Antifungal Spray (NHERB)

Antifungal Spray (NHERB)

Product Name: Грибковые поражения спрей с Zingiber cassumunar (плай), Citrus hystrix (каффир-лайм), Cuscuta reflexa (повилика), Antifungal Spray, Spray gegen Hautpilz, Aerosol contra infecciones fúngicas cutáneas, Spray antifongique pour les infections cutanées, بخاخ مضاد للفطريات الجلدية, สเปรย์รักษาเชื้อราที่ผิวหนัง, Qo‘ziqorinli teri kasalliklariga qarshi sprey, Теринин козу карын ооруларына каршы спрей, Dərinin göbələk infeksiyalarına qarşı sprey, Спрей зидди замбуруғи пӯст, Purški nuo odos grybelio, Pretsēnīšu aerosols ādas infekcijām, Спрей проти грибкових уражень шкіри, תרסיס נגד פטרת עור

Main Indications for Use of Antifungal Spray: Dermatophytosis of smooth skin, tinea pedis (athlete's foot), tinea cruris (jock itch), cutaneous candidiasis, intertriginous fungal infections, pityriasis versicolor, candidiasis of the oral mucosa and angular cheilitis (perlèche), candidal intertrigo.

Indications for Use of Antifungal Spray as Part of Therapeutic Complexes: Psoriasis with secondary fungal infection, atopic dermatitis with fungal colonization, seborrheic dermatitis with Malassezia infection, secondarily infected eczema, microbial eczema, chronic recurrent cutaneous and mucosal candidiasis, squamous cell skin cancer and melanoma with secondary fungal infection.

Main Pharmacological Properties of Antifungal Spray: antifungal, anti-inflammatory, analgesic, antiseptic, antibacterial, reparative, drying, deodorizing, immunomodulatory.

Composition of Antifungal Spray: Cuttle bone, Cuscuta reflexa Roxb., Citrus hystrix DC, Zingiber cassumunar Roxb., Other herbal ingredients.

Functions of the Components in Antifungal Spray:

• Cuttle bone: regulates skin surface pH, exerts a drying and adsorbing effect, reduces skin maceration in intertriginous mycoses.
• Cuscuta reflexa (Dodder): exerts antifungal action against Candida spp. and dermatophytes, additionally reduces skin inflammation and irritation.
• Citrus hystrix (Kaffir Lime): essential oils provide a pronounced antifungal and antimicrobial effect, eliminate odor, promote the healing of skin cracks.
• Zingiber cassumunar (Plai): rich in phenylbutenoids with pronounced anti-inflammatory and analgesic action, enhances the antifungal effect, accelerates skin regeneration.
• Other herbal ingredients: enhance the complex antimicrobial and reparative action, support the skin's barrier function.

Product Form of Antifungal Spray: The preparation is released in a spray bottle of 60 ml, containing a liquid phytocomplex. One spray dose (~0.12 ml) includes a standardized mixture of Cuttle bone (calcium carbonate), Cuscuta reflexa extract, Citrus hystrix oil, Zingiber cassumunar extract, and auxiliary herbal ingredients. The total weight of active substances in one bottle is about 60 g. It is used for fungal infections of the skin and mucous membranes of various localizations, including dermatophytoses, cutaneous candidiasis, and intertriginous lesions.

Dosage of Antifungal Spray

Standard Dosage for Antifungal Spray: For adult patients, it is recommended to apply 2-3 sprays (0.25-0.35 ml) to the affected skin area 2 times a day — morning and evening. The standard dosage is indicated for mild to moderate dermatophytosis of smooth skin, initial stage tinea pedis, intertriginous fungal infections, cutaneous candidiasis. Apply after hygienic cleaning of the affected area, without combination with activators.

Enhanced Dosage for Antifungal Spray: For adult patients with extensive skin lesions and chronic mycoses, apply 3-4 sprays (0.4-0.5 ml) 3 times a day — morning, afternoon, and evening. The enhanced dosage is recommended for tinea pedis with pronounced maceration, tinea cruris, chronic cutaneous candidiasis, and pityriasis versicolor with a recurrent course. For external use only, after drying the skin.

