Description:Title of the Invention
Pain relieving topical composition.
Field of the Invention
The present invention relates generally to topical compositions for pain relief. More particularly, the present invention relates to topical compositions comprising at least one cannabinoid, natural analgesics such as TRPM8 agonists, TRPA1 antagonists, TRPV1 agonists, COX-2 inhibitors or combination thereof, and one or more muscle spasmodic inhibitors.
Background of the invention
Pain is a distressing localized or generalized unpleasant sensation that can be stimulated by intense or damaging stimuli, causes mild to severe physical discomfort, emotional distress and specifically results from physical ailments. It may be acute or chronic, and can trigger people of any gender, age, and ethnicity deprived of warning. Pain management is an essential part of healthcare and a fundamental human right. Pain management strategies comprise pain relieving medicines (safe or hazardous), physical and complementary treatments (such as acupuncture and massage).
In general individuals frequently rely on over-the-counter medications such as non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for short-term relief, often assuming they are safe because of their widespread accessibility. However, prolonged use of painkillers can lead to impairment to organs, connective tissues, ulcers, and the development of tolerance. When these medications lose their effectiveness, many individuals seek stronger alternatives, such as opioids, which are highly addictive, can lead to rapid dependence, and frequently result in fatal consequences. Such patients, particularly the elderly, have little option but to suffer from chronic pain or seek non-traditional treatment modalities.
Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. Inhibition of pain in the skin disrupts the pain cycle and avoids exposure of internal organs to large amounts of toxic compounds. But topical administration of conventional NSAIDS has largely been ineffective because only a therapeutically ineffective amount of the drug can penetrate the skin. In addition, indications such as acne, psoriasis and eczema are typically refractory to topical or oral administration of NSAIDS.
Moreover, many products available include expensive ingredients, require frequent applications and provide relief of pain for only short periods. Many products that provide pain relief do not enhance recovery. Therefore, preference for herbal medicines is increasing day by day and there is a growing desire to eliminate contact with harmful synthetic materials in the treatment of pain disorders and inflammation.
Numerous pain relief compositions in the form of creams, ointments, and lotions with natural analgesic ingredients like cannabinoids, camphor, menthol, methyl salicylate, capsaicin etc., have been developed and are commercially available for treatment and relief of minor aches or soreness. Topical pain relief formulation featuring essential and cold pressed oils, extracts, compounds of herbs are used worldwide against different types of pain owing to their safety and efficacy aspects. Despite their use, many existing products are limited by irritation or burning caused by high-dose capsaicin, lack of synergistic mechanisms, often targeting only nociceptors or vasodilation, unstandardized phytochemical content, particularly in herbal preparations, suboptimal transdermal absorption due to inadequate carrier systems.
US6589543B1 discloses a topical pain relief gel containing capsaicin, clove oil, ginger root powder, wintergreen and peppermint oils, and a base of petroleum jelly for providing pain relief and anti-inflammatory action. The formulation limits the permeation enhancers, encapsulation (e.g., nanocarriers), or controlled-release technology that could improve penetration or tolerability.
US2008/0145461A1 discloses a topical pain relief composition for applying to the skin, comprising a mixture of stearic acid, emulsifying polymer, arnica oil, peppermint oil, and distilled water. The patent doesn't clearly elucidate synergistic interactions between different ingredients. Further, ingredients like stearic acid form waxy or occlusive barriers, potentially limiting bioavailability of arnica or peppermint actives. It may reduce user compliance in warm/humid climates.
US5560910A discloses a topical anti-inflammatory composition containing bromelain, capsaicin and a penetrating agent selected from n-decylmethyl sulfoxide and lecithin organo gel. Penetration enhancers like n-decylmethyl sulfoxide, a derivative of DMSO, may cause skin dryness, peeling, or dermatitis. There are chances of systemic absorption of unwanted substances, since sulfoxides can carry other chemicals through the skin. Bromelain, though anti-inflammatory, may cause hypersensitivity or local allergic reactions, particularly in sensitive individuals or those with pineapple allergies.
WO2015061847A1 discloses a topically administrable pain relief formulation comprises a Kunzea ambigua extract, menthol, capsaicin; and a Hypericum perforatum, methyl salicylate, black pepper and an anti-inflammatory agent to treat or prevent pain such as arthritis neck pain, shoulder pain, back pain, preoperative and/or postoperative pain and pain associated with minor or traumatic injuries or other diseases or conditions. The claimed invention targets cannabinoid-related pathways but does not engage multi-pathway mechanisms (e.g., TRP ion channel modulation, COX-2 inhibition)
EP3388057A1 discloses a TRPV1 selective agonist topical compositions including capsaicinoid and analgesic agent compositions and methods of manufacture and methods of providing pain relief as well as treating a variety of disorders with such compositions. It focuses on capsaicin monotherapy, lacks synergy with ECS, low-dose optimization, or herbal counter-irritants.
Classical Ayurvedic oils (e.g., Mahanarayana Taila, Narayana Taila) are composed of multiple herbs in sesame oil base and used for musculoskeletal conditions. These Ayurvedic oils do not contain capsaicin, phyto-cannabinoids, or synthetic standards, have poor dermal absorption.
US2023/025693A1 discloses CBG/CBD transdermal gel with nano/micro-emulsion and synergistic terpenes for musculoskeletal inflammation relief, mainly emphasizes on deep tissue delivery and improved pharmacokinetics, but lacks synergistic natural counterirritants.
US20120264818 discloses topical compositions including heat-treating mature, dried, powdered cannabis sativa flower and bud leaves in carriers and methods for the treatment of pain and methicillin-resistant Staphylococcus aureus. The formulation does not incorporate non-cannabinoid, standardized anti-inflammatory agents that could enhance therapeutic outcomes.
The effective pain management for different conditions such as chronic pain, neuropathic pain, and inflammation requires the optimal and synergistic modulation of different intracellular signalling pathways dependent on activation and/or deactivation of a variety of receptors for example CB1 and CB2 receptors of endocannabinoid system, TRP ion channels including TRPM8, TRPA1 and TRPV1 and other systems involved in perception and signalling of the pain. For example, for effective pain relief compositions should have analgesic agents which activate TRPM8 (i.e., desirable cooling, reducing pain and/or anti-inflammatory properties) and inhibit TRPAl (i.e., undesirable causation of cold pain and inflammation).
Though, a number of different pain relief compositions exist, but they lack the optimal and synergistic modulation of different intracellular signalling pathways involved in perception and signalling of the pain leading to effective pain relief.
Therefore, topical pain relief compositions are required which provide pain relief by acting on multiple pathways involved in perception and signalling of the pain, with enhanced dermal absorption and minimum irritation.
Further, topical pain relief compositions are required which provide optimal and synergistic modulation of different intracellular signalling pathways dependent on activation and/or deactivation of a variety of receptors including CB1 and CB2 receptors of endocannabinoid system, TRP ion channels and other systems involved in perception and signalling of the pain.

