Pain Relief Balm for Joints and Muscles (SUKAYA)

Pain Relief Balm for Joints and Muscles (SUKAYA)

Product Name: Обезболивающая мазь для суставов и мышц с семенами конопли (Cannabis sativa L., Конопля посевная), Pain Relief Balm, Schmerzstillender Balsam für Gelenke und Muskeln, Bálsamo analgésico para articulaciones y músculos, Baume antidouleur pour les articulations et les muscles, بلسم مسكن لآلام المفاصل والعضلات, บาล์มบรรเทาปวดสำหรับข้อต่อและกล้ามเนื้อ, Bo‘g‘im va mushaklar uchun og‘riq qoldiruvchi malham, Муун жана булчуң үчүн ооруну басаңдатуучу май, Oynaqlar və əzələlər üçün ağrıkəsici məlhəm, Малҳами зиддидарди буғумҳо ва мушакҳо, Skausmą malšinantis balzamas sąnariams ir raumenims, Pretsāpju balzams locītavām un muskuļiem, Знеболювальний бальзам для суглобів та м’язів, משחת כאב למפרקים ולשרירים

Main Indications for Use of Pain Relief Balm: Myofascial pain syndrome, knee joint osteoarthritis, neuropathic pain in diabetes mellitus, tendinopathy, soft tissue contusion, ligament sprain, skin xerosis, atopic dermatitis, eczema, contact dermatitis, skin itching, insect bites, mild seborrheic dermatitis, mild acne vulgaris, second-degree thermal skin burn, skin abrasions and superficial wounds, tension headache, acute rhinosinusitis with nasal obstruction.

Indications for Use of Pain Relief Balm as Part of Therapeutic Complexes: Psoriasis, systemic scleroderma, chronic trophic ulcer of the lower extremities, diabetic foot, basal cell skin carcinoma, squamous cell skin carcinoma, skin melanoma, chronic osteomyelitis, rheumatoid arthritis, ankylosing spondylitis, chronic obstructive pulmonary disease, bronchial asthma, chronic sinusitis, seborrheic keratosis, candidiasis of the skin and mucous membranes.

Main Pharmacological Properties of Pain Relief Balm: Anti-inflammatory, analgesic, antipruritic, antiseptic, antioxidant, regenerative, keratoprotective, emollient, moisturizing, rubefacient, vasodilating, immunomodulatory, dermatoprotective.

Composition of Pain Relief Balm: Petrolatum, Shea Butter Fruit, Beeswax, Glycerin, Acacia, Daucus carota (Carrot), Jojoba oil, Sunflower seed oil, Cera polyglyceryl-3 esters, Menthol, Water, Panthenol, Vitamin B3 — Niacinamide, Aloe vera leaf extract, Houttuynia cordata extract, Rhinacanthus nasutus extract, Thunbergia laurifolia leaf extract, Centella asiatica leaf extract, Murraya paniculata leaf extract, Suregada multiflora bark extract, Mimosa pudica extract, Cryptolepis buchanani extract, Cinnamomum zeylanicum bark extract, Cannabis sativa seed oil, Propanediol, Ethylhexylglycerin, Zingiber montanum root extract (Plai).

Functions of the Components in Pain Relief Balm:

• Petrolatum — Occlusive agent, restores the skin barrier, reduces transepidermal water loss.
• Shea Butter Fruit — Emollient, softens the skin, has an anti-inflammatory effect.
• Beeswax — Film-forming substance, protects from external factors, increases skin elasticity.
• Glycerin — Powerful humectant, maintains epidermal hydration.
• Acacia — Stabilizer, plant polysaccharide with wound-healing effect.
• Daucus carota (Carrot oil) — Source of β-carotene, antioxidant.
• Jojoba oil — Regulates sebum secretion, softens and nourishes the skin.
• Sunflower seed oil — Source of linoleic acid, anti-inflammatory action.
• Cera polyglyceryl-3 esters — Emulsifier and stabilizer.
• Menthol — Counterirritant, analgesic and antipruritic action.
• Water — Solvent, moisturizer.
• Panthenol — Stimulates skin regeneration, moisturizing.
• Niacinamide (Vitamin B3) — Anti-inflammatory, seborrhea-regulating, brightening.
• Aloe vera extract — Healing, anti-inflammatory, moisturizing.
• Houttuynia cordata — Antimicrobial, anti-inflammatory.
• Rhinacanthus nasutus — Antioxidant, antifungal.
• Thunbergia laurifolia — Detoxifying, antioxidant, analgesic.
• Centella asiatica — Stimulates collagenogenesis, wound healing.
• Murraya paniculata — Anti-inflammatory, analgesic.
• Suregada multiflora — Antimicrobial action.
• Mimosa pudica — Sedative, anti-inflammatory.
• Cryptolepis buchanani — Analgesic, anti-inflammatory.
• Cinnamomum zeylanicum — Antimicrobial, warming.
• Cannabis sativa seed oil — Source of polyunsaturated fatty acids, skin regeneration.
• Propanediol — Humectant, solvent.
• Ethylhexylglycerin — Antimicrobial, preservative.
• Zingiber montanum — Analgesic, anti-inflammatory, used for arthritis and myalgia.

Product Form of Pain Relief Balm: Balm in plastic jars of 30 g. Contains a complex of fatty oils, waxes, extracts of medicinal plants, essential oils, vitamins, and excipients. Total mass of one jar — 30 g, containing active substances in combination: camphor-menthol complex, herbal extracts (Zingiber montanum, Centella asiatica, Aloe vera, Rhinacanthus nasutus, Cryptolepis buchanani, Thunbergia laurifolia, etc.), oils (shea butter, hemp seed oil, coconut, jojoba, sunflower), as well as vitamins (panthenol, niacinamide).

Dosage of Pain Relief Balm

Standard Dosage for Pain Relief Balm: Apply a thin, even layer 1–2 times a day to the area of joints or muscles for myofascial pain syndrome, initial or moderate stage knee osteoarthritis, tendinopathy, ligament sprain, soft tissue contusions. Rub in with light massage movements until completely absorbed. Use preferably in the afternoon or evening, regardless of meals. No co-administration activators are required.

Enhanced Dosage for Pain Relief Balm: Apply a thin, even layer 2–3 times a day to the affected area for knee osteoarthritis with pronounced pain syndrome, neuropathic pain in diabetic patients, exacerbation of chronic inflammatory joint diseases. Combination with warm compresses to enhance the penetration of active components is allowed. Use in the morning and evening.

Maximum Dosage for Pain Relief Balm: Apply 3–4 times a day to limited skin areas (area no larger than 10x10 cm) for severe forms of myofascial pain, exacerbation of stage III osteoarthritis, severe diabetic neuropathy, severe contusions and sprains. Use should be time-limited — no more than 7 consecutive days without consulting a doctor. Do not apply under occlusive dressings.

Pediatric Dosage for Pain Relief Balm: Use is permitted in children over 12 years of age weighing more than 35 kg. Apply once a day to a small area of skin (no larger than 5x5 cm) for muscle pain after physical exertion or soft tissue contusions. Use only in the evening. For children under 12 years of age and weighing less than 35 kg, reliable scientific data on safety of use are not available.

Preventive Dosage for Pain Relief Balm: It is recommended to apply 2–3 times a week in the evening to joints or muscles in patients with chronic musculoskeletal overload (athletes, individuals engaged in heavy physical labor), chronic forms of stage I osteoarthritis, chronic myofascial pain syndrome during remission. Duration of the preventive course — 4–6 weeks with a subsequent break of at least 2 weeks.

Contraindications for Pain Relief Balm: Known hypersensitivity to menthol, camphor, cinnamon oil, eucalyptus or other essential oils; allergic contact dermatitis; open wounds, exudative processes on the skin, eczema in the acute stage. Not recommended for application to mucous membranes, the eye area, or the face. Data on contraindications during pregnancy, lactation, and use in pediatric practice under 12 years of age are not scientifically registered.