Maximum Dosage for Antifungal Spray: No more than 5 sprays (0.6-0.8 ml) per one lesion site up to 4 times a day. The maximum dosage is indicated for resistant dermatophytoses, chronic recurrent cutaneous candidiasis, multiple foci of mycosis in immunodeficiency states. Use in courses of no more than 14 days consecutively with subsequent assessment of clinical effect.

Pediatric Dosage for Antifungal Spray: Used in children over 6 years of age with a body weight of at least 20 kg. It is recommended to use 1-2 sprays (0.12-0.2 ml) 1-2 times a day on the affected skin area, preferably in the evening after hygiene procedures. For children under 6 years and with body weight less than 20 kg, safety data is insufficient; use is not recommended.

Preventive Dosage for Antifungal Spray: For patients with chronic diseases (diabetes mellitus, peripheral vascular insufficiency), as well as for individuals prone to frequent recurrences of fungal infections (athletes, bath and pool workers), preventive application of 1-2 sprays (0.12-0.2 ml) once a day in the evening on skin areas prone to maceration (feet, groin folds) is recommended. The duration of the preventive course is 7-10 days monthly.

Contraindications for Antifungal Spray: Individual hypersensitivity to the components of the preparation (Zingiber cassumunar, Citrus hystrix, Cuscuta reflexa, cuttle bone, etc.). Data on contraindications during pregnancy, lactation, and in children under 6 years of age have not been registered in the scientific literature.

Side Effects of Antifungal Spray: Scientifically registered side effects in case of overdose: local skin irritation, hyperemia, burning sensation, contact dermatitis. With prolonged use in high doses, excessive drying of the skin is possible.

Dosage adjustment based on patient body weight: For patients with body weight below 60 kg, it is recommended to limit application to 1-2 sprays per lesion site no more than 2 times a day. For patients with body weight above 60 kg, application of up to 3-4 sprays per lesion site up to 3 times a day is permissible.

Storage Conditions for Antifungal Spray: Store in the spray bottle at a temperature from +5 °C to +25 °C, in a dry place, protected from direct sunlight. Avoid exposure to electromagnetic sources (microwave ovens, industrial emitters). Shelf life of the closed package is 24 months. After opening the package, use within 6 months.

Toxicity and Biosafety – Antifungal Spray

Scientific studies on individual components of the preparation show low toxicity and a satisfactory biosafety profile.

• Zingiber cassumunar (Plai): Rhizome extracts have low acute toxicity, LD₅₀ (per os, mice) is more than 5 g/kg body weight. Studies revealed no carcinogenic or mutagenic effects.
• Citrus hystrix (Kaffir Lime): Essential oil upon oral administration has an LD₅₀ in mice of about 4-5 g/kg body weight. Moderate irritating activity upon topical application to mucous membranes is possible.
• Cuscuta reflexa (Dodder): Aqueous and alcoholic extracts have an LD₅₀ (per os, rats) of more than 3 g/kg body weight. Low toxicity and absence of teratogenic effects at standard dosages are noted.
• Cuttle bone: Represents biogenic calcium carbonate, safe in doses up to 8-10 g/kg body weight in laboratory animals. Used as a feed additive and in medical powders.

Modeled Cumulative Toxicity of the Complex: Considering the total concentrations of active components and their LD₅₀, the presumed acute toxicity of the preparation upon oral administration (which does not correspond to the therapeutic route) exceeds 3.5-4 g/kg body weight, classifying it as a low-toxicity substance (WHO Class IV toxicity).

Synergy – Antifungal Spray

The pharmacological synergy of the preparation's components is formed due to the combination of phytochemical molecules of different nature — phenylbutenoids from Zingiber cassumunar, terpenes from Citrus hystrix, flavonoids and lignans from Cuscuta reflexa, and the mineral matrix of cuttle bone (calcium carbonate). Studies have shown that essential oils from plants of the Zingiberaceae and Rutaceae families can exhibit additive and potentiating effects when used together. For instance, the phenylbutenoid DMPBD from Zingiber cassumunar demonstrates pronounced anti-inflammatory activity by inhibiting prostaglandin synthesis and reducing COX-2 expression. Simultaneously, citronellal, limonene, and β-citronellol from Citrus hystrix enhance the antimicrobial effect by disrupting the integrity of microbial cell membranes. The combination of these compounds leads to potentiation at the cellular level: inflammatory cascades are blocked simultaneously at the stage of mediator synthesis and at the level of membrane damage to pathogens.