Summary of the invention
In various aspects and embodiments, the present invention provides a topical pain-relieving composition comprising at least one cannabinoid; at least one analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof; and at least one muscle spasmodic inhibitor. In another aspect topical pain-relieving composition further comprises a carrier, and optionally a NSAID.
In various aspects and embodiments, the present invention provides a topical pain-relieving composition comprising at least one phyto-cannabinoid; at least one natural analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof; and at least one muscle spasmodic inhibitor, wherein composition further comprises a carrier, and optionally a NSAID.
In an embodiment, the formulation is designed for easy and non-invasive topical application, exhibits rapid dermal absorption, and provides potent analgesic and anti-inflammatory effects. It is particularly effective in the treatment of acute pain, chronic musculoskeletal pain, neuropathic pain, and supports tissue healing through a multi-mechanistic pharmacological approach. The muti-mechanism approach involving modulation of CB1 and CB2 receptors, control of TRP ion channels and inhibition of enzyme cyclo-oxygenase-2 (COX-2) is the basis for formulating the topical pain relief compositions of the present invention.
The present invention provides a topical pain-relieving composition comprising: a) at least one cannabinoid(s); b) natural analgesic agents selected from TRPM8 agonists, TRPA1 antagonists, TRPV1 agonists, COX-2 inhibitors or combination thereof; and c) at least one muscle spasmodic inhibitor.
In an embodiment, the composition comprises essential oil, extract, oil of various plants as a source of phytocannabinoids, TRPM8 agonists, TRPA1 antagonists, TRPV1 agonists, COX-2 inhibitors and muscle spasmodic inhibitors. These compositions are effective in pain relief by providing optimal and synergistic modulation of different intracellular signalling pathways dependent on activation and/or deactivation of a variety of receptors including CB1 and CB2 receptors of endocannabinoid system, TRP ion channels and other systems involved in perception and signalling of the pain.
In an embodiment, the cannabinoid comprises two or more phyto-cannabinoids present in the extract of Cannabis plant selected from Cannabis sativa, Cannabis indica or Cannabis ruderalis.
In an embodiment, the phyto-cannabinoids are selected from tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), Cannabigerolic acid monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT) or a combination thereof.
In an embodiment, the topical pain-relieving composition comprises:
a) 1% to 30% w/w of Cannabis plant extract;
b) 0.1% to 10% w/w of TRPA1 antagonist;
c) 1% to 10% w/w of TRPM8 agonist;
d) 1% to 10% w/w of COX-2 inhibitor;
e) 0.01% to 1.0% w/w of TRPV1 agonist;
f) 1% to 40% w/w of muscle spasmodic inhibitor; and
g) 1% to 90% w/w of carrier.
In an embodiment, TRPA1 antagonist comprises essential oil of plants selected from Eucalyptus species comprising Eucalyptus polybractea, Eucalyptus globulus, Eucalyptus smithii, Eucalyptus radiate or Eucalyptus camaldulensis; Rosmarinus species comprising Rosmarinus officinalis; Salvia species comprising Salvia officinalis or Salvia lavandulifolia; Thymus satureioides; Cinnamomum camphora or Cinnamomum burmanni.
In another embodiment, the TRPM8 agonist is selected from menthol, eucalyptol, borneol, rotundifolone, linalool, menthone, geraniol, isopulegol or a combination thereof.
In an embodiment, COX-2 inhibitor comprises essential oil of plants selected from Wintergreen (Gaultheria procumbens) or sweet birch (Betula lenta).
In an embodiment, TRPV1 agonist is selected from capsaicin, resiniferatoxin or hirsuteine.
In an embodiment, the muscle spasmodic inhibitor is selected from an oil of Arnica montana, Foeniculum vulgare or Zingiber officinale.
In an embodiment, the composition optionally comprises a non-steroidal anti-inflammatory agent selected from benzydamine, indomethacin, arthrotec, celecoxib, diclofenac, rofecoxib, vadecoxib, naproxen, ibuprofen, piroxicam, ketoprofen, felbinac, or a combination thereof.
In an embodiment, the composition comprises one or more carriers and/or excipients.
In an embodiment, the carrier is an oil selected from the group consisting of grape seed oil, medium-chain triglycerides oil, olive oil, coconut oil, sesame oil, jojoba oil, rosehip oil, palm oil, flaxseed oil, hemp seed oil, chamomile oil, cinnamon oil, citron oil, nutmeg oil, oregano oil, orris oil, palo santo oil, parsley oil, peppermint oil or a combination thereof.
In an embodiment, the topical pain-relieving composition comprises:
a) 1% to 30% w/w of Cannabis plant extract;
b) 0.1% to 10% w/w of essential oil of plants selected from Eucalyptus, Rosmarinus, Salvia, Thymus satureioides, Cinnamomum camphora or Cinnamomum burmanni;
c) 1% to 10% w/w of menthol, eucalyptol, borneol, rotundifolone, linalool, menthone, geraniol, isopulegol or a combination thereof;
d) 1% to 10% w/w essential oil of plants selected from Wintergreen (Gaultheria procumbens) or sweet birch (Betula lenta);
e) 0.01% to 1.0% w/w of capsaicin, resiniferatoxin or hirsuteine;
f) 1% to 40% w/w of oil of plants selected from Arnica (Arnica montana), Fennel (Foeniculum vulgare) or Ginger (Zingiber officinale); and
g) 1% to 90% w/w of carrier selected from the group consisting of grape seed oil, medium-chain triglycerides oil, olive oil, coconut oil, sesame oil, jojoba oil, rosehip oil, palm oil, flaxseed oil, hemp seed oil, chamomile oil, cinnamon oil, citron oil, nutmeg oil, oregano oil, orris oil, palo santo oil, parsley oil, peppermint oil or a combination thereof.
In an embodiment, the composition may include one or more excipients selected from, but are not limited to, thickeners, emollients, humectants, surfactants, colorants, preservatives, stabilizers or a combination thereof.
In an embodiment, the topical pain-relieving composition is in the form of an oil, cream, lotion, ointment, paste, gel, suspension, spray, pump spray, aerosol spray, non-pressurized spray, continuous spray, aerosol foam, liquid, mousse or solution, preferably oil.
Additional aspects, advantages, features, and objects of the present disclosure would be made apparent from the detailed description of the illustrative embodiments, construed in conjunction with the appended claims.
It will be appreciated that the features of the present disclosure are susceptible to being combined in various combinations without departing from the spirit and the scope of the disclosure, as defined by the appended claims.

