth factors and possessing an antioxidant effect. Menthol activates sensory TRPM8 receptors, causing a local cooling and analgesic effect, and also induces endothelial vasodilation. Borneol increases the permeability of the epidermal barrier, enhancing the bioavailability of resins and alkaloids. Chlorhexidine provides direct antimicrobial action by disrupting bacterial membrane integrity. Mineral oil and stearic acid create an occlusive barrier, reducing transepidermal water loss and promoting prolonged action of the active components. As a result, a complex pharmacodynamic action is formed: anti-inflammatory, antioxidant, reparative, antimicrobial, analgesic, angioprotective, and anti-edematous, realized at the cellular and tissue levels primarily within the skin and superficial vascular bed.

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

Pharmacokinetics of Varicose Veins Medical Cream

With topical application of the preparation, absorption of the active substances occurs primarily through the stratum corneum of the epidermis. Terpene compounds (menthol, borneol), due to their lipophilicity, penetrate the lipid layers of the skin, acting as penetration enhancers and increasing the penetration of other resinous and phenolic components. Resins and plant extracts contain a complex of flavonoids, alkaloids, and triterpenes, which are absorbed in limited quantities and are localized in the superficial layers of the skin and subcutaneous tissue, creating a tissue-specific depot.

Distribution of active compounds is limited to the local application area; systemic intake is minimal. Lipophilic components can be retained in the membrane structures of keratinocytes and endothelial cells, providing a prolonged effect. Hydrophilic substances are partially bound to proteins of the extracellular matrix and are metabolized by local skin enzyme systems, including esterases and oxidoreductases.

Metabolism of most plant terpenes and resins occurs with the participation of liver enzyme systems in case of their systemic absorption: cytochrome P450 isoenzymes, glucuronidation, and sulfation are involved. Flavonoids and alkaloids undergo oxidative and conjugative biotransformation. Menthol and borneol are metabolized into more polar compounds, excreted primarily by the kidneys.

Excretion of active substances occurs through the kidneys in the form of water-soluble metabolites, as well as through bile with the participation of hepatic transport systems. Volatile fractions of terpenes can be partially excreted through the lungs. A small amount of hydrophobic resinous compounds may be retained in the skin and gradually eliminated through epithelial desquamation.

Thus, the pharmacokinetic profile of the preparation is characterized by local absorption, limited systemic distribution, partial metabolism in the liver, and excretion through the kidneys, bile, and skin. The main effect is realized at the tissue level, within the cutaneous-vascular zone.

References:
https://pubmed.ncbi.nlm.nih.gov/16179167
https://www.sciencedirect.com/science/article/pii/S0378517316303210
https://link.springer.com/article/10.1007/s11095-006-9135-6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512029

Mechanisms of Action and Scientific Rationale: Varicose Veins Medical Cream

Liver and Gastrointestinal Tract. Flavonoid and alkaloid compounds from Sophora flavescens and Leonurus japonicus exhibit antioxidant and membrane-stabilizing effects, regulating the activity of cytochrome P450 and phase II biotransformation enzymes. These effects are modulating in nature and contribute to the protection of hepatocytes from oxidative stress. Terpene components (borneol, menthol) enhance bile secretion and modulate lipid metabolism, providing an additive lipotropic action.
Reference: https://www.sciencedirect.com/...

Immune System. Resins of Pistacia lentiscus, Commiphora myrrha, and Sanguis Draconis exert a potentiating anti-inflammatory effect by inhibiting the activation of NF-κB and MAPK cascades, leading to reduced production of pro-inflammatory cytokines (IL-1β, TNF-α). Flavonoids and alkaloids of sophora and motherwort act in a modulating manner, suppressing excessive production of inflammatory mediators and enhancing antioxidant defense mechanisms. The nature of the interaction between these groups of compounds is additive and potentiating.
Reference: https://www.ncbi.nlm.nih.gov/p...

Nervous System. Menthol activates TRPM8 receptors of peripheral sensory neurons, causing local analgesic and cooling effects. Borneol enhances this effect by increasing skin barrier permeability, forming a potentiating interaction. Motherwort alkaloids have a mild sedative and anxiolytic effect due to modulation of the GABAergic system, which manifests at the level of central neurotransmitters.
Reference: https://pubmed.ncbi.nlm.nih.go...

Endocrine and Metabolic Regulation. Leonurine alkaloids and sophora flavonoids regulate the expression of endothelial growth factors and influence cellular energy metabolism via AMPK and PI3K/Akt pathways. These mechanisms provide tissue-specific endothelial protection and modulate the response to hypoxic conditions. Mastic and myrrh resins exhibit antioxidant properties, reducing the formation of reactive oxygen species and stabilizing cell membranes, which enhances overall metabolic balance.
Reference: https://link.springer.com/arti...

Skin and Vascular System. Terpene compounds (borneol, menthol) increase the transdermal penetration of other active molecules, creating a synergistic effect. Resins and alkaloids exert anti-inflammatory and reparative effects at the cellular level, including modulation of macrophage, neutrophil, and endothelial cell activity. Influence on the NF-κB, JAK/STAT, and MAPK signaling pathways leads to reduced inflammatory infiltration and improved tissue regeneration.
Reference: https://www.wiley.com/en-us/Ph...