Cuscuta reflexa contributes additionally due to the presence of phenolic compounds with antioxidant and immunomodulatory action. Their synergy with phenylpropanoids from Zingiber cassumunar provides a modulating effect on cytokine production and regulation of macrophage activity, forming a protective and normalizing mechanism at the tissue level. The combined action of these plants is characterized not only by an additive effect but also by potentiation: inhibition of inflammatory mediators is enhanced, and oxidative stress is reduced due to the combination of phenolic antioxidants and terpenes.

The role of cuttle bone is to create an alkaline environment and adsorb excess moisture, which reduces the possibility of microbial colonization and increases the bioavailability of phytochemical components on the skin surface. This can be considered as a modifying synergy: the mineral component provides favorable conditions for the activity of plant extracts, enhancing their biological action.

Thus, the nature of the ingredient interaction can be characterized as potentiating and modulating. The combined influence on inflammatory mediators, membrane structures, and local immune regulation forms a complex systemic and tissue-specific effect. The main directions of synergy are enhancement of antimicrobial activity, potentiation of anti-inflammatory action, and complementation of antioxidant and immunomodulatory effects. At the cellular level, this is realized through co-inhibition of inflammatory mediators, destruction of pathogen cell membranes, and enhancement of antioxidant protection.

References: PMC (pmc.ncbi.nlm.nih.gov), PubChem (pubchem.ncbi.nlm.nih.gov), ScienceDirect (sciencedirect.com), SpringerLink (link.springer.com), Wiley Online Library (onlinelibrary.wiley.com).

Pharmacodynamics of Antifungal Spray

The pharmacodynamic profile of the preparation is determined by the combined action of phenylbutenoids, terpenes, flavonoids, and mineral calcium carbonate. The primary level of action is local, on the skin and mucous membranes, however, some effects are realized through systemic mechanisms via influence on inflammatory mediators and cellular signaling pathways.

Phenylbutenoids from Zingiber cassumunar exert anti-inflammatory and analgesic action by inhibiting cyclooxygenase-2 and suppressing prostaglandin production. These compounds also reduce the release of pro-inflammatory cytokines (IL-1β, TNF-α), which manifests as a pronounced modulation of the local inflammatory response. Terpenes from Citrus hystrix act at the cellular level, disrupting the membrane permeability of microorganisms, inhibiting energy metabolism in microbial cells, and causing their death. Additionally, they exhibit antioxidant properties, binding reactive oxygen species and preventing lipid peroxidation in cell membranes.

Flavonoids and lignans from Cuscuta reflexa exert an immunomodulatory effect, influencing the activity of macrophages and NK cells, enhancing phagocytosis, and modulating interleukin production. This mechanism complements the antimicrobial and anti-inflammatory action of other components. The mineral component (cuttle bone, calcium carbonate) regulates local pH, creates unfavorable conditions for microbial growth, adsorbs exudate, and thereby reduces the risk of skin maceration.

The combination of these mechanisms forms a multi-component action: antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and reparative. Target systems include the skin and mucous membranes, the local immune system, enzymatic cascades of inflammation and oxidative stress, as well as cellular membranes of microorganisms. The pharmacodynamics are characterized by tissue specificity and local activity with minimal systemic impact.

References: PubMed (pubmed.ncbi.nlm.nih.gov), Semantic Scholar (semanticscholar.org), WHO monographs on medicinal plants (apps.who.int), SpringerLink (link.springer.com), Taylor & Francis Online (tandfonline.com).

Pharmacokinetics of Antifungal Spray

The pharmacokinetic properties of the preparation are determined by the route of administration and the chemical nature of the active components. With topical application, the main routes of absorption are transdermal and through mucous membranes. Essential oils from Zingiber cassumunar and Citrus hystrix have high lipophilicity and penetrate the stratum corneum, partially distributing in the epidermis and dermis. At the level of the skin barrier, they bind with lipid structures, providing prolonged local action and gradual release.