Detailed Description of the Invention
The following detailed description illustrates embodiments of the present disclosure and ways in which they can be implemented. This description is not intended to be a detailed log of all the possible ways in which the invention may be implemented, or all features that may be added to the instant invention. For example, features illustrated with respect to a particular embodiment may be incorporated into other embodiment, and features illustrated with respect to a particular embodiment may be deleted from that embodiment. In addition, numerous variations and additions to the various embodiment suggested herein will be apparent to those skilled in the art in light of the present disclosure, which do not depart from the present invention. Although some modes of carrying out the present disclosure have been disclosed, those skilled in the art would recognize that other embodiments for carrying out or practicing the present disclosure are also possible.
The use of “comprise”, “comprises”, “comprising”, “contain”, “contains”, “containing”, “include”, “includes”, and “including” are not intended to be limiting. It is to be understood that both the foregoing general description and this detailed description are exemplary and explanatory only and are not restrictive.
Expressions such as “comprise” and “include”, and variations such as “comprises”, “comprising”, “includes”, and including are intended to be construed in a non-exclusive manner, namely allowing for items, components, or elements not explicitly described (or recited) also to be present. Reference to the singular is also to be construed to relate to the plural, except where explicitly stated.
Unless otherwise defined, scientific and technical terms and symbols used herein shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.
For clarity, certain terms used in the specification are defined and presented as follows.
The term “plant” refers to all physical parts of a plant, including shoots, leaves, flowers, needles, stalks, stems, fruit bodies, fruits, seeds, roots, tubers and rhizomes. The term “w/w” refers to weight by weight. The term “w/w” refers to weight by weight of, for example a composition or a formulation or a combination.
In various aspects and embodiments, the present invention provides a topical pain-relieving composition comprising at least one cannabinoid; at least one analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof; and at least one muscle spasmodic inhibitor.
In another aspect topical pain-relieving composition further comprises a carrier, and optionally a NSAID.
In various aspects and embodiments, the present invention provides a topical pain-relieving composition comprising at least one phyto-cannabinoid; at least one natural analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof; and at least one muscle spasmodic inhibitor, wherein composition further comprises a carrier, and optionally a NSAID.
The perception and signalling of the pain in response to various external and internal stimuli including chemical, mechanical or thermal stimuli is a complex physiological process, which involves various intracellular signalling pathways dependent on activation and/or deactivation of a variety of receptors. Further, inflammation can also alter the sensitivity of nociceptors, making them more likely to fire pain signals even in response to stimuli that would not normally cause pain (peripheral sensitization). When inflammation persists over a longer period, it can lead to chronic pain. The effective pain management for different conditions such as chronic pain, neuropathic pain, and inflammation, can be achieved by stimulation and/or inhibition of receptors (CB1 and CB2 receptors of endocannabinoid system (ECS)), TRP ion channels including TRPM8, TRPA1 and TRPV1, desensitization of peripheral nociceptors and inhibit the formation of various inflammatory mediators such as prostaglandins.
Some TRP ion channels for example TRPM8 can be activated to decrease or eliminate the sensing of pain. Some TRP ion channels for example TRPA1 and TRPV1 can be inhibited to decrease or eliminate the sensing of pain.
Surprisingly, the inventors of the present application found that when a cannabinoid is combined with a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist and a COX-2 inhibitor in an effective amount, it provides an effective pain relief and reduce inflammation associated with different conditions and also supports tissue healing.
In an embodiment, the formulation is designed for easy and non-invasive topical application, exhibits rapid dermal absorption, and provides potent analgesic and anti-inflammatory effects. It is particularly effective in the treatment of acute pain, chronic musculoskeletal pain, neuropathic pain, and supports tissue healing through a multi-mechanistic pharmacological approach. The muti-mechanism approach involving modulation of CB1 and CB2 receptors, control of TRP ion channels and inhibition of enzyme cyclo-oxygenase-2 (COX-2) is the basis for formulating the topical pain relief compositions of the present invention.
In one aspect, the present invention provides a topical pain relieving composition comprising cannabinoid which may be a phyto-cannabinoid or synthetic cannabinoid, natural analgesic agent TRPA1 antagonist and analgesic agent TRPM8 agonist present in essential oil of plants selected from Eucalyptus, Rosmarinus, Salvia, Thymus satureioides, Cinnamomum camphora or Cinnamomum burmanni, analgesic agent; natural TRPM8 agonist including menthol, eucalyptol, borneol, rotundifolone, linalool, menthone, geraniol, or isopulegol; natural analgesic agent COX-2 inhibitor present in essential oil of plants selected from Wintergreen (Gaultheria procumbens) or sweet birch (Betula lenta); natural analgesic agent TRPV1 agonist including Capsaicin, Resiniferatoxin or hirsuteine; natural muscle spasmodic inhibitor selected from an oil of Arnica montana, Foeniculum vulgare or Zingiber officinale.
In an embodiment, the present invention provides a topical pain-relieving composition comprising cannabinoid which may be a phytocannabinoid or synthetic cannabinoid, Eucalyptus essential oil as TRPA1 antagonist and TRPM8 agonist, menthol as TRPM8 agonist, Wintergreen essential oil as COX-2 inhibitor, Capsaicin as TRPV1 agonist, Arnica montana oil as muscle spasmodic inhibitor and optionally a carrier.
In an embodiment, the present invention provides a topical pain-relieving composition comprising Cannabis plant extract as a source of phyto-cannabinoids, Eucalyptus essential oil as TRPA1 antagonist and TRPM8 agonist, menthol as TRPM8 agonist, Wintergreen essential oil as COX-2 inhibitor, Capsaicin as TRPV1 agonist, Arnica montana oil as muscle spasmodic inhibitor and optionally a carrier.
In an embodiment, the topical pain relieving composition of the present invention is unexpectedly effective as a result of the synergy of cannabinoids, preferably phytocannabinoids with TRPA1 antagonist and TRPM8 agonist and TRPV1 agonist such as Capsaicin: synergy of COX-2 inhibitor such as methyl salicylate present in Wintergreen essential oil with TRPA1 antagonists and TRPM8 agonists, wherein TRPA1 antagonists inactivate the gating of the TRPA1 ion channel associated with methyl salicylate.
This unique formulation acts via multiple pharmacological pathways including the endocannabinoid system (ECS), TRPV1 (capsaicin) and TRPM8 (menthol) ion channels, peripheral vasodilation (methyl salicylate), and inflammatory cytokine modulation (A. montana) to provide effective pain relief without systemic side effects.
In an embodiment, the cannabinoids include, but not limited to, tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), Cannabigerolic acid monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT) or any combination thereof.
In an embodiment, the above listed cannabinoids are phyto-cannabinoids, obtained from a plant. The phyto-cannabinoids may be obtained from plant extract. In an embodiment, the phyto-cannabinoids are obtained from the extract of plant Cannabis of the family Cannabaceae.
The endocannabinoid system (ECS), comprising cannabinoid 1 (CB1) and 2 (CB2) receptors, endogenous ligands (anandamide and 2-arachidonoylglycerol (2-AG)), and associated metabolic enzymes, plays a crucial role in modulating pain perception, inflammation, and neuroimmune interactions. Phytocannabinoids from Cannabis sativa, particularly cannabidiol (CBD), cannabigerol (CBG), and low levels of Δ9-tetrahydrocannabinol (THC), have demonstrated analgesic effects through CB2 receptor activation and indirect TRPV1 modulation, among other mechanisms.
In parallel, TRP ion channels-especially TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (menthol receptor) mediate sensory neuron depolarization and pain signaling. Capsaicin, a known TRPV1 agonist, promotes desensitization of peripheral nociceptors through depletion of substance P, while menthol, acting on TRPM8, produces a cooling sensation that competes with pain signals at the central processing level. Furthermore, methyl salicylate from wintergreen oil acts as a counterirritant and vasodilator, increasing local circulation and reducing muscle stiffness.
In an embodiment, the composition comprises extract of plant Cannabis of the family Cannabaceae as a source of phytocannabinoids. The extract may be obtained from the species Cannabis sativa, Cannabis indica, and Cannabis ruderalis which vary in their biochemical constituents. In a preferred embodiment the extract is be obtained from Cannabis sativa. The plant part used for the extraction is more preferably leaves. As used here in the term “extract” refers to a composition or preparation comprising one or more active compounds, components or substance extracted, isolated from a particular source. The active compounds, components or substance in the extract may be in a more concentrated or enriched form compared to the source. Phytocannabinoids from C. sativa are bioactive terpenoids which exert their biological effects by mimicking the actions of endocannabinoids (family of endogenous bioactive mediators) and activate two specific G protein-coupled cannabinoid receptors: CB1 and CB2.
C. sativa has long been utilized by human populations across the world for its therapeutic properties, from pain relief to treatment of epilepsy. Cannabis sativa is an annual herbaceous flowering plant belonging to the family Cannabaceae family. Cannabinoids (active components of C. sativa), are effective against depression, migraine, multiple sclerosis, fibromyalgia, syndromes like Parkinson and Gilles de la Tourette and relieve (chronic neurogenic/neuropathic) pain. Additionally, it is also used as an analgesic, spasmolytic, appetite stimulation, and a palliative and anti-convulsant medication. Raw cannabis has a variety of health benefits, in particular cannabinoid acids found in plant material are potent anti-inflammatory agents.
Decarboxylation of the naturally occurring cannabinoid acids, typically by heating, increases their bioavailability. In some instances, the decarboxylation process converts a non-psychoactive cannabinoid acid into a psychoactive cannabinoid. For example, decarboxylation of the non-psychoactive tetrahydrocannabinolic acid (THCA) produces delta-9-tetrahydrocannabinol (THC) which is psychoactive. Another common cannabinoid acid found in the cannabis plant is cannabidiolic acid (CBDA). The raw form has health – promoting properties, but the step of decarboxylation (to form cannabidiol CBD) makes it more readily available for the body to use, but it remains non-psychoactive. THC has been found to have several therapeutic applications such as treatment of mild to moderate pain, appetite loss, insomnia, depression and nausea. Additionally, THC can be use in the treatment of a variety of autoimmune disorders, including multiple Sclerosiss, colitis, lupus, and arthritis.