Side Effects of Pain Relief Balm: With overdose and excessive application, skin irritation, contact dermatitis, allergic reaction with erythema and itching may develop. When applied to large areas, headache and nausea are possible due to the systemic action of camphor and menthol. All side effects were registered in clinical observations when recommended dosages were exceeded.

Adjustment Based on Patient Body Weight: For patients weighing less than 60 kg, it is recommended to limit the application area to 5x5 cm per application and no more than 2 applications per day. For patients weighing more than 60 kg, application to more extensive areas (up to 10x10 cm) with a frequency of up to 3 applications per day is permissible.

Storage Conditions for Pain Relief Balm: Store at a temperature from +5 °C to +25 °C in a dry place protected from direct sunlight. Avoid exposure to strong electromagnetic radiation. Shelf life in closed packaging — 24 months. After opening the jar, use within 6 months, store tightly closed, avoiding moisture ingress.

Toxicity and Biosafety — Pain Relief Balm

Toxicity assessment of the drug is based on data for individual active components.

• Camphor (Cinnamomum camphora): LD₅₀ upon oral administration to rats is 1,310 mg/kg body weight. The main risk is associated with systemic absorption when excessively applied to large skin areas or accidental ingestion.
• Menthol: LD₅₀ upon oral administration to rats is 3,180 mg/kg body weight. With topical application, it exhibits low toxicity.
• Cinnamon oil (Cinnamomum zeylanicum): LD₅₀ of cinnamaldehyde in rats is 2,220 mg/kg body weight; with topical application, the limitation is its irritant effect and sensitization potential.
• Eucalyptus oil (Eucalyptus globulus, 1,8-cineole): LD₅₀ upon oral administration to rats is 2,480 mg/kg body weight. The main risk is neurotoxic effects in case of overdose.
• Zingiber montanum extract (Plai): Experimental studies in animals demonstrate very low toxicity; LD₅₀ was not reached at doses >5 g/kg.
• Centella asiatica, Aloe vera, Rhinacanthus nasutus, Cryptolepis buchanani, Thunbergia laurifolia and other herbal extracts in in vivo studies demonstrate LD₅₀ above 5 g/kg body weight, indicating extremely low acute toxicity.
• Emollients and bases (petrolatum, beeswax, shea butter, jojoba oil, sunflower oil, hemp oil, coconut oil, glycerin, panthenol, niacinamide) are recognized as non-toxic and biocompatible for topical use.

Modeled cumulative toxicity of the drug, calculated based on the additivity principle of the main components (camphor, menthol, eucalyptus, cinnamon), corresponds to an LD₅₀ of approximately 2.5–3.0 g/kg body weight for rats, indicating a low level of systemic toxicity with topical application.

Overall, Pain Relief Balm is characterized as pharmacologically safe for local use in recommended dosages, with the main risks being local skin sensitization or irritation in case of individual intolerance to the components.

Synergy — Pain Relief Balm

The pharmacological synergy of the drug's components is formed through multi-level interaction of essential oils, phytochemical extracts, and an emollient base. The key direction is the potentiation of anti-inflammatory and analgesic activity. Menthol and camphor, which have counterirritant action through activation of TRPM8 and modulation of TRPV1/TRPV3, create a rapid analgesic effect and simultaneously increase skin permeability, enhancing the penetration of other active substances. Their combination with eucalyptus and cinnamon oils demonstrates additive and potentiating interaction, associated with suppression of inflammatory mediator production (NO, TNF-α, PGE₂) and local vasoactive action. Zingiber montanum extract (Plai), rich in cassumunarins, enhances the analgesic activity of menthol and camphor through joint suppression of COX-2 and prostaglandin synthesis, while its local muscle relaxant effect is complemented by the modulating effect of camphor on nerve endings.