Flavonoid and phenolic compounds from Cuscuta reflexa are characterized by lower lipophilicity and limited transdermal permeability; with topical application, they are mainly concentrated in the superficial layers of the skin, providing local anti-inflammatory and antioxidant action. A part of these compounds may penetrate through mucous membranes and enter the systemic circulation in low concentrations.

Terpenes from Citrus hystrix undergo metabolism in the liver upon entering the systemic circulation, with the participation of cytochrome P450 system enzymes, leading to the formation of more hydrophilic metabolites. These products are predominantly excreted by the kidneys with urine, and also partially through bile. Phenylbutenoids from Zingiber cassumunar distribute in the skin and muscles, undergoing biotransformation in the liver via oxidation and conjugation with glucuronic acid.

The mineral component (calcium carbonate from cuttle bone) does not undergo biotransformation but performs a local buffering and adsorbing role. The entry of calcium into the systemic circulation with topical application is insignificant; its metabolism corresponds to the physiological pathways of calcium metabolism and renal excretion.

In general, the pharmacokinetics of the preparation are characterized by local action with limited systemic absorption, predominance of tissue-specific fixation of active substances in the skin and mucous membranes, and excretion through the kidneys and liver in case of systemic absorption.

References: PubMed (https://pubmed.ncbi.nlm.nih.gov)
PMC (https://pmc.ncbi.nlm.nih.gov)
ScienceDirect (https://www.sciencedirect.com)
SpringerLink (https://link.springer.com)

Mechanisms of Action and Scientific Rationale: Antifungal Spray

Liver and Gastrointestinal Tract. Phenylbutenoids from Zingiber cassumunar inhibit the activity of cyclooxygenase and lipoxygenase, reducing the production of pro-inflammatory prostaglandins and leukotrienes. Flavonoids from Cuscuta reflexa exhibit membrane-stabilizing and antioxidant action, reducing lipid peroxidation and supporting hepatocyte function. Terpenoids from Citrus hystrix enhance detoxification processes in the liver by activating phase II biotransformation enzymes, exerting a modulating effect on metabolic cascades.
References: PubMed (https://pubmed.ncbi.nlm.nih.gov), ScienceDirect (https://www.sciencedirect.com)

Immune System. Flavonoid compounds from Cuscuta reflexa exert a modulating influence on cytokine production (IL-1β, IL-6, TNF-α), reducing the level of pro-inflammatory mediators. Zingiber cassumunar activates macrophages and reduces NF-κB activity, leading to suppression of the inflammatory response. Terpenes from Citrus hystrix have an additive effect, influencing microbial cell membranes and increasing the efficiency of the immune response. The combined action of the components is characterized by a potentiating nature, with a predominant influence on the cellular level of immunoregulation.
References: SpringerLink (https://link.springer.com), Wiley Online Library (https://onlinelibrary.wiley.co...)

Nervous System. Phenylbutenoids from Zingiber cassumunar exhibit a mild analgesic and sedative effect by inhibiting inflammatory mediators and modulating MAPK signaling cascades. Flavonoids from Cuscuta reflexa act as antioxidants, protecting neurons from oxidative stress, and terpenoids from Citrus hystrix exert a modulating influence on neurotransmitter systems. The nature of the interaction is additive and modulating, with action levels at the cellular and tissue-specific levels.
References: PMC (https://pmc.ncbi.nlm.nih.gov), Semantic Scholar (https://www.semanticscholar.or...)

Endocrine and Metabolic Regulation. Flavonoids from Cuscuta reflexa and terpenes from Citrus hystrix exert antioxidant and metabolically modulating effects, reducing the activity of free radicals and regulating energy metabolism. Zingiber cassumunar exhibits lipotropic and membrane-stabilizing properties, influencing cell membranes and ion transport processes. These effects are modulating in nature and are realized at systemic and cellular levels, including JAK/STAT and NF-κB signaling cascades.
References: Taylor & Francis Online (https://www.tandfonline.com), WHO Monographs (https://apps.who.int)