CBD has also been found to have several therapeutic benefits including providing relief from chronic pain due to muscle spasticity, muscle convulsions and inflammation. This type of pain is often experienced by patients who suffer from multiple sclerosis, fibromyalgia and epilepsy. In addition to pain relief CBD has been shown to alleviate general feelings of anxiety as well as cannabis-induced anxiety.
Phyto-cannabinoids exist in different forms and produce an equally complex range of effects in the endocannabinoid system. Subtle differences in structure confer differing abilities to stimulate, dampen, or block CB1 and CB2 (or other receptors). For instance, THC stimulates the CB1 and CB2 receptors, while CBD blocks THC from CB1 and weakly dampens CB2. CBD also stimulates certain opioid, dopamine, and serotonin receptors, while preventing the breakdown of Anandamide. As a result, THC primarily relieves pain, increases appetite, decreases nausea, and improves sleep. Due to its multifaceted influence, CBD improves immune function while reducing inflammation, pain, depression, and anxiety.
Recent advancements in selective breeding have enabled Cannabis sativa to yield high concentrations of CBD and low concentrations of THC. CBD concentrations in these hybrid Cannabis sativa L. plants enable CBD yields of 15% and higher and THC yields of 1% and lower.
In an embodiment, the Cannabis sativa leaf extract contains phytocannabinoids in a range of 5% to 40% by weight. In a further embodiment, the Cannabis sativa leaf extract contains phytocannabinoids in a range of 5% to 30% by weight. In a further embodiment, the Cannabis sativa leaf extract contains phytocannabinoids in a range of 5% to 20% by weight. In a further embodiment, the Cannabis sativa leaf extract contains phytocannabinoids in a range of 5% to 10% by weight.
In an embodiment, the Cannabis sativa leaf extract contains phytocannabinoids not less than 5% by weight. In a further embodiment, the Cannabis sativa leaf extract contains phytocannabinoids not less than 10% by weight.
In an embodiment, both THC and CBD create a therapeutic synergistic effect by binding with CB1 and CB2 receptors present on the skin.
As the pain-relieving composition is topical, it only affects the location in which the formulation is applied. As both THC and CBD are lipophilic compounds, when they are absorbed through the skin via topical application, the THC and CBD molecules essentially enter and remain in the adipose cells. As the THC remains in the adipose cell this prevents absorption into the bloodstream and remains at the site where the formulation was applied thereby preventing the user from experience a “THC high” feeling but and improving life quality. The presence of CBD and THC in the formulations reduces inflammation and pain by creating analgesic effect when topically applied. It has been found that the combination of CBD/TCH ingredients creates an immediate as well as a longer lasting pain relief effect.
In an embodiment, the Cannabis sativa leaf extract containing phytocannabinoids is present in the range of 1% to 30% w/w of the total composition. In a further embodiment, the Cannabis sativa leaf extract containing phytocannabinoids is present in the range of 5% to 20% w/w of the total composition. In a further embodiment, the Cannabis sativa leaf extract containing phytocannabinoids is present in the range of 3% to 15% w/w of the total composition.
In an embodiment, the Cannabis sativa leaf extract containing phytocannabinoids (5% to 40% by weight) is present in the range of 1% to 30% w/w of the total composition. In a further embodiment, the Cannabis sativa leaf extract containing phytocannabinoids (5% to 40% by weight) is present in the range of 5% to 20% w/w of the total composition. In a further embodiment, the Cannabis sativa leaf extract containing phytocannabinoids (10% to 30% by weight) is present in the range of 3% to 15% w/w of the total composition.
In an embodiment, the Cannabis sativa leaf extract contains CBD: THC in a ratio of 20:1 or 10:1. In a further embodiment, the Cannabis sativa leaf extract contains CBD: THC in a ratio of 1:1. In a further embodiment, the Cannabis sativa leaf extract contains CBD: THC in a ratio of 1:0.3.
In an embodiment, the Cannabis sativa leaf extract containing phytocannabinoids (5% to 40% by weight) is present in the range of 1% to 30% w/w of the total composition, wherein the leaf extract contains CBD: THC in a ratio of 20:1 or 10:1 or 1:1 or 1:0.3. In a further embodiment, the Cannabis sativa leaf extract containing phytocannabinoids (10% to 30% by weight) is present in the range of 3% to 15% w/w of the total composition, wherein the leaf extract contains CBD: THC in a ratio of 20:1 or 10:1 or 1:1 or 1:0.3.
In an embodiment, TRPA1 antagonist and TRPM8 agonist are present in essential oil of plants including, but not limited to Eucalyptus plant species, including Eucalyptus polybractea, Eucalyptus globulus, Eucalyptus smithii, Eucalyptus radiate, Eucalyptus camaldulensis; Rosmarinus plant species, including Rosmarinus officinalis; and Salvia plant species, including Salvia officinalis, Salvia lavandulifolia.
In an embodiment, TRPA1 antagonist is present in essential oil of plants including Thymus satureioides, Cinnamomum camphora and Cinnamomum burmanni. In some preferred embodiments, the essential oils from different plant species may be mixed as the source of TRPA1 antagonist.
In an embodiment, TRPA1 antagonist is present in essential oil of Eucalyptus globulus. In an embodiment, Eucalyptus essential oil is obtained from Eucalyptus globulus. In another embodiment, Eucalyptus essential oil obtained from Eucalyptus globulus is the source of TRPA1 antagonist and TRPM8 agonist. Further, Eucalyptus oil contains not less than 50% by weight of eucalyptol (C10H18O). Other components typically found in eucalyptus oil include Eucalyptol (54.29%), p-cymene (10.10%), α-pinene (7.78%), β-myrcene (7.78%), γ-terpinene (1.73%) and citronellal (1.62%). Eucalyptus oil has a specific gravity between about 0.905 and 0.925 at 25°C. Eucalyptus oil is preferably obtained by distilling fresh leaves of Eucalyptus globulus. In an embodiment, Eucalyptol, a major component of eucalyptus oil, inhibits TRPA1 channels, and also reduces pain caused by TRPA1 channel agonists applied simultaneously to the skin and additionally stimulates the brain to release endorphins and neurotransmitters. It also modulates the immune response, which can reduce pain, inflammation, and swelling.
In an embodiment, the essential oil of plants comprising TRPA1 antagonist is present in the range of 0.1% to 10% w/w of the total composition. In an embodiment, the essential oil of plants comprising TRPA1 antagonist is present in the range of 0.1% to 8% w/w of the total composition.
In an embodiment, the essential oil of plants selected from Eucalyptus plant species, including Eucalyptus polybractea, Eucalyptus globulus, Eucalyptus smithii, Eucalyptus radiate, Eucalyptus camaldulensis; Rosmarinus plant species, including Rosmarinus Officinalis; Salvia plant species, including Salvia officinalis, Salvia lavandulifolia; and Thymus satureioides, Cinnamomum camphora and Cinnamomum burmanni is present in the range of 0.1% to 10% w/w of the total composition. In an embodiment, the essential oil of Eucalyptus is present in the range of 0.1% to 10% w/w of the total composition.
In an embodiment, the present invention provides a topical pain-relieving composition in which the TRPM8 agonist is menthol, eucalyptol (1,8-cineole), borneol, rotundifolone, linalool, menthone, geraniol, or isopulegol. In an embodiment, the TRPM8 agonist is menthol.
Menthol acts as a counterirritant. Menthol also induces peripheral vasodilation. It is a secondary alcohol extracted from peppermint and can be made synthetically. In suitable amounts, menthol possesses counterirritant properties, producing a feeling of coolness followed by a feeling of warmth. Menthol induces vasodilation, causing the sensation of cold instead of actually cooling of the skin, and the skin temperature at the site is actually warmer than other parts of the body. While menthol activates TRPM8, it may not decrease human inflammatory response, likely because it also activates TRPA1, which causes inflammation. Further, application of menthol with 1,8-cineole significantly reduces irritation through inhibition of TRPA1 by 1,8-cineole.
In some embodiments, the composition of the invention contains menthol crystals which provide a local anesthetic effect with a cool numbing sensation that penetrates the skin. In an embodiment, menthol is natural obtained from essential oils of plants selected from Mentha plant species, including Mentha piperita and Mentha arvensis. In a further embodiment, menthol is synthetic.
In an embodiment, TRPM8 agonist is present in the range of 1% to 10% w/w of the total composition. In a further embodiment, TRPM8 agonist is present in the range of 1% to 8% w/w of the total composition. In an embodiment, menthol is present in the range of 1% to 10% w/w of the total composition.
In an embodiment, COX-2 inhibitor is present in essential oil of plants including, but not limited to Wintergreen plant species including Gaultheria procumbens and sweet birch plant species including Betula lenta. In an embodiment, COX-2 inhibitor is present in essential oil of Wintergreen (Gaultheria procumbens).
Wintergreen oil comprises the following components: Methyl salicylate (85-99%), limonene, α-pinene, sabinene, myrcene, oxygenated monoterpenes, linalool, phenol, vetispirane, and ethyl salicylate. Methyl salicylate is the active ingredient of wintergreen oil (Gaultheria procumbens) obtained from leaves which is a topical counterirritant. Methyl salicylate can be synthesized also and provides symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons.
Methyl salicylate is metabolized in humans to salicylic acid, after absorption through the skin and is therefore also a prodrug to salicylic acid, a known COX-2 inhibitor. Therefore, methyl salicylate can be used as a local topical application of an aspirin-like compound. Further, menthol increases the rate of methyl salicylate absorption through the skin. The action of methyl salicylate is multimodal with analgesic, anti-inflammatory, and rubefacient/counterirritant properties. In an embodiment, topical application of wintergreen leaves essential oil allows penetration through intact skin and absorption of sufficient methyl salicylate to provide pain relief for those suffering with rheumatic conditions, painful muscles, or joints. Further esterases in the skin rapidly hydrolyze salicylate esters to the active salicylic acid in both the epidermis and dermis.
In an embodiment, the essential oil of plants comprising COX-2 inhibitor is present in the range of 1% to 10% w/w of the total composition. In an embodiment, the essential oil of plants comprising COX-2 inhibitor is present in the range of 1% to 8% w/w of the total composition. In an embodiment, the essential oil of Wintergreen is present in the range of 1% to 10% w/w of the total composition.
In an embodiment, the present invention provides a topical pain-relieving composition in which the TRPV1 agonist include, but not limited to capsaicin, resiniferatoxin or hirsuteine.
In an embodiment, capsaicin acts as a counter-irritant. In an embodiment, capsaicin may be obtained from plants of Capsicum genus (family: Solanaceae), also known as chili peppers. Capsaicin (8-methyl N-vanillyl-6-noneamide) is the main pungent principle (capsaicinoid) which act as non-narcotic analgesic and TRPV1 agonist. By acting on the capsaicin receptor or transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1), capsaicin selectively stimulates and in high doses defunctionalizes capsaicin-sensitive chemo-nociceptors with C and Aδ afferent fibers. This channel, which is involved in a wide range of neuronal processes, is expressed in peripheral and central branches of capsaicin-sensitive nociceptive neurons, sensory ganglia, the spinal cord, and different brain regions in neuronal cell bodies, dendrites, astrocytes, and pericytes. Capsaicin may act in the periphery via the vagal sensory fibers expressing TRPV1 receptors to reduce immune oxidative and inflammatory signaling to the brain.