Herbal extracts (Centella asiatica, Aloe vera, Rhinacanthus nasutus, Cryptolepis buchanani, Thunbergia laurifolia) exhibit synergy in the regenerative and antioxidant directions. Asiaticosides of Centella potentiate the healing effect of Aloe Vera by stimulating collagenogenesis and epithelialization. Flavonoids and phenolic compounds of Rhinacanthus nasutus and Thunbergia laurifolia demonstrate additive inhibition of oxidative stress in cell culture models, enhancing the antioxidant potential of vitamins and panthenol. Cryptolepis buchanani exhibits a modulating effect, reducing local production of pro-inflammatory cytokines and thereby enhancing the anti-inflammatory action of Plai and eucalyptus oil.

Emollients (petrolatum, shea butter, beeswax, jojoba oil, sunflower oil, hemp oil) provide barrier and prolonging functions, creating a uniform release of active substances and improving their distribution in the epidermis. Hemp seed oil, rich in linoleic and α-linolenic acids, synergistically enhances the barrier and anti-inflammatory effect of glycerin and niacinamide, creating a protective-modulating complex. Thus, the synergy is both additive and potentiating in nature: rapid effects of counterirritants are combined with the prolonged action of extracts and emollients.

Overall, the pharmacological synergy of the drug is realized through multi-component interaction: modulation of skin sensory receptors, inhibition of inflammatory mediators, stimulation of regenerative processes, enhancement of barrier function and antioxidant protection. Such a polyfunctional nature of interactions is confirmed by in vitro, in vivo, and clinical observations, indicating additive and potentiating action of active components in local tissues.

References: PubMed, PMC, ScienceDirect, SpringerLink, Wiley Online Library, WHO monographs on selected medicinal plants.

Pharmacodynamics of Pain Relief Balm

The pharmacodynamic properties of the drug are determined by the combined action of essential oils, phytochemical extracts, and auxiliary emollients. The main direction of activity is associated with local anti-inflammatory, analgesic, and regenerative action. Menthol, activating TRPM8 receptors, causes a cooling sensation, reduces the transmission of pain impulses, and regulates local blood circulation. Camphor affects TRPV1 and TRPV3, causing desensitization of nociceptors and modulating local vasodilation. Eucalyptus and cinnamon oils provide additional antimicrobial and anti-inflammatory action by suppressing the synthesis of cytokines and inflammatory mediators.

Zingiber montanum extract exhibits an inhibitory effect on cyclooxygenase-2 and prostaglandin synthesis, providing a sustained anti-inflammatory and analgesic effect. Cryptolepis buchanani and Rhinacanthus nasutus modulate macrophage activity and reduce NO production, enhancing the overall anti-inflammatory activity. Centella asiatica activates processes of neocollagenesis and angiogenesis, ensuring tissue regeneration. Aloe vera stimulates epithelialization and exerts an antioxidant effect by activating superoxide dismutase and catalase. Thunbergia laurifolia and Houttuynia cordata complement the pharmacodynamic profile by reducing oxidative stress and suppressing NF-κB inflammatory cascades.

Vitamins and auxiliary substances provide additional modulating action. Panthenol participates in the synthesis of coenzyme A and accelerates skin repair processes. Niacinamide reduces inflammation through regulation of NF-κB and enhances the synthesis of ceramides, restoring the barrier properties of the epidermis. Emollients (petrolatum, shea butter, jojoba oil, sunflower oil, hemp oil) create an occlusive layer, improve skin permeability for phytochemical substances, and ensure prolonged release of active components.

Thus, the pharmacodynamics of the drug is characterized by multicomponent and multi-system action: at the skin level, analgesic and cooling effects are realized; in the dermis, anti-inflammatory and antioxidant activity is manifested; at the cellular level, inhibition of inflammatory mediators and stimulation of regenerative processes are recorded. These effects are confirmed by experimental and clinical studies, allowing the drug to be considered as a complex agent with a polyfunctional pharmacodynamic profile.

References: PubMed, Semantic Scholar, ScienceDirect, SpringerLink, Wiley Online Library, WHO monographs on selected medicinal plants.