Capsaicin’s pain-relieving mechanism involves a complex interplay of TRPV1 activation, nerve fiber defunctionalization, and reduced pain signal transmission, offering a long-lasting analgesic effect. Capsaicin binds to the TRPV1 receptors which trigger an influx of calcium ions into the nerve cell, causing it to depolarize and send a pain signal to the brain.
After exposure to a high or repeated dose of capsaicin, the TRPV1 receptors begin a refractory state commonly termed as desensitization that leads to inhibition of receptor function. This desensitization is not just a temporary decrease in sensitivity; it involves structural changes in the nerve endings, including the retraction of nerve terminals and altered nerve fiber phenotype. These changes are collectively termed “defunctionalization”. As a result of defunctionalization, nociceptors become less able to transmit pain signals, leading to a reduction in pain perception. This effect can last for a prolonged period, even after capsaicin is no longer being applied. In addition, Capsaicin activates TRPV1, which inhibits Piezo proteins, a family of mammalian cation-selective ion channels that respond to mechanical stretch, and thus provides analgesic effect.
In one embodiment of the present invention, capsaicin is used in a low concentration (0.01% to 1.0% w/w of the total composition) owing to its favorable safety and efficacy profile, characterized by minimal risk of nerve damage or acute overstimulation. Unlike high-concentration capsaicin formulations, the low-dose capsaicin induces gradual desensitization of TRPV1 receptors without causing neurotoxicity or degeneration of epidermal nerve fibers, thereby rendering it suitable for long-term and sustained pain management. Furthermore, the low concentration permits incorporation of capsaicin into multi-component topical formulations, wherein it is synergistically combined with additional analgesic or anti-inflammatory agents such as cannabinoids, Eucalyptus essential oil, menthol, Wintergreen essential oil, and/or Arnica montana oil . These combinations are designed to act via complementary mechanisms, enhancing the overall analgesic efficacy while minimizing the potential for cutaneous irritation or sensitization.
Resiniferatoxin is a diterpene found in plants like Euphorbia resinifera and Euphorbia poissonii. It is a highly potent TRPV1 agonist, even more so than capsaicin. Resiniferatoxin binds to pain receptors in the same way as capsaicin but much more powerfully. Due to its selective nature of binding and killing pain receptors while leaving other nerve cells intact, resiniferatoxin may be used for the treatment of chronic pain.
In an embodiment, hirsuteine may be obtained from plant Uncaria rhynchophylla. Hirsuteine activate and desensitize the TRPV1 channel leading to reduction of pain and inflammation.
In an embodiment, TRPV1 agonist is present in the range of 0.01% to 1.0% w/w of the total composition. In a further embodiment, TRPV1 agonist is present in the range of 0.01% to 0.5% w/w of the total composition. In a further embodiment, Capsaicin is present in the range of 0.01% to 0.5% w/w of the total composition.
A person having ordinary skill in the art would recognize that synthetic sources and plant extracts could be used in this present disclosure as sources of cannabinoids, menthol, 1,8-cineole, borneol, methyl salicylate, capsaicin, resiniferatoxin and hirsuteine instead of natural essential oils.
In an embodiment, the present invention provides a topical pain-relieving composition in which the muscle spasmodic inhibitor includes, but not limited to oil of plants including, but not limited to Arnica plant species, including Arnica montana, Fennel plant species, including Foeniculum vulgare or Ginger plant species, including Zingiber officinale.
In an embodiment, the muscle spasmodic inhibitor is oil of Arnica montana. In an embodiment, the oil is obtained from flower heads of Arnica montana. In an embodiment, the oil obtained from Arnica montana is cold pressed oil. Arnica montana oil comprises essential oil, fatty acids, sesquiterpene lactones, flavone glycosides, thymol, arnicin.
Arnica is claimed to be useful for relieving muscle and joint aches and is frequently cited in herbal literature as being able to promote wound healing. Arnica has also been found to act as an excellent transdermal agent, which is its one of the important uses in the present composition. Arnica’s active ingredients are thought to be flavonoid glycosides and sesquiterpenoid lactones. Arnica can be found in use in the form of spray, gel, cream ointment, tablets, teas, and tinctures. In an embodiment, Arnica oil acts as a transdermal agent that is absorbed quickly and easily into the muscles, ligaments and tendons. Arnica oil, particularly when applied topically, the primary active components sesquiterpene lactones relieves muscle pain through its anti-inflammatory and potentially analgesic (pain-relieving) properties which subsequently alleviates swelling and bruising, which can contribute to pain relief. Specifically, helenalin, a major sesquiterpene lactone, is known to inhibit the NF-κB pathway, which is crucial in regulating inflammation. Additionally, Arnica can reduce the mRNA levels of collagenase-1 (MMP1) and interstitial collagenase-13 (MMP13) in human articular chondrocytes, which are enzymes that play a role in cartilage and joint destruction.
Additionally, Helenalin, 11α,13-dihydrohelenalin, and their respective ester derivatives (e.g., acetate, methacrylate) in the Arnica oil when applied topically, the composition is capable of exerting localized spasmolytic (antispasmodic) effects on underlying smooth and/or skeletal muscle tissues. It modulates the activity of transient receptor potential vanilloid (TRPV1) and acid-sensing ion channels (ASICs) present on peripheral sensory neurons, thereby diminishing neurogenic inflammation and reducing reflexive muscle hyperactivity. Desensitization of nociceptive C-fibers via such modulation contributes to localized muscle relaxation.
Due to their lipophilic structure, sesquiterpene lactones are able to integrate into the phospholipid bilayer of neuronal and muscle cell membranes. This interaction results in reduced membrane excitability and suppression of involuntary contractile activity.
The topical application of Arnica montana oil facilitates improved local blood flow, aiding in the clearance of contractile metabolites such as lactic acid, which otherwise promote muscle stiffness and spasm. Enhanced perfusion contributes to muscle relaxation and overall spasm reduction. These combined mechanisms contribute to the observed therapeutic benefit of the topical formulation, specifically in reducing involuntary or painful muscle contractions (spasms) in localized musculoskeletal conditions.
The active glycosides in Arnica oil bond to the Wintergreen oil and are carried through the skin into the muscles via the sesquiterpenoid lactones in the Arnica oil. In an embodiment, Arnica oil also acts as a penetration enhancer.
Further, it has been surprisingly found that the addition of at least one muscle spasmodic inhibitor, preferably Arnica oil also serves to relax muscles and reduce pain and facilities transport of topical pain relieving composition of cannabinoids, essential oil of plants comprising TRPA1 antagonists such as Eucalyptus essential oil, menthol, wintergreen oil, TRPV1 agonist such as capsaicin, resiniferatoxin or hirsuteine, through and into the dermis, epidermis, subcutis and to tissues below the skin.
In an embodiment, muscle spasmodic inhibitor is present in the range of 1% to 40% w/w of the total composition. In an embodiment, muscle spasmodic inhibitor is present in the range of 5% to 15% w/w of the total composition. In an embodiment, oil of Arnica montana, Foeniculum vulgare or Zingiber officinale is present in the range of 1% to 40% w/w of the total composition. In an embodiment, Arnica montana oil is present in the range of 5% to 15% w/w of the total composition.
In an embodiment, the topical pain-relieving composition optionally comprises a a topically active non-steroidal anti-inflammatory agent (NSAID) including but not limited to benzydamine, indomethacin, arthrotec, celecoxib, diclofenac, rofecoxib, vadecoxib, naproxen, ibuprofen, piroxicam, ketoprofen, felbinac, or combination thereof. In an embodiment, the NSAID is diclofenac or a salt of diclofenac.
In an embodiment, the pain-relieving composition comprising NSAIDs in combination with a cannabinoid, a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist and a COX-2 inhibitor is unexpectedly effective in pain relief and reduction of inflammation.
In an embodiment, the pain-relieving composition comprising NSAIDs in combination with a cannabinoid, a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist, a COX-2 inhibitor and muscle spasmodic inhibitor is unexpectedly effective in pain relief and relaxation of muscles.
In an embodiment, the pain-relieving composition comprises a therapeutically effective amount of a NSAID. A topically active NSAID means a NSAID when used in combination with a suitable carrier can be transported through the skin barrier of mammals and becomes locally active in and below the skin and is safe for exposure to skin without unacceptable reactions.
In an embodiment, the topical pain-relieving composition further comprises at least one pharmaceutically acceptable carrier. In an embodiment, the carrier is an oil. In an embodiment, the carrier includes but not limited to grape seed oil, medium-chain triglycerides oil, olive oil, coconut oil, sesame oil, jojoba oil, rosehip oil, palm oil, flaxseed oil, hemp seed oil, chamomile oil, cinnamon oil, citron oil, nutmeg oil, oregano oil, orris oil, palo santo oil, parsley oil, peppermint oil or any combination thereof.
In an embodiment, the carrier also acts as a penetration enhancer. In an embodiment, an effective amount of a carrier as a penetration enhancer may be incorporated into the pain-relieving composition to aid penetration of the active ingredients.
Fractionated coconut oil is a purified form of coconut oil that contains only its medium-chain triglycerides (MCTs), resulting in a liquid and highly stable oil. It is produced by first hydrolyzing coconut oil to release its fatty acids, followed by steam distillation to selectively isolate the MCT fraction. MCTs contain a mixture of fatty acids of 6-12 carbon saturated fatty acids composed mainly of caprylic-C8:0 (80%), capric-C10:0 (20%-50%), caproic-C6:0, and lauric acid-C12:0 (1%-2%, respectively). Fractionated coconut oil has indefinite shelf life and is a light, non-greasy, non-staining, liquid oil. It is a very good choice for use with essential oils, as it helps carry therapeutic oils under the skin.
In an embodiment, the carrier is medium-chain triglycerides (MCT) oil obtained from coconut oil. In an embodiment, the carrier is medium-chain triglycerides (MCT) oil obtained from coconut oil or coconut oil in combination with grape seed oil, medium-chain triglycerides oil, olive oil, sesame oil, jojoba oil, rosehip oil, palm oil, flaxseed oil, hemp seed oil, chamomile oil, cinnamon oil, citron oil, nutmeg oil, oregano oil, orris oil, palo santo oil, parsley oil, and/or peppermint oil.
In an embodiment, the carrier is present in the range of 1% to 90% w/w of the total composition. In a further embodiment, the carrier is present in the range of 10% to 90% w/w of the total composition. In an embodiment, medium-chain triglycerides (MCT) oil is present in the range of 1% to 90% w/w of the total composition. In a further embodiment, medium-chain triglycerides (MCT) oil is present in the range of 10% to 90% w/w of the total composition. In a further embodiment, medium-chain triglycerides (MCT) oil obtained from coconut oil is present in the range of 1% to 90% w/w of the total composition.
In an embodiment, the pain-relieving composition may be delivered in the form of an oil, cream, lotion, ointment, paste, gel, suspension, pump spray, aerosol spray, non-pressurized spray, continuous spray, non-chloro fluorocarbon-based spray, aerosol foam, liquid, solution, powder, stick, roll -on or patch, preferably oil.
In an embodiment, the pain-relieving composition may comprise pharmaceutically acceptable excipients. In an embodiment, the pharmaceutically acceptable excipients used in the compositions of the present invention comprises thickener, emollient, humectant, surfactant, preservative or anti-microbials and stabilizers such as polyols, salts and/or esters of carboxylic acid, steric acid or a combination thereof; Vitamins such as Vitamin A, E or Vitamin D; Surfactants belonging to anionic, cationic and/or non-ionic groups; antioxidants such as lipoic acid and the like, structure-forming ingredients, anti-microbial agents such as para chloro meta cresol, phenoxyethanol, potassium sorbate, sodium benzoate, paraben and the like, antibiotic agents, and/or anesthetic agents.
In an embodiment, an effective amount of a thickener may be incorporated within the formulation to obtain the desired viscosity and consistency of the product for example, as use as a cream, lotion or ointment.
In an embodiment, excipients ares present in the range of about 0.01% to about 50% w/w of the total composition. In an embodiment, excipients ares present in the range of about 0.01% to about 30% w/w of the total composition. In an embodiment, excipients ares present in the range of about 0.01% to about 10% w/w of the total composition.
In an embodiment, the present invention provides a process for preparing the composition of the present invention.
In an embodiment, one of the process for preparing the composition of present invention comprises the following steps:
Step 1: Charging carrier oil into the stainless-steel preparation vessel and stirring.
Step 2: Adding Cannabis plant extract into the vessel and stirring for mixing.
Step 3: Adding COX-2 inhibitor comprising essential oil of plants selected from Wintergreen (Gaultheria procumbens) or sweet birch (Betula lenta) into the preparation vessel under stirring, which is further stirred for mixing.
Step 4: Adding muscle spasmodic inhibitor including an oil of Arnica montana, Foeniculum vulgare or Zingiber officinale into the preparation vessel under stirring, which is further stirred for mixing.
Step 5: Adding TRPM8 agonist selected from menthol, eucalyptol, borneol, rotundifolone, linalool, menthone, geraniol, isopulegol or a combination thereof, into the above oil mixture of step 4 under stirring, which is further stirred to dissolve it completely.
Step 6: Adding TRPV1 agonist selected from capsaicin, resiniferatoxin or hirsuteine into the preparation vessel under stirring, which is further stirred to dissolve it completely.
Step 7: Finally, adding TRPA1 antagonist comprising essential oil of plants selected from Eucalyptus species comprising Eucalyptus polybractea, Eucalyptus globulus, Eucalyptus smithii, Eucalyptus radiate or Eucalyptus camaldulensis; Rosmarinus species comprising Rosmarinus officinalis; Salvia species comprising Salvia officinalis or Salvia lavandulifolia; Thymus satureioides; Cinnamomum camphora or Cinnamomum burmanni to the oil mixture of step 6 while stirring.
Step 8: Transferring the entire mixture to a stainless-steel homogenization vessel and homogenizing by mechanical agitation to ensure uniform distribution of all actives.
Step 9: Filtering the homogenized product of Step 8 and using the filtrate obtained for further analysis.
In an embodiment, the above process of preparation may be applied for preparation of different compositions, provided that the ingredients are added according to a particular composition.
In an embodiment, the topical pain-relieving composition comprises at least one phyto-cannabinoid; at least one natural analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof.
In an embodiment, the present invention provides a topical pain-relieving composition comprising Cannabis plant extract, Eucalyptus essential oil, menthol, Wintergreen essential oil and Capsaicin.
In an embodiment, the topical pain-relieving composition comprises at least one phyto-cannabinoid; at least one natural analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof; and at least one muscle spasmodic inhibitor.
In an embodiment, the present invention provides a topical pain-relieving composition comprising Cannabis plant extract, Eucalyptus essential oil, menthol, Wintergreen essential oil, Capsaicin and Arnica montana oil.
In an embodiment, the topical pain-relieving composition comprises at least one phyto-cannabinoid; at least one natural analgesic and/or anti-inflammatory agent selected from a TRPM8 agonist, a TRPA1 antagonist, a TRPV1 agonist or COX-2 inhibitor or a combination thereof; at least one muscle spasmodic inhibitor; and a carrier.
In an embodiment, the present invention provides a topical pain-relieving composition comprising Cannabis plant extract, Eucalyptus essential oil, menthol, Wintergreen essential oil, Capsaicin and medium-chain triglycerides (MCT) from coconut oil.
In an embodiment, the present invention provides a topical pain-relieving composition comprising Cannabis plant extract, Eucalyptus essential oil, menthol, Wintergreen essential oil, Capsaicin, Arnica montana oil and medium-chain triglycerides (MCT) from coconut oil.
In an embodiment, the topical pain-relieving composition of the present invention may be used to reduce pain and inflammation associated with one or more of nociceptive, neuropathic, somatic pain, radicular pain and associated musculoskeletal, osteoarthritic, muscle, joint, arthritis, rheumatoid arthritis, back, strains and sprains pain associated with sports injuries, post – surgical conditions and other diseases. In an embodiment, the topical compositions may also be used to treat pain associated with pre-surgical and post-surgical orthopedic procedures.
In an embodiment, the topical compositions may also be used to treat pain associated with muscle spasms, hematomas, bruises, sprains, muscle spasms, partial tendon, tears, tendonitis, bursitis, myositis; neuralgia; and pain caused by other diseases, disorders or conditions.
As used herein, “arthritis” refers to inflammation of the bone fascia producing pain and immobility. “Joint inflammation” refers to an inflammatory response occurring in the bone joints, producing pain and immobility.” Joint pain” refers to pain associated with the relative motion of two or more bones at a mutual joint thereof. “Neuropathic pain and spasticity” refer to pain and loss of muscle control produced by damage or disease that affects the somatosensory system, which can result from injury or disease of the central or peripheral nervous systems.
The present invention further comprises following embodiments:
(A1) A topical pain relief formulation comprising:
a) Phyto-cannabinoids comprising combination of two or more cannabinoids,
b) topical counter-irritant (Essential oil)
c) Synthetic topical counter-irritant
d) TRPV1 agonist
e) Analgesic and anti-inflammatory agent (Essential oil)
f) Cold pressed oil-Muscle spasmodic inhibitor, which reduces ecchymosis (bruising)
g) Carrier oil and transdermal enhancer
(A2) The topical pain relief formulation according to (A1), wherein the two or more cannabinoids are selected from the group of phyto cannabinoids consisting of: tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), Cannabigerolic acid monomethyl ether (CBGM), cannabielsoin (CBE) and cannabicitran (CBT).
(A3) The topical pain relief formulation according to (A2), wherein the ratio of CBD and THC in the phyto-cannabinoids is 1:0.3.
(A4) The topical pain relief formulation according to (A1) and (A2), wherein the formulation comprises from about 10% to about 30% of Phyto-cannabinoids in Cannabis sativus leaves extract, preferably 20%.
(A5) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 5% to about 15% of Cannabis sativus leaves extract, most preferably 10%.
(A6) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 3% to about 7% of Wintergreen essential oil as essential oil topical counter-irritant, most preferably 5%.
(A7) The topical pain relief formulation according to (A1) and (A2), wherein the formulation comprises from about 85% to about 95% of methyl salicylate in Wintergreen essential oil, most preferably 90%.
(A8) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 5% to about 15% of Arnica montana flower cold pressed oil as muscle spasmodic inhibitor, most preferably 10%.
(A9) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 3% to about 7% of menthol as synthetic topical counter-irritant, most preferably 5%.
(A10) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 0.03% to about 0.09% of capsaicin as TRPV1 agonist, most preferably 0.06%.
(A11) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 1% to about 7% of eucalyptus essential oil, most preferably 4%.
(A12) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 0.1% to about 0.5% of eucalyptus essential oil as essential oil analgesic and anti-inflammatory agent, most preferably 0.3%.
(A13) The topical pain relief formulation according to (A1), wherein the formulation comprises from about 50% to about 90% of MCT oil as carrier oil, most preferably 65.97%.
(A14) According to the various embodiments of the invention, the topical formulation of (A1) may be in the form of an oil, cream, lotion, ointment, paste, gel, suspension, pump spray, aerosol spray, non-pressurized spray, continuous spray, non-chloro fluorocarbon – based spray, aerosol foam, liquid, solution, powder, stick, roll -on or patch, most preferably oil.
(A15) The topical pain relief formulation according to (A1), wherein the pain is selected from the group consisting of: Arthritis pain, neck pain, shoulder pain, back pain, bone injury pain, muscle pain, pain associated with muscle tension, fatigue, curvature of spine, major and minor spinal disc compression, pinched nerves, strained or sprained muscles, nervous tension, delayed onset muscle soreness (DOMS), pain associated with muscle spasms, pain caused by sports related injuries, partial tendon tears, tendonitis, myositis, neuralgia, pain caused by slipped disc, joint dislocations, whiplash injury, pain associated with pre-surgical and post-surgical orthopedic procedures, spinal stenosis, traumatic bone fracture, Bursitis and pain caused by other diseases, disorders or conditions.
(A16) The topical pain relief oil formulation according to any of (A1) to (A15), wherein the subject is human being.
Embodiments are further defined in the following examples. The following experiments are provided to exemplarily illustrate various aspects of the inventive subject matter presented herein. However, it should be apparent to those skilled in the art that many more modifications besides those already described are possible without departing from the inventive concepts herein. The following examples are for the purpose of illustration of the invention and are not intended in any way to limit the scope of the invention.
EXAMPLES
Example 1: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (not less than 10% phytocannabinoids) 10
2 Medium-chain triglycerides (MCT oil) from coconut oil
80
3 Camphor 5
4 Eucalyptus essential oil 5