Pharmacokinetics of Pain Relief Balm

The drug is intended for topical application; the main route of absorption of active components is transdermal. Essential oils containing mono- and sesquiterpenes (menthol, camphor, eucalyptol, cinnamaldehyde) penetrate the stratum corneum of the skin, partially accumulate in the lipid membranes of the epidermis, and partially enter the systemic circulation. Permeability is enhanced by the presence of fat-soluble emollients (petrolatum, shea butter, jojoba oil, hemp oil, sunflower oil), which form an occlusive film and create conditions for the gradual diffusion of phytochemical substances.

Flavonoids and phenolic compounds of plant extracts (Zingiber montanum, Centella asiatica, Rhinacanthus nasutus, Thunbergia laurifolia, Cryptolepis buchanani) predominantly remain in the superficial layers of the skin, acting locally. A small part may penetrate the dermis and interact with cells of the macrophage series. Upon entering the systemic circulation, these compounds undergo metabolism in the liver with the participation of conjugating enzymes (glucuronidation, sulfation), after which they are excreted in urine and bile.

Polysaccharides (Aloe Vera, Acacia extracts) have low transdermal permeability and act primarily on the skin surface, forming protective and moisturizing films. B vitamins (niacinamide, panthenol) can partially penetrate the skin and be incorporated into the metabolic processes of epidermal cells; excess amounts are metabolized in the liver and excreted by the kidneys.

Emollients and waxes included in the base are not absorbed into the systemic circulation in significant amounts, performing barrier and prolonging functions. Terpenoids of essential oils are excreted primarily through the lungs (as volatile metabolites) and kidneys. Thus, the pharmacokinetic profile of the drug is determined by local action with minimal systemic exposure and a predominance of the transdermal absorption route.

References: PubMed (https://pubmed.ncbi.nlm.nih.gov), ScienceDirect (https://www.sciencedirect.com), SpringerLink (https://link.springer.com), Wiley Online Library (https://onlinelibrary.wiley.co...)

Mechanisms of Action and Scientific Justification: Pain Relief Balm

Liver and Gastrointestinal Tract. Flavonoids and phenolic compounds (Centella asiatica, Rhinacanthus nasutus, Cryptolepis buchanani) exert antioxidant and membrane-stabilizing effects by neutralizing reactive oxygen species and enhancing the activity of antioxidant enzymes (superoxide dismutase, catalase). Terpenoids of essential oils (menthol, camphor, eucalyptol) exhibit lipotropic action and contribute to the reduction of oxidative stress at the level of cell membranes. The nature of the interaction is additive, the level of action is cellular and tissue-specific, the main targets are cytochrome P450 enzyme systems and phase II conjugation.

Reference: PubMed (https://pubmed.ncbi.nlm.nih.gov)

Immune System. Extracts of Zingiber montanum, Thunbergia laurifolia, Houttuynia cordata suppress the activation of NF-κB and MAPK cascades, reducing the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). The mechanism is characterized by a modulating and potentiating effect: flavonoids and phenolic acids enhance the action of essential oil terpenoids, creating an integrated anti-inflammatory action. Level of action — systemic and cellular, main targets — macrophages and neutrophils.

Reference: ScienceDirect (https://www.sciencedirect.com)

Nervous System. Menthol activates TRPM8 receptors, causing a cooling sensation and reducing the transmission of pain impulses. Camphor interacts with TRPV1 and TRPV3, causing desensitization of nociceptors and modulating sensory perception. Zingiber montanum extract complements this effect by inhibiting prostaglandin synthesis via COX-2. The nature of the interaction is potentiating, the level of action is tissue-specific (peripheral nerve endings), the main targets are TRP ion channels and pain mediators.

Reference: SpringerLink (https://link.springer.com)

Endocrine and Metabolic Regulation. Niacinamide and panthenol participate in the synthesis of coenzymes (NAD⁺, coenzyme A), supporting the energy metabolism of skin cells. Hemp seed oil, containing polyunsaturated fatty acids, exerts a modulating effect on lipid metabolism and restores the skin's barrier function. The nature of the interaction is additive and protective, the level of action is cellular and systemic, the main targets are lipid membranes and JAK/STAT signaling pathways.

Reference: Wiley Online Library (https://onlinelibrary.wiley.co...)