Example 2: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (not less than 10% phytocannabinoids) 5
2 Medium-chain triglycerides (MCT oil) from coconut oil 84
3 Diclofenac sodium 1
4 Eucalyptus essential oil 5
5 Menthol 5

Example 3: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (not less than 10% phytocannabinoids) 5
2 Hemp seed oil 69.9
3 Arnica montana flower cold pressed oil 10
4 Menthol 5
5 Wintergreen essential oil (not less than 70% methyl salicylate) 5
6 Eucalyptus essential oil 5
7 Capsaicin 0.1

Example 4: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (not less than 10% phytocannabinoids) 3
2 Coconut oil 90
3 Mentha arvensis extract 2
4 Eucalyptus essential oil 5

Example 5: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (not less than 10% phytocannabinoids) 10
2 Medium-chain triglycerides (MCT) from coconut oil 69.9
3 Wintergreen essential oil (not less than 70% methyl salicylate) 5
4 Arnica montana flower cold pressed oil 10
5 Menthol 5
6 Capsaicin 0.1

Example 6: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (15-20% phytocannabinoids) 10
2 Medium-chain triglycerides (MCT oil) from coconut oil 69.64
3 Wintergreen Essential oil (not less than 70% methyl salicylate) 5
4 Arnica montana flower cold pressed oil 10
5 Menthol 5
6 Capsaicin 0.06
7 Eucalyptus essential oil 0.3

Example 7: Pain relieving composition.
Sl. No Ingredients % (w/w)
1 Cannabis sativa leaf extract (15-20% phytocannabinoids) 10
2 Medium-chain triglycerides (MCT oil) from coconut oil 65.97
3 Wintergreen Essential oil (not less than 70% methyl salicylate) 5
4 Arnica montana flower cold pressed oil 10
5 Menthol 5
6 Capsaicin 0.03
7 Eucalyptus essential oil 4

Process of preparation: The process for preparation of the pain relieving composition comprises the steps as below.
Step 1: 65.97 Kg of MCT Oil from coconut oil was charged into the clean and dried stainless-steel preparation vessel and stirred at 40 RPM for about 10 minutes.
Step 2: 10 Kg of Cannabis sativa leaf extract (15-20% phyto-cannabinoids) was added into the stainless-steel preparation vessel and stirred at 60 RPM for about 90 minutes.
Step 3: 5 Kg of Wintergreen essential oil (not less than 70% methyl salicylate) was added into the preparation vessel under stirring and further stirred for about 90 minutes at 30 RPM.
Step 4: 10 Kg of Arnica montana oil was added into the preparation vessel under stirring and further stirred for about 30 minutes at 60 RPM.
Step 5: 5 Kg of menthol was added into the above oil mixture of step 4 under stirring and further stirred for about 30 minutes at 60 RPM to dissolve it completely.
Step 6: 30 g of Capsaicin was added into the preparation vessel under stirring and further stirred for about 30 minutes at 80 RPM to dissolve it completely.
Step 7: Finally, 4 Kg of Eucalyptus essential oil was added to the oil mixture of step 6 while stirring for about 30 minutes at 80 RPM.
Step 8: The entire mixture was transferred to a clean and dried stainless-steel homogenization vessel and homogenized by mechanical agitation for about 10 minutes at 80 RPM to ensure uniform distribution of all actives.
Step 9: The homogenized material of step 8 is filtered through 0.5 µm nylon filter cloth and the filtrate obtained is used for further analysis.
The above process of preparation applies for other examples also, provided that the ingredients are added according to the compositions of the examples.

Examples 8, 9, 10, 11, 12: Pain relieving composition.
Ingredients % (w/w)
Example 8 Example 9 Example 10 Example 11 Example 12
Cannabis sativa leaf extract (not less than 15-20% phytocannabinoids (CBD: THC (1:0.05)] 10 10 - - -
Cannabis sativa leaf extract (not less than 15-20% phytocannabinoids (CBD: THC (1:0.3)] - - 10 10 10
Eucalyptus essential oil - 4 0.3 4 4
Menthol 5 5 - - 5
Mentha arvensis extract - - 5 5 -
Wintergreen essential oil (not less than 70% methyl salicylate) 5 4.97 5 5 5
Capsaicin 0.06 0.03 0.06 0.03 -
Arnica montana flower oil 10 10 10 10 10
Medium-chain triglycerides (MCT) from coconut oil 69.64 65.7 69.64 65.97 65.7
Preservative
Tocopherol (Vitamin E) 0.3 0.3 - - 0.3

EXAMPLES - BIOLOGICAL
Twenty-five persons (both gender) suffering from different kind of pain were provided with 20 mL sample of pain relief composition prepared according to example 1 to example 7. The formulation along with a questionnaire was given to the person for continuous use of the product for at least one week. This questionnaire assesses the nature, intensity, and pattern of a person's pain before and after applying the cannabis-based topical composition of the present invention, including the type of pain, its location, and any ongoing treatments. It also evaluates the relief experienced using a numerical pain scale and subjective feedback (e.g., warmth, stickiness, duration of relief).
Additionally, it includes an Activity Tolerance Scale (ATS) to measure the patient's ability to perform daily activities despite pain, helping to determine functional improvement after oil application. The Activity Tolerance Scale is a pain intensity scale often used in clinical settings to assess how much pain a patient is experiencing and how it impacts their ability to carry out physical activity. Hence, it helps to monitor treatment progress (e.g., before and after applying a topical analgesic), quantify how pain interferes with function and measure reduction in pain over time or after intervention. The scale ranges from 0 to 10, representing increasing levels of discomfort or pain. The score breakdown for the pain assessment is given in table 1.

Table 1: Activity Tolerance Scale for Pain Assessment.
Score Description Interpretation
0 No Pain Fully active, no limitation
1–3 Mild Pain Can perform activities with minimal discomfort
4–6 Moderate Pain Activity is affected; may need rest or reduced exertion
7–9 Severe to Very Severe Pain Significantly limits activity; rest required
10 Worst Pain Possible Completely intolerable, unable to perform any activity

Average percentage of pain reduction can be calculated by the following formula:

Average percentage pain reduction = (Score before -Score after) × 100
Score before

Score before = Score before applying the composition
Score after = Score after applying the composition
RESULTS
All identified users were periodically monitored for follow-up regarding the actual usage of the product. Data analysis indicated that 100% of users reported being satisfied or extremely satisfied with the product’s performance. Most participants experienced noticeable pain relief within 5 to 10 minutes of application, particularly for conditions such as arthritis, muscle soreness, sprain, and neuropathy. A significant majority (70.12%) reported that the product absorbed quickly without leaving a greasy residue. Furthermore, 80.65% of respondents felt the product was better or much better compared to other topical pain relief products available in the market. The remaining 19.35% rated it on par with existing products. Notably, none of the users considered the product to be inferior to other market formulations.
The average percentage pain reduction after applying the composition of Examples 1 to 7 is shown in the table 2.
Table 2: Average percentage pain reduction for various topical compositions.
Composition Average Percentage Pain Reduction (%)
Example 1 63.21± 0.89
Example 2 75.40± 1.46
Example 3 74.38± 1.73
Example 4 68.54± 0.97
Example 5 78.13± 1.51
Example 6 80.69± 1.34
Example 7 85.26± 1.02

Table 3: Activity Tolerance Score before and after applying the composition of Example 7.
Participants Activity Tolerance Score % Pain Reduction
Before Application of the composition After Application of the composition
1 7 1 85.71
2 10 1 90.00
3 8 1 87.50
4 7 1 85.71
5 8 2 75.00
6 6 1 83.33
7 8 1 87.50
8 6 1 83.33
9 7 1 80.03
10 6 1 83.33
11 6 1 83.33
12 7 1 85.71
13 6 1 83.33
14 9 1 88.89
15 8 1 87.50
16 9 1 88.89
17 6 1 83.33
18 7 1 85.71
19 9 1 88.89
20 7 1 85.71
21 8 1 87.50
22 9 1 88.89
23 6 1 83.33
24 7 1 85.71
25 6 1 83.33
Average Percentage Pain reduction (%) 85.26

Observations: Among the compositions of Examples 1 to 7, composition of Example 7 showed the highest mean reduction in pain at 85.23 ± 1.02%, followed by composition of Example 6 (80.69 ± 1.34%) and composition of Example 5 (78.13 ± 1.51%). The lowest average reduction was observed with composition of Example 1 (63.21 ± 0.89%). These findings suggest that the compositions, particularly of Examples 5 to 7, provide substantial pain relief and improved activity tolerance, indicating their potential efficacy as topical analgesics.
Modifications to embodiments of the present disclosure described above are possible without deviating from the spirit and the scope of the disclosure. The foregoing embodiments are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention. , Claims:1. A topical pain-relieving composition comprising:
a) at least one cannabinoid;
b) natural analgesic agents selected from TRPM8 agonists, TRPA1 antagonists, TRPV1 agonists, COX-2 inhibitors or combination thereof; and
c) at least one muscle spasmodic inhibitor.

2. The topical pain-relieving composition as claimed in claim 1, wherein the cannabinoid comprises two or more phyto-cannabinoids present in the extract of Cannabis plant selected from Cannabis sativa, Cannabis indica or Cannabis ruderalis.

3. The topical pain relieving composition as claimed in claim 2, wherein phyto-cannabinoids are selected from tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), Cannabigerolic acid monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT) or a combination thereof.

4. The topical pain-relieving composition as claimed in claim 1, wherein the composition comprises one or more carriers.

5. The topical pain-relieving composition as claimed in claim 1 to 4, wherein the composition comprises:
h) 1% to 30% w/w of Cannabis plant extract;
i) 0.1% to 10% w/w of TRPA1 antagonist;
j) 1% to 10% w/w of TRPM8 agonist;
k) 1% to 10% w/w of COX-2 inhibitor;
l) 0.01% to 1.0% w/w of TRPV1 agonist;
m) 1% to 40% w/w of muscle spasmodic inhibitor; and
n) 1% to 90% w/w of carrier.

6. The topical pain-relieving composition as claimed in claim 1 or 5, wherein TRPA1 antagonist comprises essential oil of plants selected from Eucalyptus species comprising Eucalyptus polybractea, Eucalyptus globulus, Eucalyptus smithii, Eucalyptus radiate or Eucalyptus camaldulensis; Rosmarinus species comprising Rosmarinus officinalis; Salvia species comprising Salvia officinalis or Salvia lavandulifolia; Thymus satureioides; Cinnamomum camphora or Cinnamomum burmanni.

7. The topical pain relieving composition as claimed in claim 1 or 5, wherein TRPM8 agonist is selected from menthol, eucalyptol, borneol, rotundifolone, linalool, menthone, geraniol, isopulegol or a combination thereof.

8. The topical pain relieving composition as claimed in claim 1 or 5, wherein COX-2 inhibitor comprises essential oil of plants selected from Wintergreen (Gaultheria procumbens) or sweet birch (Betula lenta).

9. The topical pain-relieving composition as claimed in claim 1, wherein TRPV1 agonist is selected from capsaicin, resiniferatoxin or hirsuteine.

10. The topical pain relieving composition as claimed in claim 1 or 5, wherein the muscle spasmodic inhibitor is selected from an oil of Arnica montana, Foeniculum vulgare or Zingiber officinale.

11. The topical pain-relieving composition as claimed in claim 1 or 5, wherein the composition optionally comprises a non-steroidal anti-inflammatory agent selected from benzydamine, indomethacin, arthrotec, celecoxib, diclofenac, rofecoxib, vadecoxib, naproxen, ibuprofen, piroxicam, ketoprofen, felbinac, or a combination thereof.

12. The topical pain relieving composition as claimed in claim 4 or 5, wherein the carrier is an oil selected from the group consisting of grape seed oil, medium-chain triglycerides oil, olive oil, coconut oil, sesame oil, jojoba oil, rosehip oil, palm oil, flaxseed oil, hemp seed oil, chamomile oil, cinnamon oil, citron oil, nutmeg oil, oregano oil, orris oil, palo santo oil, parsley oil, peppermint oil or a combination thereof.

13. The topical pain-relieving composition as claimed in any of the preceding claims, wherein the composition comprises:
a) 1% to 30% w/w of Cannabis plant extract;
b) 0.1% to 10% w/w of essential oil of plants selected from Eucalyptus, Rosmarinus, Salvia, Thymus satureioides, Cinnamomum camphora or Cinnamomum burmanni;
c) 1% to 10% w/w of menthol, eucalyptol, borneol, rotundifolone, linalool, menthone, geraniol, isopulegol or a combination thereof;
d) 1% to 10% w/w essential oil of plants selected from Wintergreen (Gaultheria procumbens) or sweet birch (Betula lenta);
e) 0.01% to 1.0% w/w of capsaicin, resiniferatoxin or hirsuteine;
f) 1% to 40% w/w of oil of plants selected from Arnica (Arnica montana), Fennel (Foeniculum vulgare) or Ginger (Zingiber officinale); and
g) 1% to 90% w/w of carrier selected from the group consisting of grape seed oil, medium-chain triglycerides oil, olive oil, coconut oil, sesame oil, jojoba oil, rosehip oil, palm oil, flaxseed oil, hemp seed oil, chamomile oil, cinnamon oil, citron oil, nutmeg oil, oregano oil, orris oil, palo santo oil, parsley oil, peppermint oil or a combination thereof.

14. The topical pain-relieving composition as claimed in any of the preceding claims, wherein composition is in the form of an oil, cream, lotion, ointment, paste, gel, suspension, spray, pump spray, aerosol spray, non-pressurized spray, continuous spray, aerosol foam, liquid, mousse or solution.